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TY  - INPR
ID  - 2505
TI  - Domestication has altered gene expression and secondary metabolites in pea seed coat
JO  - Plant J.
PY  - 2024
SP  - 
AU  - Klčová, B.
AU  - Balarynová, J.
AU  - Trněný, O.
AU  - Krejčí, P.
AU  - Cechová, M. Z.
AU  - Leonova, T.
AU  - Gorbach, D.
AU  - Frolova, N.
AU  - Kysil, E.
AU  - Orlova, A.
AU  - Ihling, ?.
AU  - Frolov, A.
AU  - Bednář, P.
AU  - Smýkal, P.
AU  - 
VL  - 
UR  - https://doi.org/10.1111/tpj.16734
DO  - 10.1111/tpj.16734
AB  - The mature seed in legumes consists of an embryo and seed coat. In contrast to knowledge about the embryo, we know relatively little about the seed coat. We analyzed the gene expression during seed development using a panel of cultivated and wild pea genotypes. Gene co‐expression analysis identified gene modules related to seed development, dormancy, and domestication. Oxidoreductase genes were found to be important components of developmental and domestication processes. Proteomic and metabolomic analysis revealed that domestication favored proteins involved in photosynthesis and protein metabolism at the expense of seed defense. Seed coats of wild peas were rich in cell wall‐bound metabolites and the protective compounds predominated in their seed coats. Altogether, we have shown that domestication altered pea seed development and modified (mostly reduced) the transcripts along with the protein and metabolite composition of the seed coat, especially the content of the compounds involved in defense. We investigated dynamic profiles of selected identified phenolic and flavonoid metabolites across seed development. These compounds usually deteriorated the palatability and processing of the seeds. Our findings further provide resources to study secondary metabolism and strategies for improving the quality of legume seeds which comprise an important part of the human protein diet.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - INPR
ID  - 2500
TI  - Acrylate‐derived RAFT polymers for enzyme hyperactivation – boosting the α‐chymotrypsin enzyme activity using tailor‐made poly(2‐carboxyethyl)acrylate (PCEA)
JO  - ChemCatChem
PY  - 2024
SP  - 
AU  - Müllers, Y.
AU  - Sadr, A. S.
AU  - Schenderlein, M.
AU  - Pallab, N.
AU  - D. Davari, M.
AU  - Glebe, U.
AU  - Reifarth, M.
AU  - 
VL  - 
UR  - https://doi.org/10.1002/cctc.202301685
DO  - 10.1002/cctc.202301685
AB  - We study the hyperactivation of α‐chymotrypsin (α‐ChT) using the acrylate polymer poly(2‐carboxyethyl) acrylate (PCEA) in comparison to the commonly used poly(acrylic acid) (PAA). The polymers are added during the enzymatic cleavage reaction of the substrate N‐glutaryl‐L‐phenylalanine p‐nitroanilide (GPNA). Enzyme activity assays reveal a pronounced enzyme hyperactivation capacity of PCEA, which reaches up to 950% activity enhancement, and is significantly superior to PAA (revealing an activity enhancement of approx. 450%). In a combined experimental and computational study, we investigate α‐ChT/polymer interactions to elucidate the hyperactivation mechanism of the enzyme. Isothermal titration calorimetry reveals a pronounced complexation between the polymer and the enzyme. Docking simulations reveal that binding of polymers significantly improves the binding affinity of GPNA to α‐ChT. Notably, a higher binding affinity is found for the α‐ChT/PCEA compared to the α‐ChT/PAA complex. Further molecular dynamics (MD) simulations reveal changes in the size of the active site in the enzyme/polymer complexes, with PCEA inducing a more pronounced alteration compared to PAA, facilitating an easier access for the substrate to the active site of α‐ChT.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 213
TI  - Thermal degradation of (2R, 3R)-dihydromyricetin in neutral aqueous solution at 100 ℃
JO  - Food Chem.
PY  - 2024
SP  - 137560
AU  - Zhang, H.
AU  - Lin, S.
AU  - Xie, R.
AU  - Zhong, W.
AU  - Wang, H.
AU  - Farag, M. A.
AU  - Hussain, H.
AU  - Arroo, R. R.
AU  - Chen, X.
AU  - Xiao, J.
AU  - 
VL  - 435
UR  - https://doi.org/10.1016/j.foodchem.2023.137560
DO  - 10.1016/j.foodchem.2023.137560
AB  - In the field of thermal degradation of flavonoids, current studies mainly focused on flavonols. However, the thermal degradation of dihydroflavonols in aqueous solution has received limited attention compared to flavonols. The single C2-C3 bonds of dihydroflavonols, which differs from the C2-C3 double bond in flavonols, may cause different degradation mechanisms. Dihydromyricetin (DMY) is a typical dihydroflavonol with six hydroxyl groups, and possesses various health effects. We explored the thermal degradation of DMY in neutral aqueous solution (pH 7) at 100 ℃. Ultra-performance liquid chromatography combined with photodiode array and electrospray ionization quadrupole-time-of-flight tandem mass spectrometric detection (UPLC-PDA-ESI-QTOF-MS/MS) provided suitable platform for exploring DMY degradation pathways, and negative ion mode was applied. Thermal treatment led to a decline in DMY level with time, accompanied by the appearance of various degradation products of DMY. Degradation mechanisms of DMY included isomerization, oxidation, hydroxylation, dimerization and ring cleavage. The pyrogallol-type ring B of DMY might be initially oxidized into ortho-quinone, which could further attack another DMY to form dimers. In addition, hydroxylation is likely to occur at C-2, C-3 of DMY or DMY dimers, which then further yields ring-cleavage products via breakage of the O1-C2 bond, C2-C3 bond, or C3-C4 bond. The 3-hydroxy-5-(3,3,5,7-tetrahydroxy-4-oxochroman-2-yl) cyclohexa-3,5-diene-1, 2-dione (m/z 333.0244) and unknown compound m/z 435.0925 were annotated as key intermediates in DMY degradation. Four phenolic acids, including 3,4,5-trihydroxybenzoic acid (m/z 169.0136, RT 1.4 min), 2,4,6-trihydroxyphenylglyoxylic acid (m/z 197.0084, RT 1.7 min), 2-oxo-2-(2,4,6-trihydroxyphenyl) acetaldehyde (m/z 181.0132, RT 2.4 min), and 2,4,6-trihydroxybenzoic acid (m/z 169.0139, RT 2.5 min) were identified as the major end products of DMY degradation. In addition, 5-((3,5dihydroxyphenoxy) methyl)-3-hydroxycyclohexa-3,5-diene-1,2-dione (m/z 261.0399, RT 11.7 min) and unidentified compound with m/z 329.0507 (RT 1.0 min) were also suggested to be end products of DMY degradation. These results provide novel insights on DMY stability and degradation products. Moreover, the heat treatment of DMY aqueous solution was found to gradually reduce the antioxidant activities of DMY, and even destroy the beneficial effect of DMY on the gut microbiota composition.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 211
TI  - Chemoenzymatic synthesis of a new germacrene derivative named germacrene F
JO  - ChemBioChem
PY  - 2024
SP  - e202300599
AU  - Struwe, H.
AU  - Droste, J.
AU  - Dhar, D.
AU  - Davari, M. D.
AU  - Kirschning, A.
AU  - 
VL  - 25
UR  - https://doi.org/10.1002/cbic.202300599
DO  - 10.1002/cbic.202300599
AB  - The new farnesyl pyrophosphate (FPP) derivative with a shifted olefinic double bond from C6‐C7 to C7‐C8 is accepted and converted by the sesquiterpene cyclases protoilludene synthase (Omp7) as well as viridiflorene synthase (Tps32). In both cases, a so far unknown germacrene derivative was found to be formed, which we name “germacrene F”. Both cases are examples in which a modification around the central olefinic double bond in FPP leads to a change in the mode of initial cyclization (from 1→11 to 1→10). For Omp7 a rationale for this behaviour was found by carrying out molecular docking studies. Temperature‐dependent NMR experiments, accompanied by NOE studies, show that germacrene F adopts a preferred mirror‐symmetric conformation with both methyl groups oriented in the same directions in the cyclodecane ring.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 208
TI  - A multiplex approach of MS, 1D‐, and 2D‐NMR metabolomics in plant ontogeny: A case study on Clusia minor L. organs (leaf, flower, fruit, and seed)
JO  - Phytochem. Anal.
PY  - 2024
SP  - 445-468
AU  - Noleto‐Dias, C.
AU  - Farag, M. A.
AU  - Porzel, A.
AU  - Tavares, J. F.
AU  - Wessjohann, L. A.
AU  - 
VL  - 35
UR  - https://doi.org/10.1002/pca.3300
DO  - 10.1002/pca.3300
AB  - Introduction: The genus Clusia L. is mostly recognised for the production of prenylated benzophenones and tocotrienol derivatives.Objectives: The objective of this study was to map metabolome variation within Clusia minor organs at different developmental stages.Material and Methods: In total 15 organs/stages (leaf, flower, fruit, and seed) were analysed by UPLC‐MS and 1H‐ and heteronuclear multiple‐bond correlation (HMBC)‐NMR‐based metabolomics.Results: This work led to the assignment of 46 metabolites, belonging to organic acids(1), sugars(2) phenolic acids(1), flavonoids(3) prenylated xanthones(1) benzophenones(4) and tocotrienols(2). Multivariate data analyses explained the variability and classification of samples, highlighting chemical markers that discriminate each organ/stage. Leaves were found to be rich in 5‐hydroxy‐8‐methyltocotrienol (8.5 μg/mg f.w.), while flowers were abundant in the polyprenylated benzophenone nemorosone with maximum level detected in the fully mature flower bud (43 μg/mg f.w.). Nemorosone and 5‐hydroxy tocotrienoloic acid were isolated from FL6 for full structural characterisation. This is the first report of the NMR assignments of 5‐hydroxy tocotrienoloic acid, and its maximum level was detected in the mature fruit at 50 μg/mg f.w. Seeds as typical storage organ were rich in sugars and omega‐6 fatty acids.Conclusion: To the best of our knowledge, this is the first report on a comparative 1D‐/2D‐NMR approach to assess compositional differences in ontogeny studies compared with LC‐MS exemplified by Clusia organs. Results derived from this study provide better understanding of the stages at which maximal production of natural compounds occur and elucidate in which developmental stages the enzymes responsible for the production of such metabolites are preferentially expressed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 207
TI  - Diversification of a novel α‐galactosyl ceramide hotspot boosts the adjuvant properties in parenteral and mucosal vaccines
JO  - Angew. Chem. Int. Ed.
PY  - 2024
SP  - e202310983
AU  - Méndez, Y.
AU  - Vasco, A. V.
AU  - Ebensen, T.
AU  - Schulze, K.
AU  - Yousefi, M.
AU  - Davari, M. D.
AU  - Wessjohann, L. A.
AU  - Guzmán, C. A.
AU  - Rivera, D. G.
AU  - Westermann, B.
AU  - 
VL  - 63
UR  - https://doi.org/10.1002/anie.202310983
DO  - 10.1002/anie.202310983
AB  - The development of potent adjuvants is an important step for improving the performance of subunit vaccines. CD1d agonists, such as the prototypical α‐galactosyl ceramide (α‐GalCer), are of special interest due to their ability to activate iNKT cells and trigger rapid dendritic cell maturation and B‐cell activation. Herein, we introduce a novel derivatization hotspot at the α‐GalCer skeleton, namely the N‐substituent at the amide bond. The multicomponent diversification of this previously unexplored glycolipid chemotype space permitted the introduction of a variety of extra functionalities that can either potentiate the adjuvant properties or serve as handles for further conjugation to antigens toward the development of self‐adjuvanting vaccines. This strategy led to the discovery of compounds eliciting enhanced antigen‐specific T cell stimulation and a higher antibody response when delivered by either the parenteral or the mucosal route, as compared to a known potent CD1d agonist. Notably, various functionalized α‐GalCer analogues showed a more potent adjuvant effect after intranasal immunization than a PEGylated α‐GalCer analogue previously optimized for this purpose. Ultimately, this work could open multiple avenues of opportunity for the use of mucosal vaccines against microbial infections.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 206
TI  - Saccharomyces cerevisiae
            biofactory to produce naringenin using a systems biology approach and a bicistronic vector expression strategy in flavonoid production
JO  - Microbiology Spectrum
PY  - 2024
SP  - e03374-23
AU  - Mejía-Manzano, L. A.
AU  - Ortiz-Alcaráz, C. I.
AU  - Parra Daza, L. E.
AU  - Suarez Medina, L.
AU  - Vargas-Cortez, T.
AU  - Fernández-Niño, M.
AU  - González Barrios, A. F.
AU  - González-Valdez, J.
AU  - 
VL  - 12
UR  - https://doi.org/10.1128/spectrum.03374-23
DO  - 10.1128/spectrum.03374-23
AB  - Naringenin is the central flavonoid in the biosynthesis of several bioactive compounds and presents a growing demand for its nutraceutical properties. Naringenin extraction from plants is non-viable due to low yields, and microbial platforms could represent a controlled and sustained alternative to produce it using several metabolic engineering tools. This study shows the naringenin production in
            Saccharomyces cerevisiae
            from glucose through a combined approach of systems biology, enzyme criteria selection, and a molecular engineering strategy.
            In silico
            prediction using a mixed integer linear programming (MILP) algorithm showed that the phenylpropanoid pathway was the shortest and most viable metabolic pathway. Two biscistronic constructs were generated using the PTV-1 2A peptide sequence, and a naringenin biofactory was assembled with the phenylalanine ammonia-lyase/tyrosine ammonia-lyase genes encoding phenylalanine/tyrosine ammonia-lyase (Rhodobacter capsulatus), 4-coumaroyl (4 Cl) encoding a
            p-coumaroyl-CoA ligase (Solanum lycopersicum), CHS encoding chalcone synthase (Hypericum androsaemum), and CHI encoding a chalcone isomerase (Glycine max). Naringenin productivity in batch fermentation was about 40.67 ± 3.47 µg/Lh with a 6.10 ± 0.52 mg/L titer (22.41 ± 1.91 µM) and a 3.26 ± 1.36 mg/g yield (YP/S) with the detection of additional flavonoids. The obtained concentration is better than other related works in diverse engineered microorganisms. The results suggest a successful and optimizable alternative for the heterologous flavanone production in yeast combined with bicistronic expression mediated by a 2A peptide sequence for the first time. This strategy supports the production of extensive routes for other nutraceutical compounds.
          
          
            IMPORTANCE
            
              Flavonoids are a group of compounds generally produced by plants with proven biological activity, which have recently beeen recommended for the treatment and prevention of diseases and ailments with diverse causes. In this study, naringenin was produced in adequate amounts in yeast after
              in silico
              design. The four genes of the involved enzymes from several organisms (bacteria and plants) were multi-expressed in two vectors carrying each two genes linked by a short viral peptide sequence. The batch kinetic behavior of the product, substrate, and biomass was described at lab scale. The engineered strain might be used in a more affordable and viable bioprocess for industrial naringenin procurement.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 202
TI  - Pod Production Dynamics and Pod Size Distribution of Theobroma cacao L. Clone CCN 51 in Full Sunlight
JO  - International Journal of Agronomy
PY  - 2024
SP  - 1-9
AU  - Jaimez, R. E.
AU  - Barragan, L.
AU  - Fernández-Niño, M.
AU  - Larreal B, O. J.
AU  - Flores, B.
AU  - 
VL  - 2024
UR  - https://doi.org/10.1155/2024/4242270
DO  - 10.1155/2024/4242270
AB  - Cacao fruit production dynamics vary from one location to another and are conditioned by the number of pods produced per tree. During cocoa pod development, the strength of the carbon sink varies depending on the demand exerted by the pods, which is proportional to the size. The relationship between cocoa pod production dynamics and size distribution is still poorly understood. Dissecting this relationship is an important step toward further improving cocoa crop management. In this study, the annual yield dynamics and quantity of cocoa pods produced by popular, highly productive, and widespread clone CCN 51 were investigated, based on six size classes observed during its fructification. Growth parameters were determined as weekly increments of pod length and diameter, whereas daily increments were estimated using the logistic Richards model. The fruiting cycle was characterized by the coexistence of fruits of various sizes where the number of pods belonging to each size class changes throughout the fruiting season. Fruit production varied following a seasonal pattern, reaching a maximum of 36 pods/tree, in trees cultivated in full sunlight, of which approximately 55% matured and were harvested. The peak carbon sink demand occurs when the tree pods have the highest numbers of pods. During this period, 65% of the pods had lengths between 5 and 15 cm, which corresponds to the period of the highest pod growth rate. The average length values of the harvested pods were generally below 23 cm and rarely exceeded 7 pods/tree. The Richard model proved to describe accurately the pod growth rates for CCN 51. This represents a promising tool to determine pod growth in other cultivars of relevance for the cocoa industry, which is essential to improve cocoa crop management.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 201
TI  - How can we unlock the full potential of marine biological resources for novel drug discovery in an effective and ethical way?
JO  - Expert Opinion on Drug Discovery
PY  - 2024
SP  - 125-130
AU  - Hussain, H.
AU  - 
VL  - 19
UR  - https://doi.org/10.1080/17460441.2023.2285402
DO  - 10.1080/17460441.2023.2285402
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 200
TI  - Bioactive and flavor compounds in cocoa liquor and their traceability over the major steps of cocoa post-harvesting processes
JO  - Food Chem.
PY  - 2024
SP  - 137529
AU  - Herrera-Rocha, F.
AU  - León-Inga, A. M.
AU  - Aguirre Mejía, J. L.
AU  - Rodríguez-López, C. M.
AU  - Chica, M. J.
AU  - Wessjohann, L. A.
AU  - González Barrios, A. F.
AU  - Cala, M. P.
AU  - Fernández-Niño, M.
AU  - 
VL  - 435
UR  - https://doi.org/10.1016/j.foodchem.2023.137529
DO  - 10.1016/j.foodchem.2023.137529
AB  - The production of fine-flavor cocoa represents a promising avenue to enhance socioeconomic development in Colombia and Latin America. Premium chocolate is obtained through a post-harvesting process, which relies on semi-standardized techniques. The change in the metabolic profile during cocoa processing considerably impacts flavor and nutraceutical properties of the final product. Understanding this impact considering both volatiles and non-volatile compounds is crucial for process and product re-engineering of cocoa post-harvesting. Consequently, this work studied the metabolic composition of cocoa liquor by untargeted metabolomics and lipidomics. This approach offered a comprehensive view of cocoa biochemistry, considering compounds associated with bioactivity and flavor in cocoa liquor. Their variations were traced back over the cocoa processing (i.e., drying, and roasting), highlighting their impact on flavor development and the nutraceutical properties. These results represent the basis for future studies aimed to re-engineer cocoa post-harvesting considering the variation of key flavor and bioactive compounds over processing.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 199
TI  - Characterization of the active site in the thiocyanate-forming protein from Thlaspi arvense (TaTFP) using EPR spectroscopy
JO  - Biol. Chem.
PY  - 2024
SP  - 105-118
AU  - Hashemi Haeri, H.
AU  - Schneegans, N.
AU  - Eisenschmidt-Bönn, D.
AU  - Brandt, W.
AU  - Wittstock, U.
AU  - Hinderberger, D.
AU  - 
VL  - 405
UR  - https://doi.org/10.1515/hsz-2023-0187
DO  - 10.1515/hsz-2023-0187
AB  - Glucosinolates are plant thioglucosides, which act as chemical defenses. Upon tissue damage, their myrosinase-catalyzed hydrolysis yields aglucones that rearrange to toxic isothiocyanates. Specifier proteins such as thiocyanate-forming protein from Thlaspi arvense (TaTFP) are non-heme iron proteins, which capture the aglucone to form alternative products, e.g. nitriles or thiocyanates. To resolve the electronic state of the bound iron cofactor in TaTFP, we applied continuous wave electron paramagnetic resonance (CW EPR) spectroscopy at X-and Q-band frequencies (∼9.4 and ∼34 GHz). We found characteristic features of high spin and low spin states of a d5 electronic configuration and local rhombic symmetry during catalysis. We monitored the oxidation states of bound iron during conversion of allylglucosinolate by myrosinase and TaTFP in presence and absence of supplemented Fe2+. Without added Fe2+, most high spin features of bound Fe3+ were preserved, while different g’-values of the low spin part indicated slight rearrangements in the coordination sphere and/or structural geometry. We also examined involvement of the redox pair Fe3+/Fe2 in samples with supplemented Fe2+. The absence of any EPR signal related to Fe3+ or Fe2+ using an iron-binding deficient TaTFP variant allowed us to conclude that recorded EPR signals originated from the bound iron cofactor.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 198
TI  - Combinatorial biosynthesis in yeast leads to over 200 diterpenoids
JO  - Metab. Eng.
PY  - 2024
SP  - 193-200
AU  - Frey, M.
AU  - Bathe, U.
AU  - Meink, L.
AU  - Balcke, G. U.
AU  - Schmidt, J.
AU  - Frolov, A.
AU  - Soboleva, A.
AU  - Hassanin, A.
AU  - Davari, M. D.
AU  - Frank, O.
AU  - Schlagbauer, V.
AU  - Dawid, C.
AU  - Tissier, A.
AU  - 
VL  - 82
UR  - https://doi.org/10.1016/j.ymben.2024.02.006
DO  - 10.1016/j.ymben.2024.02.006
AB  - Diterpenoids form a diverse group of natural products, many of which are or could become pharmaceuticals or industrial chemicals. The modular character of diterpene biosynthesis and the promiscuity of the enzymes involved make combinatorial biosynthesis a promising approach to generate libraries of diverse diterpenoids. Here, we report on the combinatorial assembly in yeast of ten diterpene synthases producing (+)-copalyldiphosphate-derived backbones and four cytochrome P450 oxygenases (CYPs) in diverse combinations. This resulted in the production of over 200 diterpenoids. Based on literature and chemical database searches, 162 of these compounds can be considered new-to-Nature. The CYPs accepted most substrates they were given but remained regioselective with few exceptions. Our results provide the basis for the systematic exploration of the diterpenoid chemical space in yeast using sequence databases.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 197
TI  - Characterization of the structure, anti-inflammatory activity and molecular docking of a neutral polysaccharide separated from American ginseng berries
JO  - Biomedicine &amp; Pharmacotherapy
PY  - 2024
SP  - 116521
AU  - Feng, Q.
AU  - Yan, H.
AU  - Feng, Y.
AU  - Cui, L.
AU  - Hussain, H.
AU  - Park, J. H.
AU  - Kwon, S. W.
AU  - Xie, L.
AU  - Zhao, Y.
AU  - Zhang, Z.
AU  - Li, J.
AU  - Wang, D.
AU  - 
VL  - 174
UR  - https://doi.org/10.1016/j.biopha.2024.116521
DO  - 10.1016/j.biopha.2024.116521
AB  - Aim: American ginseng berries, grown in the aerial parts and harvested in August, are a potentially valuable material. The aim of the study was to analyze the specific polysaccharides in American ginseng berries, and to demonstrate the anti-inflammation effect through in vitro and in vivo experiments and molecular docking. Methods: After deproteinization and dialysis, the extracted crude polysaccharide was separated and purified. The structure of the specific isolated polysaccharide was investigated by Fourier Transform infrared spectroscopy (FT-IR), GC-MS and nuclear magnetic resonance (NMR), and anti-inflammatory activity was evaluated using in vitro and in vivo models (Raw 264.7 cells and zebrafish). Molecular docking was used to analyze the binding capacity and interaction with cyclooxygenase-2 (COX-2). Results: A novel neutral polysaccharide fraction (AGBP-A) was isolated from American ginseng berries. The structural analysis demonstrated that AGBP-A had a weight-average molecular weight (Mw) of 122,988 Da with a dispersity index (Mw/Mn) value of 1.59 and was composed of arabinose and galactose with a core structure containing →6)-Gal-(1→ residues as the backbone and a branching substitution at the C3 position. The sidechains comprised of α-L-Ara-(1→, α-L-Ara-(1→, →5)-α-L-Ara-(1→, β-D-Gal-(1→. The results showed that it significantly decreased pro-inflammatory cytokines in the cell model. In a zebrafish model, AGBP-A reduced the massive recruitment of neutrophils to the caudal lateral line neuromast, suggesting the relief of inflammation. Molecular docking was used to analyze the combined capacity and interaction with COX-2. Conclusion: Our study indicated the potential efficacy of AGBP-A as a safe and valid natural anti-inflammatory component.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 196
TI  - Antimicrobial action mechanisms of natural compounds isolated from endophytic microorganisms
JO  - Antibiotics
PY  - 2024
SP  - 271
AU  - Eshboev, F.
AU  - Mamadalieva, N.
AU  - Nazarov, P.
AU  - Hussain, H.
AU  - Katanaev, V.
AU  - Egamberdieva, D.
AU  - Azimova, S.
AU  - 
VL  - 13
UR  - https://doi.org/10.3390/antibiotics13030271
DO  - 10.3390/antibiotics13030271
AB  - Infectious diseases are a significant challenge to global healthcare, especially in the face of increasing antibiotic resistance. This urgent issue requires the continuous exploration and development of new antimicrobial drugs. In this regard, the secondary metabolites derived from endophytic microorganisms stand out as promising sources for finding antimicrobials. Endophytic microorganisms, residing within the internal tissues of plants, have demonstrated the capacity to produce diverse bioactive compounds with substantial pharmacological potential. Therefore, numerous new antimicrobial compounds have been isolated from endophytes, particularly from endophytic fungi and actinomycetes. However, only a limited number of these compounds have been subjected to comprehensive studies regarding their mechanisms of action against bacterial cells. Furthermore, the investigation of their effects on antibiotic-resistant bacteria and the identification of biosynthetic gene clusters responsible for synthesizing these secondary metabolites have been conducted for only a subset of these promising compounds. Through a comprehensive analysis of current research findings, this review describes the mechanisms of action of antimicrobial drugs and secondary metabolites isolated from endophytes, antibacterial activities of the natural compounds derived from endophytes against antibiotic-resistant bacteria, and biosynthetic gene clusters of endophytic fungi responsible for the synthesis of bioactive secondary metabolites.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 194
TI  - Sydnone imines as a new class of promising plant growth and stress tolerance modulators—A first experimental structure–activity overview
JO  - Stresses
PY  - 2024
SP  - 133-154
AU  - Cherevatskaya, M.
AU  - Cherepanov, I.
AU  - Kalganova, N.
AU  - Erofeeva, N.
AU  - Romanovskaya, E.
AU  - Frolov, A.
AU  - Bilova, T.
AU  - Moiseev, S.
AU  - Wessjohann, L. A.
AU  - 
VL  - 4
UR  - https://doi.org/10.3390/stresses4010008
DO  - 10.3390/stresses4010008
AB  - Due to the oncoming climate changes, various environmental stresses (drought, salinity, heavy-metals, low or high temperatures, etc.) might dramatically affect crop yields and the quality of produced foods. Therefore, to meet the growing food demand of the human population, improvement of stress tolerance of the currently cultured crops is required. The knowledge of the molecular underlying mechanisms provides a versatile instrument to correct plant metabolism via chemical tools and to thereby increase their adaptive potential. This will preserve crop productivity and quality under abiotic stress conditions. Endogenously produced nitric oxide (NO) is one of the key signaling factors activating stress tolerance mechanisms in plants. Thus, the application of synthetic NO donors as stress-protective phytoeffectors might support maintaining plant growth and productivity under stressful conditions. Sydnone imines (sydnonimines) are a class of clinically established mesoionic heterocyclic NO donors which represent a promising candidate group for such phytoeffectors. Therefore, here, we provide an overview of the current progress in the application of sydnone imines as exogenous NO donors in plants, with a special emphasis on their potential as herbicides as well as herbicide antidotes, growth stimulants and stress protectors triggering plant tolerance mechanisms. We specifically address the structure–activity relationships in the context of the growth modulating activity of sydnone imines. Growth stimulating or antidote effects are typical for 4-α-hydroxybenzyl derivatives of sydnone imines containing an alkyl substituent in position N-3. The nature of the substituent of the N-6 atom has a significant influence on the activity profile and the intensity of the effect. Nevertheless, further investigations are necessary to establish reliable structure–activity relationships (SAR). Consequently, sydnone imines might be considered promising phytoeffector candidates, which are expected to exert either protective effects on plants growing under unfavorable conditions, or herbicidal ones, depending on the exact structure.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 193
TI  - Ultrasonic-assisted extraction of flavonoids from peanut leave and stem using deep eutectic solvents and its molecular mechanism
JO  - Food Chem.
PY  - 2024
SP  - 137497
AU  - Cheng, Y.
AU  - Zhao, H.
AU  - Cui, L.
AU  - Hussain, H.
AU  - Nadolnik, L.
AU  - Zhang, Z.
AU  - Zhao, Y.
AU  - Qin, X.
AU  - Li, J.
AU  - Park, J. H.
AU  - Wang, D.
AU  - 
VL  - 434
UR  - https://doi.org/10.1016/j.foodchem.2023.137497
DO  - 10.1016/j.foodchem.2023.137497
AB  - Natural bioactive compounds extracted from agricultural by-products have received considerable attentions. Twenty-two kinds of deep eutectic solvents (DESs) with ultrasonic were screened to extract flavonoids from peanut leave and stem. ChCl-acetic acid (ChCl-Aa) with 1:2 M ratio resulted in more effective extraction of flavonoids compared to other solvents The best extraction conditions were found to be at a 27% water content in DES/H2O, for 43 min with 31:1 g/mL liquid/solid ratio, giving 2.980 mg/g dw of flavonoids through the response surface method. SEM showed that ChCl-Aa had a certain dissociation impact on the sample matrix, while 1H NMR analysis revealed the formation of hydrogen bonds between daidzein and ChCl-Aa. Changes in the H–bond length and number were observed by the B3LYP/6-31G (d,p) level of theory to confirm the experimental spectra. This study reveals that DESs are efficient for obtaining value-added products and could applied to other natural products.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 192
TI  - Assessment of metabolome diversity in black and white pepper in response to autoclaving using MS- and NMR-based metabolomics and in relation to its remote and direct antimicrobial effects against food-borne pathogens
JO  - RSC Adv.
PY  - 2024
SP  - 10799-10813
AU  - Baky, M. H.
AU  - Kamal, I. M.
AU  - Wessjohann, L. A.
AU  - Farag, M. A.
AU  - 
VL  - 14
UR  - https://doi.org/10.1039/D4RA00100A
DO  - 10.1039/d4ra00100a
AB  - Piper nigrum L. (black and white peppercorn) is one of the most common culinary spices used worldwide. The current study aims to dissect pepper metabolome using 1H-NMR targeting of its major primary and secondary metabolites. Eighteen metabolites were identified with piperine detected in black and white pepper at 20.2 and 23.9 mg mg−1, respectively. Aroma profiling using HS-SPME coupled to GC-MS analysis and in the context of autoclave treatment led to the detection of a total of 52 volatiles with an abundance of b-caryophyllene at 82% and 59% in black and white pepper, respectively. Autoclaving of black and white pepper revealed improvement of pepper aroma as manifested by an increase in oxygenated compounds\' level. In vitro remote antimicrobial activity against food-borne Gram-positive and Gram-negative bacteria revealed the highest activity against P. aeruginosa (VP-MIC 16.4 and 12.9 mg mL−1) and a direct effect against Enterobacter cloacae at ca. 11.6 mg mL−1 for both white and black pepper.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - INPR
ID  - 2497
TI  - A transient expression tool box for anthocyanin biosynthesis in Nicotiana benthamiana
JO  - Plant Biotechnol. J.
PY  - 2023
SP  - 
AU  - Grützner, R.
AU  - König, K.
AU  - Horn, C.
AU  - Engler, C.
AU  - Laub, A.
AU  - Vogt, T.
AU  - Marillonnet, S.
AU  - 
VL  - 
UR  - https://doi.org/10.1111/pbi.14261
DO  - 10.1111/pbi.14261
AB  - Transient expression in Nicotiana benthamiana offers a robust platform for the rapid production of complex secondary metabolites. It has proven highly effective in helping identify genes associated with pathways responsible for synthesizing various valuable natural compounds. While this approach has seen considerable success, it has yet to be applied to uncovering genes involved in anthocyanin biosynthetic pathways. This is because only a single anthocyanin, delphinidin 3‐O‐rutinoside, can be produced in N. benthamiana by activation of anthocyanin biosynthesis using transcription factors. The production of other anthocyanins would necessitate the suppression of certain endogenous flavonoid biosynthesis genes while transiently expressing others. In this work, we present a series of tools for the reconstitution of anthocyanin biosynthetic pathways in N. benthamiana leaves. These tools include constructs for the expression or silencing of anthocyanin biosynthetic genes and a mutant N. benthamiana line generated using CRISPR. By infiltration of defined sets of constructs, the basic anthocyanins pelargonidin 3‐O‐glucoside, cyanidin 3‐O‐glucoside and delphinidin 3‐O‐glucoside could be obtained in high amounts in a few days. Additionally, co‐infiltration of supplementary pathway genes enabled the synthesis of more complex anthocyanins. These tools should be useful to identify genes involved in the biosynthesis of complex anthocyanins. They also make it possible to produce novel anthocyanins not found in nature. As an example, we reconstituted the pathway for biosynthesis of Arabidopsis anthocyanin A5, a cyanidin derivative and achieved the biosynthesis of the pelargonidin and delphinidin variants of A5, pelargonidin A5 and delphinidin A5.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - INPR
ID  - 2496
TI  - Maximizing the value of indole-3-carbinol, from its distribution in dietary sources, health effects, metabolism, extraction, and analysis in food and biofluids
JO  - Crit. Rev. Food Sci. Nutr.
PY  - 2023
SP  - 1-22
AU  - Nagia, M.
AU  - Morgan, I.
AU  - Gamel, M. A.
AU  - Farag, M. A.
AU  - 
VL  - 
UR  - https://doi.org/10.1080/10408398.2023.2197065
DO  - 10.1080/10408398.2023.2197065
AB  - Indole-3-carbinol (I3C) is a major dietary component produced in Brassica vegetables from glucosinolates (GLS) upon herbivores’ attack. The compound is gaining increasing interest due to its anticancer activity. However, reports about improving its level in plants or other sources are still rare. Unfortunately, I3C is unstable in acidic media and tends to polymerize rendering its extraction and detection challenging. This review presents a multifaceted overview of I3C regarding its natural occurrence, biosynthesis, isolation, and extraction procedure from dietary sources, and optimization for the best recovery yield. Further, an overview is presented on its metabolism and biotransformation inside the body to account for its health benefits and factors to ensure the best metabolic yield. Compile of the different analytical approaches for I3C analysis in dietary sources is presented for the first time, together with approaches for its detection and its metabolism in body fluids for proof of efficacy. Lastly, the chemopreventive effects of I3C and the underlying action mechanisms are summarized. Optimizing the yield and methods for the detection of I3C will assist for its incorporation as a nutraceutical or adjuvant in cancer treatment programs. Highlighting the complete biosynthetic pathway and factors involved in I3C production will aid for its future biotechnological production.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 292
TI  - Modulating substrate specificity of Rhizobium sp. Histamine Dehydrogenase through protein engineering for food quality applications
JO  - Molecules
PY  - 2023
SP  - 3748
AU  - Rodríguez-Núñez, K.
AU  - Cortés-Monroy, A.
AU  - Serey, M.
AU  - Ensari, Y.
AU  - Davari, M. D.
AU  - Bernal, C.
AU  - Martinez, R.
AU  - 
VL  - 28
UR  - https://doi.org/10.3390/molecules28093748
DO  - 10.3390/molecules28093748
AB  - Histamine is a biogenic amine found in fish-derived and fermented food products with physiological relevance since its concentration is proportional to food spoilage and health risk for sensitive consumers. There are various analytical methods for histamine quantification from food samples; however, a simple and quick enzymatic detection and quantification method is highly desirable. Histamine dehydrogenase (HDH) is a candidate for enzymatic histamine detection; however, other biogenic amines can change its activity or produce false positive results with an observed substrate inhibition at higher concentrations. In this work, we studied the effect of site saturation mutagenesis in Rhizobium sp. Histamine Dehydrogenase (Rsp HDH) in nine amino acid positions selected through structural alignment analysis, substrate docking, and proximity to the proposed histamine-binding site. The resulting libraries were screened for histamine and agmatine activity. Variants from two libraries (positions 72 and 110) showed improved histamine/agmatine activity ratio, decreased substrate inhibition, and maintained thermal resistance. In addition, activity characterization of the identified Phe72Thr and Asn110Val HDH variants showed a clear substrate inhibition curve for histamine and modified kinetic parameters. The observed maximum velocity (Vmax) increased for variant Phe72Thr at the cost of an increased value for the Michaelis–Menten constant (Km) for histamine. The increased Km value, decreased substrate inhibition, and biogenic amine interference observed for variant Phe72Thr support a tradeoff between substrate affinity and substrate inhibition in the catalytic mechanism of HDHs. Considering this tradeoff for future enzyme engineering of HDH could lead to breakthroughs in performance increases and understanding of this enzyme class.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 291
TI  - Identification and characterization of three new antimicrobial peptides from the marine mollusk Nerita versicolor (Gmelin, 1791)
JO  - Int. J. Mol. Sci.
PY  - 2023
SP  - 3852
AU  - Rodriguez, A.
AU  - Martell-Huguet, E. M.
AU  - González-García, M.
AU  - Alpízar-Pedraza, D.
AU  - Alba, A.
AU  - Vazquez, A. A.
AU  - Grieshober, M.
AU  - Spellerberg, B.
AU  - Stenger, S.
AU  - Münch, J.
AU  - Kissmann, A.-K.
AU  - Rosenau, F.
AU  - Wessjohann, L. A.
AU  - Wiese, S.
AU  - Ständker, L.
AU  - Otero-González, A. J.
AU  - 
VL  - 24
UR  - https://doi.org/10.3390/ijms24043852
DO  - 10.3390/ijms24043852
AB  - Mollusks have been widely investigated for antimicrobial peptides because their humoral defense against pathogens is mainly based on these small biomolecules. In this report, we describe the identification of three novel antimicrobial peptides from the marine mollusk Nerita versicolor. A pool of N. versicolor peptides was analyzed with nanoLC-ESI-MS-MS technology, and three potential antimicrobial peptides (Nv-p1, Nv-p2 and Nv-p3) were identified with bioinformatical predictions and selected for chemical synthesis and evaluation of their biological activity. Database searches showed that two of them show partial identity to histone H4 peptide fragments from other invertebrate species. Structural predictions revealed that they all adopt a random coil structure even when placed near a lipid bilayer patch. Nv-p1, Nv-p2 and Nv-p3 exhibited activity against Pseudomonas aeruginosa. The most active peptide was Nv-p3 with an inhibitory activity starting at 1.5 µg/mL in the radial diffusion assays. The peptides were ineffective against Klebsiella pneumoniae, Listeria monocytogenes and Mycobacterium tuberculosis. On the other hand, these peptides demonstrated effective antibiofilm action against Candida albicans, Candida parapsilosis and Candida auris but not against the planktonic cells. None of the peptides had significant toxicity on primary human macrophages and fetal lung fibroblasts at effective antimicrobial concentrations. Our results indicate that N. versicolor-derived peptides represent new AMP sequences and have the potential to be optimized and developed into antibiotic alternatives against bacterial and fungal infections.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 289
TI  - Agrobacterium-mediated genetic transformation of Withania coagulans (Dunal) with rol A genes and its antioxidant potential
JO  - ACS Omega
PY  - 2023
SP  - 41918-41929
AU  - Rehman, S.
AU  - Hussain, A.
AU  - Ullah, M.
AU  - Ali, E.
AU  - Mojzych, M.
AU  - Naqvi, S. A. R.
AU  - Ali, A.
AU  - Ali, M.
AU  - Gomaa, E.
AU  - Ghoneim, S. S. M.
AU  - Mirza, B.
AU  - Ring, K. K.
AU  - Hussain, H.
AU  - Rauf, A.
AU  - Rehman, N. U.
AU  - Attique, F.
AU  - 
VL  - 8
UR  - https://doi.org/10.1021/acsomega.3c07069
DO  - 10.1021/acsomega.3c07069
AB  - In ancient times, Withania coagulans Dunal was used as a herapeutic plant for the treatment of several diseases. This report aims to examine the effect of Agrobacterium tumefactions-mediated transformation of W. coagulans with the rolA gene to enhance secondary metabolite production, antioxidant activity, and anticancer activity of transformed tissues. Before transgenic plant production, the authors designed an efficient methodology for in vitro transformation. In this study, leaf explants were cultured on Murashage and Skoog (MS) media containing different amounts of naphthalene acetic acid (NAA) and benzyl adenine (BA). The best performance for inducing embryogenic callus was in MS medium containing 4 μM NAA and 6.0 μM BA, while the best results for shooting (100%) were obtained at 8 μM benzyl adenine. On the other hand, direct shooting was attained by subculturing leaves on MS medium supplemented with 8 μM benzyl adenine. Prolonged shoots showed excellent in vitro rooting results (80%) with 12 μM indole-3-butyric acid (IBA). The samples were precultivated for 3 days and were followed by 48 h infection with A. tumefaciens strain GV3101 having pCV002. Then, a vector expressed the rol A gene of strain Agrobacterium rhizogenes. Furthermore, three independent transgenic shoot lines and one callus line (T2) were produced and exhibited stable integration of transgene rol A genes, as revealed by PCR analysis. Transgenic strains showed a significant increase in antioxidant potential as compared to untransformed plants. Additionally, LC-MS analysis showed that the transformed strains have a higher withanolide content as compared to untransformed ones. Moreover, the reduced proliferation of prostate cancer cells was observed after treatment with extracts of transgenic plants. Furthermore, these transformed plants exhibited superior antioxidant capability and higher withanolide content than untransformed ones. In conclusion, the reported data can be used to select withanolide-rich germplasm from transformed cell cultures.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 288
TI  - Simple and robust multiple shoot regeneration and root induction cycle from different explants of Hypericum perforatum L. genotypes
JO  - Plant Cell Tiss. Organ Cult.
PY  - 2023
SP  - 1-15
AU  - Ravindran, B. M.
AU  - Rizzo, P.
AU  - Franke, K.
AU  - Fuchs, J.
AU  - D’Auria, J.
AU  - 
VL  - 152
UR  - https://doi.org/10.1007/s11240-022-02370-w
DO  - 10.1007/s11240-022-02370-w
AB  - Hypericum perforatum L. commonly known as Saint John’s Wort (SJW) is an economically important medicinal plant known for accumulating its valuable bioactive compounds in a compartmentalized fashion. The dark glands are very rich in hypericin, and translucent glands are filled with hyperforin. The antibiotic properties of the afore mentioned bioactive compounds make it hard to establish tissue regeneration protocols essential to put in place a transformation platform that is required for testing gene function in this challenging species. In this study, we report the establishment of a regeneration and root induction cycle from different types of explants. The regeneration cycle was set up for the continuous supply of roots and leaf explants for downstream transformation experiments. The most effective medium to obtain multiple shoot-buds from node cultures was MS (Murashige and Skoog, Physiol Plant 15:473–497, 1962) medium supplemented with 0.5 mg L−1 6-Benzylaminopurine (BAP) and 0.5 mg L−1 indole-3-butyric acid (IBA). The same combination yielded copious amounts of shoots from root and leaf explants as well. For rooting the elongated shoots, MS medium devoid of plant growth regulators (PGRs) was sufficient. Nevertheless, addition of a low amount of IBA improved the quantity and quality of roots induced. Additionally, the roots obtained on a medium containing IBA readily developed shoot buds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 287
TI  - Correction to: Simple and robust multiple shoot regeneration and root induction cycle from different explants of Hypericum perforatum L. genotypes
JO  - Plant Cell Tiss. Organ Cult.
PY  - 2023
SP  - 19
AU  - Ravindran, B. M.
AU  - Rizzo, P.
AU  - Franke, K.
AU  - Fuchs, J.
AU  - D’Auria, J.
AU  - 
VL  - 152
UR  - https://doi.org/10.1007/s11240-022-02418-x
DO  - 10.1007/s11240-022-02418-x
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 286
TI  - Correction to: Simple and robust multiple shoot regeneration and root induction cycle from different explants of Hypericum perforatum L. genotypes
JO  - Plant Cell Tiss. Organ Cult.
PY  - 2023
SP  - 17
AU  - Ravindran, B. M.
AU  - Rizzo, P.
AU  - Franke, K.
AU  - Fuchs, J.
AU  - D’Auria, J.
AU  - 
VL  - 152
UR  - https://doi.org/10.1007/s11240-022-02382-6
DO  - 10.1007/s11240-022-02382-6
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 285
TI  - Molecular modes of action of an aqueous Nerium oleander extract in cancer cells in vitro and in vivo
JO  - Molecules
PY  - 2023
SP  - 1871
AU  - Rashan, L. J.
AU  - Özenver, N.
AU  - Boulos, J. C.
AU  - Dawood, M.
AU  - Roos, W. P.
AU  - Franke, K.
AU  - Papasotiriou, I.
AU  - Wessjohann, L. A.
AU  - Fiebig, H.-H.
AU  - Efferth, T.
AU  - 
VL  - 28
UR  - https://doi.org/10.3390/molecules28041871
DO  - 10.3390/molecules28041871
AB  - Cancer drug resistance remains a major obstacle in clinical oncology. As most anticancer drugs are of natural origin, we investigated the anticancer potential of a standardized cold-water leaf extract from Nerium oleander L., termed Breastin. The phytochemical characterization by nuclear magnetic resonance spectroscopy (NMR) and low- and high-resolution mass spectrometry revealed several monoglycosidic cardenolides as major constituents (adynerin, neritaloside, odoroside A, odoroside H, oleandrin, and vanderoside). Breastin inhibited the growth of 14 cell lines from hematopoietic tumors and 5 of 6 carcinomas. Remarkably, the cellular responsiveness of odoroside H and neritaloside was not correlated with all other classical drug resistance mechanisms, i.e., ATP-binding cassette transporters (ABCB1, ABCB5, ABCC1, ABCG2), oncogenes (EGFR, RAS), tumor suppressors (TP53, WT1), and others (GSTP1, HSP90, proliferation rate), in 59 tumor cell lines of the National Cancer Institute (NCI, USA), indicating that Breastin may indeed bypass drug resistance. COMPARE analyses with 153 anticancer agents in 74 tumor cell lines of the Oncotest panel revealed frequent correlations of Breastin with mitosis-inhibiting drugs. Using tubulin-GFP-transfected U2OS cells and confocal microscopy, it was found that the microtubule-disturbing effect of Breastin was comparable to that of the tubulin-depolymerizing drug paclitaxel. This result was verified by a tubulin polymerization assay in vitro and molecular docking in silico. Proteome profiling of 3171 proteins in the NCI panel revealed protein subsets whose expression significantly correlated with cellular responsiveness to odoroside H and neritaloside, indicating that protein expression profiles can be identified to predict the sensitivity or resistance of tumor cells to Breastin constituents. Breastin moderately inhibited breast cancer xenograft tumors in vivo. Remarkably, in contrast to what was observed with paclitaxel monotherapy, the combination of paclitaxel and Breastin prevented tumor relapse, indicating Breastin’s potential for drug combination regimens.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 284
TI  - Hijacking chemical reactions of P450 enzymes for altered chemical reactions and asymmetric synthesis
JO  - Int. J. Mol. Sci.
PY  - 2023
SP  - 214
AU  - Rajakumara, E.
AU  - Saniya, D.
AU  - Bajaj, P.
AU  - Rajeshwari, R.
AU  - Giri, J.
AU  - Davari, M. D.
AU  - 
VL  - 24
UR  - https://doi.org/10.3390/ijms24010214
DO  - 10.3390/ijms24010214
AB  - Cytochrome P450s are heme-containing enzymes capable of the oxidative transformation of a wide range of organic substrates. A protein scaffold that coordinates the heme iron, and the catalytic pocket residues, together, determine the reaction selectivity and regio- and stereo-selectivity of the P450 enzymes. Different substrates also affect the properties of P450s by binding to its catalytic pocket. Modulating the redox potential of the heme by substituting iron-coordinating residues changes the chemical reaction, the type of cofactor requirement, and the stereoselectivity of P450s. Around hundreds of P450s are experimentally characterized, therefore, a mechanistic understanding of the factors affecting their catalysis is increasingly vital in the age of synthetic biology and biotechnology. Engineering P450s can enable them to catalyze a variety of chemical reactions viz. oxygenation, peroxygenation, cyclopropanation, epoxidation, nitration, etc., to synthesize high-value chiral organic molecules with exceptionally high stereo- and regioselectivity and catalytic efficiency. This review will focus on recent studies of the mechanistic understandings of the modulation of heme redox potential in the engineered P450 variants, and the effect of small decoy molecules, dual function small molecules, and substrate mimetics on the type of chemical reaction and the catalytic cycle of the P450 enzymes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 283
TI  - Triphenyltin(IV) carboxylates with exceptionally high cytotoxicity against different breast cancer cell lines
JO  - Biomolecules
PY  - 2023
SP  - 595
AU  - Predarska, I.
AU  - Saoud, M.
AU  - Morgan, I.
AU  - Lönnecke, P.
AU  - Kaluđerović, G. N.
AU  - Hey-Hawkins, E.
AU  - 
VL  - 13
UR  - https://doi.org/10.3390/biom13040595
DO  - 10.3390/biom13040595
AB  - Organotin(IV) carboxylates are a class of compounds explored as alternatives to platinum-containing chemotherapeutics due to propitious in vitro and in vivo results, and distinct mechanisms of action. In this study, triphenyltin(IV) derivatives of non-steroidal anti-inflammatory drugs (indomethacin (HIND) and flurbiprofen (HFBP)) are synthesized and characterized, namely [Ph3Sn(IND)] and [Ph3Sn(FBP)]. The crystal structure of [Ph3Sn(IND)] reveals penta-coordination of the central tin atom with almost perfect trigonal bipyramidal geometry with phenyl groups in the equatorial positions and two axially located oxygen atoms belonging to two distinct carboxylato (IND) ligands leading to formation of a coordination polymer with bridging carboxylato ligands. Employing MTT and CV probes, the antiproliferative effects of both organotin(IV) complexes, indomethacin, and flurbiprofen were evaluated on different breast carcinoma cells (BT-474, MDA-MB-468, MCF-7 and HCC1937). [Ph3Sn(IND)] and [Ph3Sn(FBP)], unlike the inactive ligand precursors, were found extremely active towards all examined cell lines, demonstrating IC50 concentrations in the range of 0.076–0.200 µM. Flow cytometry was employed to examine the mode of action showing that neither apoptotic nor autophagic mechanisms were triggered within the first 48 h of treatment. However, both tin(IV) complexes inhibited cell proliferation potentially related to the dramatic reduction in NO production, resulting from downregulation of nitric oxide synthase (iNOS) enzyme expression.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 281
TI  - A step forward to the optimized HlyA type 1 secretion system through directed evolution
JO  - Applied Microbiology and Biotechnology
PY  - 2023
SP  - 5131-5143
AU  - Pourhassan, Z. N.
AU  - Cui, H.
AU  - Muckhoff, N.
AU  - Davari, M. D.
AU  - Smits, S. H. J.
AU  - Schwaneberg, U.
AU  - Schmitt, L.
AU  - 
VL  - 107
UR  - https://doi.org/10.1007/s00253-023-12653-7
DO  - 10.1007/s00253-023-12653-7
AB  - Secretion of proteins into the extracellular space has great advantages for the production of recombinant proteins. Type 1 secretion systems (T1SS) are attractive candidates to be optimized for biotechnological applications, as they have a relatively simple architecture compared to other classes of secretion systems. A paradigm of T1SS is the hemolysin A type 1 secretion system (HlyA T1SS) from Escherichia coli harboring only three membrane proteins, which makes the plasmid-based expression of the system easy. Although for decades the HlyA T1SS has been successfully applied for secretion of a long list of heterologous proteins from different origins as well as peptides, but its utility at commercial scales is still limited mainly due to low secretion titers of the system. To address this drawback, we engineered the inner membrane complex of the system, consisting of HlyB and HlyD proteins, following KnowVolution strategy. The applied KnowVolution campaign in this study provided a novel HlyB variant containing four substitutions (T36L/F216W/S290C/V421I) with up to 2.5-fold improved secretion for two hydrolases, a lipase and a cutinase.
            
              Key points
              • An improvement in protein secretion via the use of T1SS
              • Reaching almost 400 mg/L of soluble lipase into the supernatant
              • A step forward to making E. coli cells more competitive for applying as a secretion host
            
              Graphical Abstract
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 280
TI  - Endogenously produced jasmonates affect leaf growth and improve osmotic stress tolerance in emmer wheat
JO  - Biomolecules
PY  - 2023
SP  - 1775
AU  - Pigolev, A. V.
AU  - Miroshnichenko, D.
AU  - Dolgov, S. V.
AU  - Alekseeva, V. V.
AU  - Pushin, A. S.
AU  - Degtyaryova, V. I.
AU  - Klementyeva, A.
AU  - Gorbach, D.
AU  - Leonova, T.
AU  - Basnet, A.
AU  - Frolov, A. A.
AU  - Savchenko, T. V.
AU  - 
VL  - 13
UR  - https://doi.org/10.3390/biom13121775
DO  - 10.3390/biom13121775
AB  - In light of recent climate change, with its rising temperatures and precipitation changes, we are facing the need to increase the valuable crop’s tolerance against unfavorable environmental conditions. Emmer wheat is a cereal crop with high nutritional value. We investigated the possibility of improving the stress tolerance of emmer wheat by activating the synthesis of the stress hormone jasmonate by overexpressing two genes of the jasmonate biosynthetic pathway from Arabidopsis thaliana, ALLENE OXIDE SYNTHASE (AtAOS) and OXOPHYTODIENOATE REDUCTASE 3 (AtOPR3). Analyses of jasmonates in intact and mechanically wounded leaves of non-transgenic and transgenic plants showed that the overexpression of each of the two genes resulted in increased wounding-induced levels of jasmonic acid and jasmonate-isoleucine. Against all expectations, the overexpression of AtAOS, encoding a chloroplast-localized enzyme, does not lead to an increased level of the chloroplast-formed 12-oxo-phytodienoic acid (OPDA), suggesting an effective conversion of OPDA to downstream products in wounded emmer wheat leaves. Transgenic plants overexpressing AtAOS or AtOPR3 with increased jasmonate levels show a similar phenotype, manifested by shortening of the first and second leaves and elongation of the fourth leaf, as well as increased tolerance to osmotic stress induced by the presence of the polyethylene glycol (PEG) 6000.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 279
TI  - Lipase‐mediated conversion of protecting group silyl ethers: An unspecific side reaction
JO  - ChemBioChem
PY  - 2023
SP  - e202300384
AU  - Pick, L. M.
AU  - Wenzlaff, J.
AU  - Yousefi, M.
AU  - Davari, M.
AU  - Ansorge-Schumacher, M.
AU  - 
VL  - 24
UR  - https://doi.org/10.1002/cbic.202300384
DO  - 10.1002/cbic.202300384
AB  - Silyl ether protecting groups are important tools in organic synthesis, ensuring selective reactions of hydroxyl functional groups. Enantiospecific formation or cleavage could simultaneously enable the resolution of racemic mixtures and thus significantly increase the efficiency of complex synthetic pathways. Based on reports that lipases, which today are already particularly important tools in chemical synthesis, can catalyze the enantiospecific turnover of trimethylsilanol (TMS)-protected alcohols, the goal of this study was to determine the conditions under which such a catalysis occurs. Through detailed experimental and mechanistic investigation, we demonstrated that although lipases mediate the turnover of TMS-protected alcohols, this occurs independently of the known catalytic triad, as this is unable to stabilize a tetrahedral intermediate. The reaction is essentially non-specific and therefore most likely completely independent of the active site. This rules out lipases as catalysts for the resolution of racemic mixtures alcohols through protection or deprotection with silyl groups.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 276
TI  - Design and assembly of a biofactory for (2S)-naringenin production in Escherichia coli: Effects of oxygen transfer on yield and gene expression
JO  - Biomolecules
PY  - 2023
SP  - 565
AU  - Parra Daza, L. E.
AU  - Suarez Medina, L.
AU  - Tafur Rangel, A. E.
AU  - Fernández-Niño, M.
AU  - Mejía-Manzano, L. A.
AU  - González-Valdez, J.
AU  - Reyes, L. H.
AU  - González Barrios, A. F.
AU  - 
VL  - 13
UR  - https://doi.org/10.3390/biom13030565
DO  - 10.3390/biom13030565
AB  - The molecule (2S)-naringenin is a scaffold molecule with several nutraceutical properties. Currently, (2S)-naringenin is obtained through chemical synthesis and plant isolation. However, these methods have several drawbacks. Thus, heterologous biosynthesis has emerged as a viable alternative to its production. Recently, (2S)-naringenin production studies in Escherichia coli have used different tools to increase its yield up to 588 mg/L. In this study, we designed and assembled a bio-factory for (2S)-naringenin production. Firstly, we used several parametrized algorithms to identify the shortest pathway for producing (2S)-naringenin in E. coli, selecting the genes phenylalanine ammonia lipase (pal), 4-coumarate: CoA ligase (4cl), chalcone synthase (chs), and chalcone isomerase (chi) for the biosynthetic pathway. Then, we evaluated the effect of oxygen transfer on the production of (2S)-naringenin at flask (50 mL) and bench (4 L culture) scales. At the flask scale, the agitation rate varied between 50 rpm and 250 rpm. At the bench scale, the dissolved oxygen was kept constant at 5% DO (dissolved oxygen) and 40% DO, obtaining the highest (2S)-naringenin titer (3.11 ± 0.14 g/L). Using genome-scale modeling, gene expression analysis (RT-qPCR) of oxygen-sensitive genes was obtained.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 272
TI  - Unveiling metabolome heterogeneity and new chemicals in 7 tomato varieties via multiplex approach of UHPLC-MS/MS, GC–MS, and UV–Vis in relation to antioxidant effects as analyzed using molecular networking and chemometrics
JO  - Food Chem.
PY  - 2023
SP  - 135866
AU  - Otify, A. M.
AU  - Ibrahim, R. M.
AU  - Abib, B.
AU  - Laub, A.
AU  - Wessjohann, L. A.
AU  - Jiang, Y.
AU  - Farag, M. A.
AU  - 
VL  - 417
UR  - https://doi.org/10.1016/j.foodchem.2023.135866
DO  - 10.1016/j.foodchem.2023.135866
AB  - Tomatoes show diverse phytochemical attributes that contribute to their nutritive and health values. This study comprehensively dissects primary and secondary metabolite profiles of seven tomato varieties. UHPLC-qTOF-MS assisted molecular networking was used to monitor 206 metabolites, 30 of which were first-time to be reported. Flavonoids, as valuable antioxidants, were enriched in light-colored tomatoes (golden sweet, sun gold, and yellow plum) versus high tomatoside A, an antihyperglycemic saponin, in cherry bomb and red plum varieties. UV–Vis analysis revealed similar results with a strong absorbance corresponding to rich phenolic content in light varieties. GC–MS unveiled monosaccharides as the main contributors to samples’ segregation, found abundant in San Marzano tomato accounting for its sweet flavor. Fruits also demonstrated potential antioxidant activities in correlation to their flavonoids and phospholipids. This work provides a complete map of tomatoes’ metabolome heterogeneity for future breeding programs and a comparative approach utilizing different metabolomic platforms for tomato analysis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 270
TI  - Indonesian marine and its medicinal contribution
JO  - Natural Products and Bioprospecting
PY  - 2023
SP  - 38
AU  - Nugraha, A. S.
AU  - Firli, L. N.
AU  - Rani, D. M.
AU  - Hidayatiningsih, A.
AU  - Lestari, N. D.
AU  - Wongso, H.
AU  - Tarman, K.
AU  - Rahaweman, A. C.
AU  - Manurung, J.
AU  - Ariantari, N. P.
AU  - Papu, A.
AU  - Putra, M. Y.
AU  - Pratama, A. N. W.
AU  - Wessjohann, L. A.
AU  - Keller, P. A.
AU  - 
VL  - 13
UR  - https://doi.org/10.1007/s13659-023-00403-1
DO  - 10.1007/s13659-023-00403-1
AB  - The archipelagic country of Indonesia is populated by the densest marine biodiversity in the world which has created strong global interest and is valued by both Indigenous and European settlements for different purposes. Nearly 1000 chemicals have been extracted and identified. In this review, a systematic data curation was employed to collate bioprospecting related manuscripts providing a comprehensive directory based on publications from 1988 to 2022. Findings with significant pharmacological activities are further discussed through a scoping data collection. This review discusses macroorganisms (Sponges, Ascidian, Gorgonians, Algae, Mangrove) and microorganism (Bacteria and Fungi) and highlights significant discoveries, including a potent microtubule stabilizer laulimalide from Hyattella sp., a prospective doxorubicin complement papuamine alkaloid from Neopetrosia cf exigua, potent antiplasmodial manzamine A from Acanthostrongylophora ingens, the highly potent anti trypanosomal manadoperoxide B from Plakortis cfr. Simplex, mRNA translation disrupter hippuristanol from Briareum sp, and the anti-HIV-1 (+)-8-hydroxymanzamine A isolated from Acanthostrongylophora sp. Further, some potent antibacterial extracts were also found from a limited biomass of bacteria cultures. Although there are currently no examples of commercial drugs from the Indonesian marine environment, this review shows the molecular diversity present and with the known understudied biodiversity, reveals great promise for future studies and outcomes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 269
TI  - Metabolomics characterizes early metabolic changes and markers of tolerant Eucalyptus ssp. clones against drought stress
JO  - Phytochemistry
PY  - 2023
SP  - 113715
AU  - Noleto-Dias, C.
AU  - Picoli, E. A. T.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - Tavares, J. F.
AU  - Farag, M. A.
AU  - 
VL  - 212
UR  - https://doi.org/10.1016/j.phytochem.2023.113715
DO  - 10.1016/j.phytochem.2023.113715
AB  - L’Hér. (Myrtaceae) is one of the economically most important and widely cultivated trees for wood crop purposes worldwide. Climatic changes together with the constant need to expand plantations to areas that do not always provide optimal conditions for plant growth highlight the need to assess the impact of abiotic stresses on eucalypt trees. We aimed to unveil the drought effect on the leaf metabolome of commercial clones with differential phenotypic response to this stress. For this, seedlings of 13 clones were grown at well-watered (WW) and water-deficit (WD) conditions and their leaf extracts were subjected to comparative analysis using ultra-high performance liquid chromatography coupled to mass spectrometry (UPLC-MS) and nuclear magnetic resonance spectroscopy (NMR). UPLC-MS and NMR analyses led to the annotation of over 100 molecular features of classes such as cyclitols, phenolics, flavonoids, formylated phloroglucinol compounds (FPCs) and fatty acids. Multivariate data analysis was employed for specimens\' classifications and markers identification from both platforms. The results obtained in this work allowed us to classify clones differing in drought tolerance. Classification models were validated using an extra subset of samples. Tolerant plants exposed to water deficit accumulated arginine, gallic acid derivatives, caffeic acid and tannins at higher levels. In contrast, stressed drought-sensitive clones were characterised by a significant reduction in glucose, inositol and shikimic acid levels. These changes in contrasting drought response eucalypt pave ways for differential outcomes of tolerant and susceptible phenotypes. Under optimal growth conditions, all clones were rich in FPCs. These results can be used for early screening of tolerant clones and to improve our understanding of the role of these biomarkers in Eucalyptus tolerance to drought stress.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 268
TI  - Separation and purification of quinolyridine alkaloids from seeds of Thermopsis lanceolata R. Br. by conventional and pH‐zone‐refining counter‐current chromatography
JO  - J Sep Sci
PY  - 2023
SP  - 2300053
AU  - Ning, F.
AU  - Zhu, H.
AU  - Yan, H.
AU  - Liu, J.
AU  - Aziz, S.
AU  - Hussain, H.
AU  - Song, X.
AU  - Xie, L.
AU  - Meng, Z.
AU  - Cao, G.
AU  - Wang, D.
AU  - 
VL  - 46
UR  - https://doi.org/10.1002/jssc.202300053
DO  - 10.1002/jssc.202300053
AB  - In this work, the preparative separation of quinolyridine alkaloids from seeds of T. lanceolata by conventional and pH-zone-refining counter-current chromatography. Traditional counter-current chromatography separation was performed by a flow-rate changing strategy with a solvent system of ethyl acetate-n-butanol-water (1:9:10, v/v) and 200 mg sample loading. Meanwhile, the pH-zone-refining mode was adopted for separating 2.0 g crude alkaloid extracts with the chloroform-methanol-water (4:3:3, v/v) solvent system using the stationary and mobile phases of 40 mM hydrochloric acid and 10 mM triethylamine. Finally, six compounds, including N-formylcytisine (two conformers) (1), N-acetycytisine (two conformers) (2), (-)-cytisine (3), 13-β-hydroxylthermopsine (4), N-methylcytisine (5), and thermopsine (6) were successfully obtained in the two counter-current chromatography modes with the purities over 96.5%. Moreover, we adopted nuclear magnetic resonance and mass spectrometry for structural characterization. Based on the obtained findings, the pH-zone-refining mode was the efficient method to separate quinolyridine alkaloids relative to the traditional mode.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 266
TI  - Rational reprogramming of the sesquiterpene synthase BcBOT2 yields new terpenes with presilphiperfolane skeleton
JO  - Catal. Sci. Technol.
PY  - 2023
SP  - 233-244
AU  - Nikolaiczyk, V.
AU  - Irwan, J.
AU  - Nguyen, T.
AU  - Fohrer, J.
AU  - Elbers, P.
AU  - Schrank, P.
AU  - Davari, M. D.
AU  - Kirschning, A.
AU  - 
VL  - 13
UR  - https://doi.org/10.1039/D2CY01617F
DO  - 10.1039/d2cy01617f
AB  - Computer-aided rational design of the substrate binding pocket of sesquiterpene synthases BcBOT2 from Botrytis cinerea yielded FPP cyclization products with presilphiperfolane backbone other than the naturally formed sesquiterpene presilphiperfolan-8β-ol. Particularly, amino acids W118 and F138 were found to strongly control the stability and conformation of key cationic intermediates. The W118Q variant forms only presilphiperfolan-9β-ol, whereas the exchange of amino acids at position 138, such as F138V, has a fundamental effect on the course of the cationic cascade. Here, the 1,3-hydride shift en route to presilphiperfolan-8β-ol is suppressed and substituted by a so far unknown 1,2-hydride shift that leads to presilphiperfol-1-ene and presilphiperfolan-1α-ol along with β-caryophyllene and the so far unknown caryophyllene-8β-ol.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 262
TI  - Introduction of aromatic amino acids in electron transfer pathways yielded improved catalytic performance of cytochrome P450s
JO  - Chin. J. Catal.
PY  - 2023
SP  - 81-90
AU  - Meng, S.
AU  - Li, Z.
AU  - Ji, Y.
AU  - Ruff, A. J.
AU  - Liu, L.
AU  - Davari, M. D.
AU  - Schwaneberg, U.
AU  - 
VL  - 49
UR  - https://doi.org/10.1016/S1872-2067(23)64445-6
DO  - 10.1016/s1872-2067(23)64445-6
AB  - Cytochrome P450s are versatile catalysts for biosynthesis applications. In the P450 catalytic cycle, two electrons are required to reduce the heme iron and activate the subsequent reductions through proposed electron transfer pathways (eTPs), which often represent the rate-limiting step in reactions. Herein, the P450 BM3 from Bacillus megaterium was engineered for improved catalytic performance by redesigning proposed eTPs. By introducing aromatic amino acids on eTPs of P450 BM3, the “best” variant P2H02 (A399Y/Q403F) showed 13.9-fold improved catalytic efficiency (kcat/KM = 913.5 L mol−1 s−1) compared with P450 BM3 WT (kcat/KM = 65.8 L mol−1 s−1). Molecular dynamics simulations and electron hopping pathways analysis revealed that aromatic amino acid substitutions bridging the cofactor flavin mononucleotide and heme iron could increase electron transfer rates and improve catalytic performance. Moreover, the introduction of tyrosines showed positive effects on catalytic efficiency by potentially protecting P450 from oxidative damage. In essence, engineering of eTPs by aromatic amino acid substitutions represents a powerful approach to design catalytically efficient P450s (such as CYP116B3) and could be expanded to other oxidoreductases relying on long-range electron transfer pathways.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 258
TI  - Engineering of substrate tunnel of P450 CYP116B3 though machine learning
JO  - Catalysts
PY  - 2023
SP  - 1228
AU  - Liu, Y.
AU  - Li, Z.
AU  - Cao, C.
AU  - Zhang, X.
AU  - Meng, S.
AU  - Davari, M. D.
AU  - Xu, H.
AU  - Ji, Y.
AU  - Schwaneberg, U.
AU  - Liu, L.
AU  - 
VL  - 13
UR  - https://doi.org/10.3390/catal13081228
DO  - 10.3390/catal13081228
AB  - The combinatorial complexity of the protein sequence space presents a significant challenge for recombination experiments targeting beneficial positions. To overcome these difficulties, a machine learning (ML) approach was employed, which was trained on a limited literature dataset and combined with iterative generation and experimental data implementation. The PyPEF method was utilized to identify existing variants and predict recombinant variants targeting the substrate channel of P450 CYP116B3. Through molecular dynamics simulations, eight multiple-substituted improved variants were successfully validated. Specifically, the RMSF of variant A86T/T91H/M108S/A109M/T111P was decreased from 3.06 Å (wild type) to 1.07 Å. Additionally, the average RMSF of the variant A86T/T91P/M108V/A109M/T111P decreased to 1.41 Å, compared to the wild type’s 1.53 Å. Of particular significance was the prediction that the variant A86T/T91H/M108G/A109M/T111P exhibited an activity approximately 15 times higher than that of the wild type. Furthermore, during the selection of the regression model, PLS and MLP regressions were compared. The effect of data size and data relevance on the two regression approaches has been summarized. The aforementioned conclusions provide evidence for the feasibility of the strategy that combines ML with experimental approaches. This integrated strategy proves effective in exploring potential variations within the protein sequence space. Furthermore, this method facilitates a deeper understanding of the substrate channel in P450 CYP116B3.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 257
TI  - Purpurascenines A–C, azepino-indole alkaloids from Cortinarius purpurascens: Isolation, biosynthesis, and activity studies on the 5-HT2A receptor
JO  - J. Nat. Prod.
PY  - 2023
SP  - 1373-1384
AU  - Lam, Y. T. H.
AU  - Hoppe, J.
AU  - Dang, Q. N.
AU  - Porzel, A.
AU  - Soboleva, A.
AU  - Brandt, W.
AU  - Rennert, R.
AU  - Hussain, H.
AU  - Davari, M. D.
AU  - Wessjohann, L.
AU  - Arnold, N.
AU  - 
VL  - 86
UR  - https://doi.org/10.1021/acs.jnatprod.2c00716
DO  - 10.1021/acs.jnatprod.2c00716
AB  - Three previously undescribed azepino-indole alkaloids, named purpurascenines A−C (1−3), together with the new-to-nature 7-hydroxytryptophan (4) as well as two known compounds, adenosine (5) and riboflavin (6), were isolated from fruiting bodies of Cortinarius purpurascens Fr. (Cortinariaceae). The structures of 1−3 were elucidated based on spectroscopic analyses and ECD calculations. Furthermore, the biosynthesis of purpurascenine A (1) was investigated by in vivo experiments using 13C-labeled sodium pyruvate, alanine, and sodium acetate incubated with fruiting bodies of C. purpurascens. The incorporation of 13C into 1 was analyzed using 1D NMR and HRESIMS methods. With [3-13C]-pyruvate, a dramatic enrichment of 13C was observed, and hence a biosynthetic route via a direct Pictet−Spengler reaction between α-keto acids and 7-hydroxytryptophan (4) is suggested for the biosynthesis of purpurascenines A−C (1−3). Compound 1 exhibits no antiproliferative or cytotoxic effects against human prostate (PC-3), colorectal (HCT-116), and breast (MCF-7) cancer cells. An in silico docking study confirmed the hypothesis that purpurascenine A (1) could bind to the 5-HT2A serotonin receptor’s active site. A new functional 5-HT2A receptor activation assay showed no functional agonistic but some antagonistic effects of 1 against the 5-HT-dependent 5-HT2A activation and likely antagonistic effects on putative constitutive activity of the 5-HT2A receptor.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 256
TI  - Challenging structure elucidation of lumnitzeralactone, an ellagic acid derivative from the Mangrove Lumnitzera racemosa
JO  - Mar. Drugs
PY  - 2023
SP  - 242
AU  - Kappen, J.
AU  - Manurung, J.
AU  - Fuchs, T.
AU  - Vemulapalli, S. P. B.
AU  - Schmitz, L. M.
AU  - Frolov, A.
AU  - Agusta, A.
AU  - Muellner-Riehl, A. N.
AU  - Griesinger, C.
AU  - Franke, K.
AU  - Wessjohann, L. A.
AU  - 
VL  - 21
UR  - https://doi.org/10.3390/md21040242
DO  - 10.3390/md21040242
AB  - The previously undescribed natural product lumnitzeralactone (1), which represents a derivative of ellagic acid, was isolated from the anti-bacterial extract of the Indonesian mangrove species Lumnitzera racemosa Willd. The structure of lumnitzeralactone (1), a proton-deficient and highly challenging condensed aromatic ring system, was unambiguously elucidated by extensive spectroscopic analyses involving high-resolution mass spectrometry (HRMS), 1D 1H and 13C nuclear magnetic resonance spectroscopy (NMR), and 2D NMR (including 1,1-ADEQUATE and 1,n-ADEQUATE). Determination of the structure was supported by computer-assisted structure elucidation (CASE system applying ACD-SE), density functional theory (DFT) calculations, and a two-step chemical synthesis. Possible biosynthetic pathways involving mangrove-associated fungi have been suggested.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 255
TI  - One pot synthesis, biological efficacy of AuNPs and Au-Amoxicillin conjugates functionalized with crude flavonoids extract of Micromeria biflora
JO  - Molecules
PY  - 2023
SP  - 3320
AU  - Jalil, K.
AU  - Ahmad, S.
AU  - Islam, N.
AU  - Ullah, R.
AU  - Jalil, Q.
AU  - Sulaiman, S.
AU  - Sajjad, A.
AU  - Ullah, R.
AU  - Alqahtani, A. S.
AU  - Bari, A.
AU  - Hussain, H.
AU  - Ali, E. A.
AU  - 
VL  - 28
UR  - https://doi.org/10.3390/molecules28083320
DO  - 10.3390/molecules28083320
AB  - Amoxicillin is the most widely used antibiotic in human medicine for treating bacterial infections. However, in the present research, Micromeria biflora’s flavonoids extract mediated gold nanoparticles (AuNPs) were conjugated with amoxicillin (Au-amoxi) to study their efficacy against the inflammation and pain caused by bacterial infections. The formation of AuNPs and Au-amoxi conjugates were confirmed by UV–visible surface plasmon peaks at 535 nm and 545 nm, respectively. The scanning electron microscopy (SEM), zeta potential (ZP), and X-ray diffraction (XRD) studies reveal that the size of AuNPs and Au-amoxi are found to be 42 nm and 45 nm, respectively. Fourier-transform infrared spectroscopy (FT-IR) absorption bands at 3200 cm−1, 1000 cm−1, 1500 cm−1, and 1650 cm−1 reveal the possible involvement of different moieties for the formation of AuNPs and Au-amoxi. The pH studies show that AuNPs and Au-amoxi conjugates are stable at lower pH. The carrageenan-induced paw edema test, writhing test, and hot plate test were used to conduct in vivo anti-inflammatory and antinociceptive studies, respectively. According to in vivo anti-inflammatory activity, Au-amoxi compounds have higher efficiency (70%) after 3 h at a dose of 10 mg/kg body weight as compared to standard diclofenac (60%) at 20 mg/kg, amoxicillin (30%) at 100 mg/kg, and flavonoids extract (35%) at 100 mg/kg. Similarly, for antinociceptive activities, writhing test results show that Au-amoxi conjugates produced the same number of writhes (15) but at a lower dose (10 mg/kg) compared to standard diclofenac (20 mg/kg). The hot plate test results demonstrate that the Au-amoxi has a better latency time of 25 s at 10 mg/kg dose when compared to standard Tramadol of 22 s at 30 mg/ kg, amoxicillin of 14 s at 100 mg/kg, and extract of 14 s at 100 mg/kg after placing the mice on the hot plate for 30, 60, and 90 min with a significance of (p ≤ 0.001). These findings show that the conjugation of AuNPs with amoxicillin to form Au-amoxi can boost its anti-inflammatory and antinociceptive potential caused by bacterial infections.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 253
TI  - Identification of the first sulfobetaine hydrogel‐binding peptides via phage display assay
JO  - Macromolecular Rapid Communications
PY  - 2023
SP  - 2200896
AU  - Ihlenburg, R. B. J.
AU  - Petracek, D.
AU  - Schrank, P.
AU  - Davari, M. D.
AU  - Taubert, A.
AU  - Rothenstein, D.
AU  - 
VL  - 44
UR  - https://doi.org/10.1002/marc.202200896
DO  - 10.1002/marc.202200896
AB  - Using the M13 phage display, a series of 7- and 12-mer peptides which interact with new sulfobetaine hydrogels are identified. Two peptides each from the 7- and 12-mer peptide libraries bind to the new sulfobetaine hydrogels with high affinity compared to the wild-type phage lacking a dedicated hydrogel binding peptide. This is the first report of peptides binding to zwitterionic sulfobetaine hydrogels and the study therefore opens up the pathway toward new phage or peptide/hydrogel hybrids with high application potential.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 252
TI  - Unusually cyclized triterpenoids: occurrence, biosynthesis and chemical synthesis
JO  - Nat. Prod. Rep.
PY  - 2023
SP  - 412-451
AU  - Hussain, H.
AU  - Xiao, J.
AU  - Ali, A.
AU  - Green, I. R.
AU  - Westermann, B.
AU  - 
VL  - 40
UR  - https://doi.org/10.1039/D2NP00033D
DO  - 10.1039/d2np00033d
AB  - Covering: 2009 to 2021Biosynthetically, most of the syntheses of triterpenes follow the cascade cyclization and rearrangement of the acyclic precursors viz., squalene (S) and 2,3-oxidosqualene (OS), which lead to the very well known tetra- and pentacyclic triterpene skeletons. Aside from these, numerous other triterpenoid molecules are also reported from various natural sources and their structures are derived from \"S\" and \"OS\" via some unusual cyclization operations which are different from the usual tetra- and pentacyclic frameworks. Numerous compelling advances have been made and reported in the identification of these unusual cyclized mono-, di-, tri- and tetracyclic triterpenes between 2009 and 2021. Besides a dramatic increase in the newly isolated uncommon cyclized triterpenoids, substantial progress in the (bio)-synthesis of these triterpenes has been published along with significant progress in their biological effects. In this review, 180 new unusual cyclized triterpenoids together with their demonstrated biogenetic pathways, syntheses and biological effects will be categorized and discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 251
TI  - Prof. Dr. M. Iqbal Choudhary-A lifetime career dedicated to remarkable services in “natural products sciences”
JO  - Frontiers in Pharmacology
PY  - 2023
SP  - 1119419
AU  - Hussain, H.
AU  - Siddiqui, H.
AU  - Gerothanassis, I. P.
AU  - 
VL  - 14
UR  - https://doi.org/10.3389/fphar.2023.1119419
DO  - 10.3389/fphar.2023.1119419
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 250
TI  - Nanoformulation of Curcuma longa root extract and evaluation of its dissolution potential
JO  - ACS Omega
PY  - 2023
SP  - 1088-1096
AU  - Hussain, A.
AU  - Attique, F.
AU  - Naqvi, S. A. R.
AU  - Ali, A.
AU  - Ibrahim, M.
AU  - Hussain, H.
AU  - Zafar, F.
AU  - Iqbal, R. S.
AU  - Ayub, M. A.
AU  - Assiri, M. A.
AU  - Imran, M.
AU  - Ullah, S.
AU  - 
VL  - 8
UR  - https://doi.org/10.1021/acsomega.2c06258
DO  - 10.1021/acsomega.2c06258
AB  - Medicinal plants have been widely used for therapeutic purposes for a long time, but they have been found to have some major issues such as low water solubility and bioavailability. In the present study, the nanoformulation of Curcuma longa L. plant extract was prepared to enhance its dissolution potential and biological activities. For the formulation of the nanosuspension, an ethanolic extract of C. longa was prepared through Soxhlet extraction using the nanoformulation technique. The nanosuspensions were formulated using four different stabilizers, namely sodium lauryl sulfate (SLS), hydroxy propyl methyl cellulose (HPMC), poly(vinyl alcohol) (PVA), and polysorbate-80 (P-80). The scanning electron microscopy (SEM), polydispersity index, and ζ potential were used for characterization of the nanoformulation. Among all of these, the surfactant stabilizer SLS was found to be the best. The average particle size of the selected optimized nanosuspension was found to be 308.2 nm with a polydispersity index (PDI) value of 0.330. The ζ potential value of the optimized nanosuspension was recorded at −33.3 mV. The SEM image indicated that the particles were slightly agglomerated, which may have occurred during lyophilization of the nanosuspension. The highest dissolution rate recorded at pH = 7 was 192.32 μg/mL, which indicates pH = 7 as the most appropriate condition for the dissolution of the C. longa nanosuspension. The antioxidant, antimicrobial, and antifungal activities of the optimized nanosuspension were also determined with regard to the coarse plant extract. The study findings suggested that the nanoprecipitation approach helps in enhancing the dissolution potential and biological activities of C. longa root extract.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 249
TI  - Marine life as a source for breast cancer treatment: A comprehensive review
JO  - Biomedicine &amp; Pharmacotherapy
PY  - 2023
SP  - 114165
AU  - Hussain, A.
AU  - Bourguet-Kondracki, M.-L.
AU  - Majeed, M.
AU  - Ibrahim, M.
AU  - Imran, M.
AU  - Yang, X.-W.
AU  - Ahmed, I.
AU  - Altaf, A. A.
AU  - Khalil, A. A.
AU  - Rauf, A.
AU  - Wilairatana, P.
AU  - Hemeg, H. A.
AU  - Ullah, R.
AU  - Green, I. R.
AU  - Ali, I.
AU  - Shah, S. T. A.
AU  - Hussain, H.
AU  - 
VL  - 159
UR  - https://doi.org/10.1016/j.biopha.2022.114165
DO  - 10.1016/j.biopha.2022.114165
AB  - Breast cancer, one of the most significant tumors among all cancer cells, still has deficiencies for effective treatment. Moreover, substitute treatments employing natural products as bioactive metabolites has been seriously considered. The source of bioactive metabolites are not only the most numerous but also represent the richest source. A unique source is from the oceans or marine species which demonstrated intriguing chemical and biological diversity which represents an astonishing reserve for discovering novel anticancer drugs. Notably, marine sponges produce the largest amount of diverse bioactive peptides, alkaloids, terpenoids, polyketides along with many secondary metabolites whose potential is mostly therapeutic. In this review, our main focus is on the marine derived secondary metabolites which demonstrated cytotoxic effects towards numerous breast cancer cells and have been isolated from the marine sources such as marine sponges, cyanobacteria, fungi, algae, tunicates, actinomycetes, ascidians, and other sources of marine organisms.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 248
TI  - Editorial for special issue “Natural products as potential source of antidiabetic compounds”
JO  - Current Issues in Molecular Biology
PY  - 2023
SP  - 2699-2702
AU  - Hussain, H.
AU  - 
VL  - 45
UR  - https://doi.org/10.3390/cimb45040176
DO  - 10.3390/cimb45040176
AB  - Natural products (NPs) are characterized by possessing intriguing scaffold diversity along with structural complexity and have been a comprehensive source of lead compounds for drug discovery [...]
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 247
TI  - Advances on dietary polysaccharides and oligosaccharides: Structure and bioactivity
JO  - Food Chemistry: X
PY  - 2023
SP  - 100638
AU  - Hussain, H.
AU  - You, L.
AU  - 
VL  - 18
UR  - https://doi.org/10.1016/j.fochx.2023.100638
DO  - 10.1016/j.fochx.2023.100638
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 244
TI  - Omics approaches to understand cocoa processing and chocolate flavor development: A review
JO  - Food Res. Int.
PY  - 2023
SP  - 112555
AU  - Herrera-Rocha, F.
AU  - Fernández-Niño, M.
AU  - Cala, M. P.
AU  - Duitama, J.
AU  - Barrios, A. F. G.
AU  - 
VL  - 165
UR  - https://doi.org/10.1016/j.foodres.2023.112555
DO  - 10.1016/j.foodres.2023.112555
AB  - The global market of chocolate has increased worldwide during the last decade and is expected to reach a value of USD 200 billion by 2028. Chocolate is obtained from different varieties of Theobroma cacao L, a plant domesticated more than 4000 years ago in the Amazon rainforest. However, chocolate production is a complex process requiring extensive post-harvesting, mainly involving cocoa bean fermentation, drying, and roasting. These steps have a critical impact on chocolate quality. Standardizing and better understanding cocoa processing is, therefore, a current challenge to boost the global production of high-quality cocoa worldwide. This knowledge can also help cocoa producers improve cocoa processing management and obtain a better chocolate. Several recent studies have been conducted to dissect cocoa processing via omics analysis. A vast amount of data has been produced regarding omics studies of cocoa processing performed worldwide. This review systematically analyzes the current data on cocoa omics using data mining techniques and discusses opportunities and gaps for cocoa processing standardization from this data. First, we observed a recurrent report in metagenomics studies of species of the fungi genus Candida and Pichia as well as bacteria from the genus Lactobacillus, Acetobacter, and Bacillus. Second, our analyzes of the available metabolomics data showed clear differences in the identified metabolites in cocoa and chocolate from different geographical origin, cocoa type, and processing stage. Finally, our analysis of peptidomics data revealed characteristic patterns in the gathered data including higher diversity and lower size distribution of peptides in fine-flavor cocoa. In addition, we discuss the current challenges in cocoa omics research. More research is still required to fill gaps in central matter in chocolate production as starter cultures for cocoa fermentation, flavor evolution of cocoa, and the role of peptides in the development of specific flavor notes. We also offer the most comprehensive collection of multi-omics data in cocoa processing gathered from different research articles.Graphical abstract
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 243
TI  - Cultural characterization and antagonistic activity of Cladobotryum virescens against some phytopathogenic fungi and oomycetes
JO  - Agronomy
PY  - 2023
SP  - 389
AU  - Hernández, G.
AU  - Ramos, B.
AU  - Sultani, H. N.
AU  - Ortiz, Y.
AU  - Spengler, I.
AU  - Castañeda, R. F.
AU  - Rivera, D. G.
AU  - Arnold, N.
AU  - Westermann, B.
AU  - Mirabal, Y.
AU  - 
VL  - 13
UR  - https://doi.org/10.3390/agronomy13020389
DO  - 10.3390/agronomy13020389
AB  - In this study, the characteristic growth of Cladobotryum virescens on nine culture media was analyzed. The growing behavior of this fungus was dependent on the culture medium. In vitro analysis showed that oat agar was better than other media tested with the highest conidia production. The antifungal activity against Fusarium chlamydosporum and Alternaria brassicicola was evaluated by the Dual Culture method. C. virescens displayed high activity against both pathogens acting through antibiosis and mycoparasitism. This effect was increased by a higher competitiveness of the strain for the substrate. Furthermore, the crude ethyl acetate extract of the culture broth was tested in vitro against Botrytis cinerea and Septoria tritici, as well as the hemibiotrophic oomycete Phytophthora infestans using a microtiter plate assay at different concentrations. The extract showed excellent inhibition even below 5 ppm. According to these results, we concluded that C. virescens can be considered as a potential biological control agent in agriculture. To the best of our knowledge, this is the first study to investigate C. virescens as a biocontrol agent for different diseases caused by five relevant pathogens that affect cereals and vegetables.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 242
TI  - Machine learning-assisted engineering of light, oxygen, voltage photoreceptor adduct lifetime
JO  - JACS Au
PY  - 2023
SP  - 3311-3323
AU  - Hemmer, S.
AU  - Siedhoff, N. E.
AU  - Werner, S.
AU  - Ölçücü, G.
AU  - Schwaneberg, U.
AU  - Jaeger, K.-E.
AU  - Davari, M. D.
AU  - Krauss, U.
AU  - 
VL  - 3
UR  - https://pubs.acs.org/10.1021/jacsau.3c00440
DO  - 10.1021/jacsau.3c00440
AB  - Naturally occurring and engineered flavin-binding, blue-light-sensing, light, oxygen, voltage (LOV) photoreceptor domains have been used widely to design fluorescent reporters, optogenetic tools, and photosensitizers for the visualization and control of biological processes. In addition, natural LOV photoreceptors with engineered properties were recently employed for optimizing plant biomass production in the framework of a plant-based bioeconomy. Here, the understanding and fine-tuning of LOV photoreceptor (kinetic) properties is instrumental for application. In response to blue-light illumination, LOV domains undergo a cascade of photophysical and photochemical events that yield a transient covalent FMN-cysteine adduct, allowing for signaling. The rate-limiting step of the LOV photocycle is the darkrecovery process, which involves adduct scission and can take between seconds and days. Rational engineering of LOV domains with fine-tuned dark recovery has been challenging due to the lack of a mechanistic model, the long time scale of the process, which hampers atomistic simulations, and a gigantic protein sequence space covering known mutations (combinatorial challenge). To address these issues, we used machine learning (ML) trained on scarce literature data and iteratively generated and implemented experimental data to design LOV variants with faster and slower dark recovery. Over the three prediction−validation cycles, LOV domain variants were successfully predicted, whose adduct-state lifetimes spanned 7 orders of magnitude, yielding optimized tools for synthetic (opto)biology. In summary, our results demonstrate ML as a viable method to guide the design of proteins even with limited experimental data and when no mechanistic model of the underlying physical principles is available.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 240
TI  - Recruitment of distinct
            UDP‐glycosyltransferase families demonstrates dynamic evolution of chemical defense within
            Eucalyptus
            L\'Hér
JO  - New Phytol.
PY  - 2023
SP  - 999-1013
AU  - Hansen, C. C.
AU  - Sørensen, M.
AU  - Bellucci, M.
AU  - Brandt, W.
AU  - Olsen, C. E.
AU  - Goodger, J. Q. D.
AU  - Woodrow, I. E.
AU  - Lindberg Møller, B.
AU  - Neilson, E. H. J.
AU  - 
VL  - 237
UR  - https://doi.org/10.1111/nph.18581
DO  - 10.1111/nph.18581
AB  - The economic and ecologically important genus Eucalyptus is rich in structurally diverse specialized metabolites. While some specialized metabolite classes are highly prevalent across the genus, the cyanogenic glucoside prunasin is only produced by c. 3% of species. To investigate the evolutionary mechanisms behind prunasin biosynthesis in Eucalyptus, we compared de novo assembled transcriptomes, together with online resources between cyanogenic and acyanogenic species. Identified genes were characterized in vivo and in vitro. Pathway characterization of cyanogenic Eucalyptus camphora and Eucalyptus yarraensis showed for the first time that the final glucosylation step from mandelonitrile to prunasin is catalyzed by a novel UDP-glucosyltransferase UGT87. This step is typically catalyzed by a member of the UGT85 family, including in Eucalyptus cladocalyx. The upstream conversion of phenylalanine to mandelonitrile is catalyzed by three cytochrome P450 (CYP) enzymes from the CYP79, CYP706, and CYP71 families, as previously shown. Analysis of acyanogenic Eucalyptus species revealed the loss of different ortholog prunasin biosynthetic genes. The recruitment of UGTs from different families for prunasin biosynthesis in Eucalyptus demonstrates important pathway heterogeneities and unprecedented dynamic pathway evolution of chemical defense within a single genus. Overall, this study provides relevant insights into the tremendous adaptability of these long-lived trees.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 238
TI  - Bichromonol, a dimeric coumarin with anti-HIV activity from the stem bark of Hypericum roeperianum
JO  - Nat. Prod. Res.
PY  - 2023
SP  - 1947-1953
AU  - Fobofou, S. A. T.
AU  - Franke, K.
AU  - Brandt, W.
AU  - Manzin, A.
AU  - Madeddu, S.
AU  - Serreli, G.
AU  - Sanna, G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 37
UR  - https://doi.org/10.1080/14786419.2022.2110094
DO  - 10.1080/14786419.2022.2110094
AB  - Infectious diseases caused by viruses like HIV and SARS-COV-2 (COVID-19) pose serious public health threats. In search for new antiviral small molecules from chemically underexplored Hypericum species, a previously undescribed atropisomeric C8-C8’ linked dimeric coumarin named bichromonol (1) was isolated from the stem bark of Hypericum roeperianum. The structure was elucidated by MS data and NMR spectroscopy. The absolute configuration at the biaryl axis was determined by comparing the experimental ECD spectrum with those calculated for the respective atropisomers. Bichromonol was tested in cell-based assays for cytotoxicity against MT-4 (CC50 ¼ 54 mM) cells and anti-HIV activity in infected MT-4 cells. It exhibits significant activity at EC50 ¼ 6.6–12.0 mM against HIV-1 wild type and its clinically relevant mutant strains. Especially, against the resistant variants A17 and EFVR, bichromonol is more effective than the commercial drug nevirapine and might thus have potential to serve as a new anti-HIV lead.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 237
TI  - Comparison of Balanites aegyptiaca parts: metabolome providing insights into plant health benefits and valorization purposes as analyzed using multiplex GC-MS, LC-MS, NMR-based metabolomics, and molecular networking
JO  - RSC Adv.
PY  - 2023
SP  - 21471-21493
AU  - Farag, M. A.
AU  - Baky, M. H.
AU  - Morgan, I.
AU  - Khalifa, M. R.
AU  - Rennert, R.
AU  - Mohamed, O. G.
AU  - El-Sayed, M. M.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - Ramadan, N. S.
AU  - 
VL  - 13
UR  - https://doi.org/10.1039/D3RA03141A
DO  - 10.1039/d3ra03141a
AB  - Balanites aegyptiaca (L.) Delile (Zygophyllaceae), also known as the desert date, is an edible fruit-producing tree popular for its nutritional and several health benefits. In this study, multi-targeted comparative metabolic profiling and fingerprinting approaches were conducted for the assessment of the nutrient primary and secondary metabolite heterogeneity in different parts, such as leaves, stems, seeds, unripe, and ripe fruits of B. aegyptiaca using nuclear magnetic resonance (NMR), ultra-performance liquid chromatography (UPLC-MS), and gas chromatography mass-spectrometry (GC-MS) based metabolomics coupled to multivariate analyses and in relation to its cytotoxic activities. NMR-based metabolomic study identified and quantified 15 major primary and secondary metabolites belonging to alkaloids, saponins, flavonoids, sugars, and amino and fatty acids. Principal component analysis (PCA) of the NMR dataset revealed α-glucose, sucrose, and isorhamnetin as markers for fruit and stem and unsaturated fatty acids for predominated seeds. Orthogonal projections to latent structure discriminant analysis (OPLS-DA) revealed trigonelline as a major distinctive metabolite in the immature fruit and isorhamnetin as a major distinct marker in the mature fruit. UPLC-MS/MS analysis using feature-based molecular networks revealed diverse chemical classes viz. steroidal saponins, N-containing metabolites, phenolics, fatty acids, and lipids as the constitutive metabolome in Balanites. Gas chromatography-mass spectroscopy (GC-MS) profiling of primary metabolites led to the detection of 135 peaks belonging to sugars, fatty acids/esters, amino acids, nitrogenous, and organic acids. Monosaccharides were detected at much higher levels in ripe fruit and disaccharides in predominate unripe fruits, whereas B. aegyptiaca vegetative parts (leaves and stem) were rich in amino acids and fatty acids. The antidiabetic compounds, viz, nicotinic acid, and trigonelline, were detected in all parts especially unripe fruit in addition to the sugar alcohol D-pinitol for the first time providing novel evidence for B. aegyptiaca use in diabetes. In vitro cytotoxic activity revealed the potential efficacy of immature fruit and seeds as cytotoxic agents against human prostate cancer (PC3) and human colorectal cancer (HCT-116) cell lines. Collectively, such detailed profiling of parts provides novel evidence for B. aegyptiaca medicinal uses.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 236
TI  - Synthesis, crystallographic structure, theoretical analysis, molecular docking studies, and biological activity evaluation of Binuclear Ru(II)-1-Naphthylhydrazine Complex
JO  - Int. J. Mol. Sci.
PY  - 2023
SP  - 689
AU  - Eichhorn, T.
AU  - Kolbe, F.
AU  - Mišić, S.
AU  - Dimić, D.
AU  - Morgan, I.
AU  - Saoud, M.
AU  - Milenković, D.
AU  - Marković, Z.
AU  - Rüffer, T.
AU  - Dimitrić Marković, J.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 24
UR  - https://doi.org/10.3390/ijms24010689
DO  - 10.3390/ijms24010689
AB  - Ruthenium(II)–arene complexes have gained significant research interest due to their possible application in cancer therapy. In this contribution two new complexes are described, namely [{RuCl(η6-p-cymene)}2(μ-Cl)(μ-1-N,N′-naphthyl)]X (X = Cl, 1; PF6, 2), which were fully characterized by IR, NMR, and elemental microanalysis. Furthermore, the structure of 2 in the solid state was determined by a single crystal X-ray crystallographic study, confirming the composition of the crystals as 2·2MeOH. The Hirshfeld surface analysis was employed for the investigation of interactions that govern the crystal structure of 2·2MeOH. The structural data for 2 out of 2·2MeOH was used for the theoretical analysis of the cationic part [{RuCl(η6-p-cymene)}2(μ-Cl)(μ-1-N,N′-naphthyl)]+ (2a) which is common to both 1 and 2. The density functional theory, at B3LYP/6-31+G(d,p) basis set for H, C, N, and Cl atoms and LanL2DZ for Ru ions, was used for the optimization of the 2a structure. The natural bond orbital and quantum theory of atoms in molecules analyses were employed to quantify the intramolecular interactions. The reproduction of experimental IR and NMR spectra proved the applicability of the chosen level of theory. The binding of 1 to bovine serum albumin was examined by spectrofluorimetry and molecular docking, with complementary results obtained. Compound 1 acted as a radical scavenger towards DPPH• and HO• radicals, along with high activity towards cancer prostate and colon cell lines.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 233
TI  - 12-Oxophytodienoate reductase overexpression compromises tolerance to Botrytis cinerea in hexaploid and tetraploid wheat
JO  - Plants
PY  - 2023
SP  - 2050
AU  - Degtyaryov, E.
AU  - Pigolev, A.
AU  - Miroshnichenko, D.
AU  - Frolov, A.
AU  - Basnet, A. T.
AU  - Gorbach, D.
AU  - Leonova, T.
AU  - Pushin, A. S.
AU  - Alekseeva, V.
AU  - Dolgov, S.
AU  - Savchenko, T.
AU  - 
VL  - 12
UR  - https://doi.org/10.3390/plants12102050
DO  - 10.3390/plants12102050
AB  - 12-Oxophytodienoate reductase is the enzyme involved in the biosynthesis of phytohormone jasmonates, which are considered to be the major regulators of plant tolerance to biotic challenges, especially necrotrophic pathogens. However, we observe compromised tolerance to the necrotrophic fungal pathogen Botrytis cinerea in transgenic hexaploid bread wheat and tetraploid emmer wheat plants overexpressing 12-OXOPHYTODIENOATE REDUCTASE-3 gene from Arabidopsis thaliana, while in Arabidopsis plants themselves, endogenously produced and exogenously applied jasmonates exert a strong protective effect against B. cinerea. Exogenous application of methyl jasmonate on hexaploid and tetraploid wheat leaves suppresses tolerance to B. cinerea and induces the formation of chlorotic damages. Exogenous treatment with methyl jasmonate in concentrations of 100 µM and higher causes leaf yellowing even in the absence of the pathogen, in agreement with findings on the role of jasmonates in the regulation of leaf senescence. Thereby, the present study demonstrates the negative role of the jasmonate system in hexaploid and tetraploid wheat tolerance to B. cinerea and reveals previously unknown jasmonate-mediated responses.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 304
TI  - Structural characterization and anti-inflammatory activity of neutral polysaccharides from American ginseng
JO  - Int. J. Biol. Macromol.
PY  - 2023
SP  - 125586
AU  - Xie, L.
AU  - Yan, H.
AU  - Han, L.
AU  - Cui, L.
AU  - Hussain, H.
AU  - Feng, Q.
AU  - Zhao, Y.
AU  - Zhang, Z.
AU  - Li, J.
AU  - Aziz, S.
AU  - He, J.
AU  - Wang, D.
AU  - 
VL  - 248
UR  - https://doi.org/10.1016/j.ijbiomac.2023.125586
DO  - 10.1016/j.ijbiomac.2023.125586
AB  - American ginseng, a precious classic herbal medicine, is used extensively in China for life prolongation purpose. This study aimed to elucidate the structure and anti-inflammatory activity of a neutral polysaccharide isolated from American ginseng (AGP-A). Nuclear magnetic resonance in conjunction with gas chromatography–mass spectrometry were used to analyze AGP-A\'s structure, whereas Raw264.7 cell and zebrafish models were employed to assess its anti-inflammatory activity. According to the results, AGP-A has a molecular weight of 5561 Da and is primarily consisted of glucose. Additionally, linear α-(1 → 4)-glucans with α-D-Glcp-(1 → 6)-α-Glcp-(1→ residues linked to the backbone at C-6 formed the backbone of AGP-A. Furthermore, AGP-A significantly decreased pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in Raw264.7 cell model. AGP-A in zebrafish model significantly lower the massive recruitment of neutrophils to the neuromast of the caudal lateral line. Inflammation may be relieved by the AGP-A component in American ginseng based on these results. In conclusion, our study shows the structural characterization, remarkable anti-inflammatory properties of AGP-A and its potential curative efficacy as a safe, valid natural anti-inflammatory medicine.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 301
TI  - Advancing multicomponent strategies to macrobicyclic peptides
JO  - ChemBioChem
PY  - 2023
SP  - e202300229
AU  - Vasco, A. V.
AU  - Méndez, Y.
AU  - González, C.
AU  - Pérez, C. S.
AU  - Reguera, L.
AU  - Wessjohann, L. A.
AU  - Rivera, D. G.
AU  - 
VL  - 24
UR  - https://doi.org/10.1002/cbic.202300229
DO  - 10.1002/cbic.202300229
AB  - Macrocyclization of peptides is typically used to fix specific bioactive conformations and improve their pharmacological properties. Recently, macrobicyclic peptides have received special attention owing to their capacity to mimic protein structures or be key components of peptide-drug conjugates. Here, we describe the development of novel synthetic strategies for two distinctive types of peptide macrobicycles. A multicomponent macrocyclo-dimerization approach is introduced for the production of interconnected β-turns, allowing two macrocyclic rings to be formed and dimerized in one pot. Also, an on-resin double stapling strategy is described for the assembly of lactam-bridged macrobicycles with stable tertiary folds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 299
TI  - Characterization of the genetic variability within Ziziphus nummularia genotypes by phenotypic traits and SSR markers with special reference to geographic distribution
JO  - Genes
PY  - 2023
SP  - 155
AU  - Uddin, N.
AU  - Muhammad, N.
AU  - Ali, S. S.
AU  - Ullah, R.
AU  - Bari, A.
AU  - Hussain, H.
AU  - Zhu, D.
AU  - 
VL  - 14
UR  - https://doi.org/10.3390/genes14010155
DO  - 10.3390/genes14010155
AB  - Understanding the impacts and constraints of climate change on Ziziphus nummularia′s geographical distribution is crucial for its future sustainability. In this study, we analyze information obtained from the field investigation, the distribution and response of climatic changes of Ziziphus nummularia by the use of ArcGIS analysis. The genetic diversity of 180 genotypes from three populations was studied by morphological attributes and simple sequence repeat (SSR). The results showed that the significant bioclimatic variable limiting the distribution of Z. nummularia was the mean temperature (bio 10_18.tif and bio19). Under the current climatic change, the suitable growth region of Z. nummularia is Swat (35.22° N, 72.42° E), while the future distribution would be Buner (34.39° N, 72.61° E), respectively. A total of 11 phenotypic traits were noted and had significant phenotypic variation among the traits. A total of 120 alleles were amplified. The alleles per locus ranged from 2 to 6, averaging 4.42, whereas PIC ranged from 0.33 to 0.79. Within a mean value of 0.67 per locus, expected heterozygosity was 0.57, observed heterozygosity was 0.661, and average gene diversity was 0.49. Flow estimates (6.41) indicated frequent gene flow within genotypes. The clustering, STRUCTURE, and PCoA analysis indicated Swat and Buner migration routes and evolution as well. The results indicated the prevalence of genetic variability and relationships among Z. nummularia across geographical boundaries had retained unique alleles. This may facilitate the development of agronomically desirable cultivars. However, climate change has impacted species distributions, requiring strategies to conserve genetic resources in different areas.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 298
TI  - Isolation and purification of high polar glycosides from aerial parts of Gynostemma pentaphyllum (Thunb.) Makino by linear gradient counter‐current chromatography coupled with inner‐recycling mode
JO  - J Sep Sci
PY  - 2023
SP  - 2300238
AU  - Sun, X.
AU  - Xu, L.
AU  - Yan, H.
AU  - Li, P.
AU  - Hussain, H.
AU  - Liu, J.
AU  - Zhang, J.
AU  - Wang, D.
AU  - 
VL  - 46
UR  - https://doi.org/10.1002/jssc.202300238
DO  - 10.1002/jssc.202300238
AB  - Gynostemma pentaphyllum (Thunb.) Makino represents the popular health food and supplemental product with broad pharmacological activities. The highly polar glycosides, including flavonoids and saponins, are major effective active components that contain diverse sugar positions and quantities, which result in diverse chemical polarities, making it challenging to separate and isolate these components. The present work described the rapid and efficient linear gradient counter‐current chromatography to preparatively separate glycosides from aboveground parts of G. pentaphyllum. Besides, the ethyl acetate and n‐butanol binary mobile phases were achieved through adjusting associated proportions. Six glycosides, including quercetin‐3‐O‐neohesperidoside (1), kaempferol‐3‐O‐robinobioside (2), kaempferol‐3‐O‐neohesperidoside (3), gypenoside LVI (4), ginsenoside Rb3 (5), and gypenoside XLVI (6), were isolated at the purities greater than 98%. Moreover, electrospray ionization mass spectrometry and nuclear magnetic resonance tandem mass spectrometry were conducted for structural identification. According to our findings, the established linear gradient counter‐current chromatography was an efficient approach to separate the highly polar glycosides from aboveground parts of G. pentaphyllum. Our proposed strategy can be used to separate active compounds from other complex natural products.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 293
TI  - Averrhoa carambola L. fruit and stem metabolites profiling and immunostimulatory action mechanisms against cyclosporine induced toxic effects in rat model as analyzed using UHPLC/MS-MS-based chemometrics and bioassays
JO  - Food Chem. Toxicol.
PY  - 2023
SP  - 114001
AU  - S. Ramadan, N.
AU  - Fayek, N. M.
AU  - M. El-Sayed, M.
AU  - S. Mohamed, R.
AU  - Wessjohann, L. A.
AU  - Farag, M. A.
AU  - 
VL  - 179
UR  - https://doi.org/10.1016/j.fct.2023.114001
DO  - 10.1016/j.fct.2023.114001
AB  - The Averrhoa carambola L. tree encompasses a myriad of phytochemicals contributing to its nutritional and health benefits. The current study aims at investigating the A. carambola L. the metabolite profile grown in tropical and temperate regions represented by fruit and stem, for the first time using UPLC/MS-based molecular networking and chemometrics. Asides, assessment of the immunostimulatory effect of ripe fruit and stem, was compared in relation to metabolite fingerprints. Eighty metabolites were identified, 8 of which are first-time to be reported including 3 dihydrochalcone-C-glycosides, 4 flavonoids, and one phenolic. Multivariate data analysis revealed dihydrochalcones as origin-discriminating metabolites between temperate and tropical grown fruits. Further, an in vivo immunomodulatory assay in a cyclosporine A-induced rat model revealed a potential immune-enhancing effect as manifested by down-regulation of inflammatory markers (IL-6, INF-γ, IL-1, TLR4, and ESR) concurrent with the up-regulation of CD4 level and the CD4/CD8 ratio. Moreover, both extracts suppressed elevation of liver and kidney functions in serum as well as reduction in oxidative stress with concurrent increased levels of T-protein, albumin, globulin, and A/G ratio. This study pinpoints differences in secondary metabolite profiles amongst A. carambola L. accessions from different origins and organ type and its immunomodulatory action mechanisms.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 230
TI  - Prenylated acylphloroglucinol alcohols and peroxides from Hypericum coris
JO  - Phytochem. Lett.
PY  - 2023
SP  - 11-15
AU  - Corrêa dos Santos, C. H.
AU  - Stark, P.
AU  - Rizzo, P.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - 
VL  - 57
UR  - https://doi.org/10.1016/j.phytol.2023.07.011
DO  - 10.1016/j.phytol.2023.07.011
AB  - Two so far undescribed prenylated acylphloroglucinol derivatives were isolated from Hypericum coris (hypercorisins A-B) together with their two, also yet undescribed, peroxide derivatives (hypercorisins C-D), and seven known compounds (2-geranyloxy-1-(2-methylpropanoyl)-phloroglucinol, sucrose, vanillic acid 4-O-β-D-glucoside, chlorogenic acid, neochlorogenic acid, shikimic acid, quercitrin). The structures were determined by means of 1D and 2D NMR experiments and high-resolution mass spectrometry. Hypercorisins A, B and D induced complete inhibition of the gram-positive bacterium Bacillus subtilis at the highest concentration tested (100 μM) but showed no appreciable antibacterial effect on the gram-negative Aliivibrio fischeri nor cytotoxic activity on PC-3 or HCT-116 cancer cell lines.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 229
TI  - Prenylated isoflavanones with antimicrobial potential from the root bark of Dalbergia melanoxylon
JO  - Metabolites
PY  - 2023
SP  - 678
AU  - Chalo, D. M.
AU  - Franke, K.
AU  - Nchiozem-Ngnitedem, V.-A.
AU  - Kakudidi, E.
AU  - Origa-Oryem, H.
AU  - Namukobe, J.
AU  - Kloss, F.
AU  - Yenesew, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 13
UR  - https://doi.org/10.3390/metabo13060678
DO  - 10.3390/metabo13060678
AB  - Dalbergia melanoxylon Guill. &amp; Perr (Fabaceae) is widely utilized in the traditional medicine of East Africa, showing effects against a variety of ailments including microbial infections. Phytochemical investigation of the root bark led to the isolation of six previously undescribed prenylated isoflavanones together with eight known secondary metabolites comprising isoflavanoids, neoflavones and an alkyl hydroxylcinnamate. Structures were elucidated based on HR-ESI-MS, 1- and 2-D NMR and ECD spectra. The crude extract and the isolated compounds of D. melanoxylon were tested for their antibacterial, antifungal, anthelmintic and cytotoxic properties, applying established model organisms non-pathogenic to humans. The crude extract exhibited significant antibacterial activity against Gram-positive Bacillus subtilis (97% inhibition at 50 μg/mL) and antifungal activity against the phytopathogens Phytophthora infestans, Botrytis cinerea and Septoria tritici (96, 89 and 73% at 125 μg/mL, respectively). Among the pure compounds tested, kenusanone H and (3R)-tomentosanol B exhibited, in a panel of partially human pathogenic bacteria and fungi, promising antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium showing MIC values between 0.8 and 6.2 μg/mL. The observed biological effects support the traditional use of D. melanoxylon and warrant detailed investigations of its prenylated isoflavanones as antibacterial lead compounds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 227
TI  - Genome-scale metabolic reconstruction, non-targeted LC-QTOF-MS based metabolomics data, and evaluation of anticancer activity of Cannabis sativa leaf extracts
JO  - Metabolites
PY  - 2023
SP  - 788
AU  - Camargo, F. D. G.
AU  - Santamaria-Torres, M.
AU  - Cala, M. P.
AU  - Guevara-Suarez, M.
AU  - Restrepo, S.
AU  - Sánchez-Camargo, A.
AU  - Fernández-Niño, M.
AU  - Corujo, M.
AU  - Gallo Molina, A. C.
AU  - Cifuentes, J.
AU  - Serna, J. A.
AU  - Cruz, J. C.
AU  - Muñoz-Camargo, C.
AU  - Barrios, A. F. G.
AU  - 
VL  - 13
UR  - https://doi.org/10.3390/metabo13070788
DO  - 10.3390/metabo13070788
AB  - Over the past decades, Colombia has suffered complex social problems related to illicit crops, including forced displacement, violence, and environmental damage, among other consequences for vulnerable populations. Considerable effort has been made in the regulation of illicit crops, predominantly Cannabis sativa, leading to advances such as the legalization of medical cannabis and its derivatives, the improvement of crops, and leaving an open window to the development of scientific knowledge to explore alternative uses. It is estimated that C. sativa can produce approximately 750 specialized secondary metabolites. Some of the most relevant due to their anticancer properties, besides cannabinoids, are monoterpenes, sesquiterpenoids, triterpenoids, essential oils, flavonoids, and phenolic compounds. However, despite the increase in scientific research on the subject, it is necessary to study the primary and secondary metabolism of the plant and to identify key pathways that explore its great metabolic potential. For this purpose, a genome-scale metabolic reconstruction of C. sativa is described and contextualized using LC-QTOF-MS metabolic data obtained from the leaf extract from plants grown in the region of Pesca-Boyaca, Colombia under greenhouse conditions at the Clever Leaves facility. A compartmentalized model with 2101 reactions and 1314 metabolites highlights pathways associated with fatty acid biosynthesis, steroids, and amino acids, along with the metabolism of purine, pyrimidine, glucose, starch, and sucrose. Key metabolites were identified through metabolomic data, such as neurine, cannabisativine, cannflavin A, palmitoleic acid, cannabinoids, geranylhydroquinone, and steroids. They were analyzed and integrated into the reconstruction, and their potential applications are discussed. Cytotoxicity assays revealed high anticancer activity against gastric adenocarcinoma (AGS), melanoma cells (A375), and lung carcinoma cells (A549), combined with negligible impact against healthy human skin cells.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 223
TI  - Characterization and bioactive potential of secondary metabolites isolated from Piper sarmentosum Roxb.
JO  - Int. J. Mol. Sci.
PY  - 2023
SP  - 1328
AU  - Bin Ware, I.
AU  - Franke, K.
AU  - Dube, M.
AU  - Ali El Enshasy, H.
AU  - Wessjohann, L. A.
AU  - 
VL  - 24
UR  - https://doi.org/10.3390/ijms24021328
DO  - 10.3390/ijms24021328
AB  - Piper sarmentosum Roxb. (Piperaceae) is a traditional medicinal plant in South-East Asian countries. The chemical investigation of leaves from this species resulted in the isolation of three previously not described compounds, namely 4″-(3-hydroxy-3-methylglutaroyl)-2″-β-D-glucopyranosyl vitexin (1), kadukoside (2), and 6-O-trans-p-coumaroyl-D-glucono-1,4-lactone (3), together with 31 known compounds. Of these known compounds, 21 compounds were isolated for the first time from P. sarmentosum. The structures were established by 1D and 2D NMR techniques and HR-ESI-MS analyses. The compounds were evaluated for their anthelmintic (Caenorhabditis elegans), antifungal (Botrytis cinerea, Septoria tritici and Phytophthora infestans), antibacterial (Aliivibrio fischeri) and cytotoxic (PC-3 and HT-29 human cancer cells lines) activities. Methyl-3-(4-methoxyphenyl)propionate (8), isoasarone (12), and trans-asarone (15) demonstrated anthelmintic activity with IC50 values between 0.9 and 2.04 mM. Kadukoside (2) was most active against S. tritici with IC50 at 5.0 µM and also induced 94% inhibition of P. infestans growth at 125 µM. Trans-asarone (15), piperolactam A (23), and dehydroformouregine (24) displayed a dose-dependent effect against B. cinerea from 1.5 to 125 µM up to more than 80% inhibition. Paprazine (19), cepharadione A (21) and piperolactam A (23) inhibited bacterial growth by more than 85% at 100 µM. Only mild cytotoxic effects were observed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 221
TI  - Application of one‐step inner‐recycling counter‐current chromatography for the preparative separation and purification of chemical constituents from the rhizome of Bergenia ciliate (haw.) Sternb
JO  - J Sep Sci
PY  - 2023
SP  - 2300306
AU  - Aziz, S.
AU  - Akhter, F.
AU  - Hussain, H.
AU  - Liu, J.
AU  - Yan, H.
AU  - Cui, L.
AU  - Chen, Q.
AU  - Cheng, W.
AU  - Wang, D.
AU  - Wang, X.
AU  - 
VL  - 46
UR  - https://doi.org/10.1002/jssc.202300306
DO  - 10.1002/jssc.202300306
AB  - Bergenia ciliata (haw.) Sternb, the renowned pharmaceutical plant in Jammu and Kashmir of Pakistan, is widely applied in treating different illnesses including diabetes, diarrhea, and vomiting. This work employed an efficient one‐step inner‐recycling counter‐current chromatography for preparative separating and purifying compounds with similar partition coefficients from the rhizome of Bergenia ciliate (haw.). Five compounds, including quercetin rhamnodiglucoside (1), quercetin‐3‐O‐rutinoside (2), bergenine (3), kaempferol (4), and palmatic acid (5), were successfully separated using the optimized biphasic solvent system that contained ter‐butylmetylether/n‐butanol/acetonitrile/water (2:2:1:5, v/v) with the purities over 98%. Mass spectrometry and nuclear magnetic resonance were conducted for structural identification. As a result, our proposed strategy might be applied in separating compounds with similar partition coefficients, which was advantageous with regard to the less solvent and time consumption, and the increased number of theoretical plates.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 218
TI  - Lehmanniaside, a new cycloartane triterpene glycoside from Astragalus lehmannianus
JO  - Nat. Prod. Res.
PY  - 2023
SP  - 354-359
AU  - Agzamova, M. A.
AU  - Mamadalieva, N. Z.
AU  - Porzel, A.
AU  - Hussain, H.
AU  - Dube, M.
AU  - Franke, K.
AU  - Janibekov, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 37
UR  - https://doi.org/10.1080/14786419.2021.1969563
DO  - 10.1080/14786419.2021.1969563
AB  - Chemical investigation of the aerial parts of Astragalus lehmannianus
 Bunge (Leguminosae) led to the isolation and identification of a new 
cycloartane triterpene glycoside – lehmanniaside (2\'-O-acetyl-3-β-O-D-xylopyranosyl-3β,6α,16β,24α-tetrahydroxy-20,25-epoxycycloartane).
 Its structure was elucidated by means of spectroscopic analysis (HR-MS,
 1D and 2D NMR). Bioassays showed that lehmanniaside exhibits weak 
anthelmintic, antifungal, and cytotoxic activities.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 216
TI  - Allosteric crosstalk in modular proteins: Function fine-tuning and drug design
JO  - Comp Struct Biotechnol J
PY  - 2023
SP  - 5003-5015
AU  - Abhishek, S.
AU  - Deeksha, W.
AU  - Nethravathi, K. R.
AU  - Davari, M. D.
AU  - Rajakumara, E.
AU  - 
VL  - 21
UR  - https://doi.org/10.1016/j.csbj.2023.10.013
DO  - 10.1016/j.csbj.2023.10.013
AB  - Modular proteins are regulatory proteins that carry out more than one function. These proteins upregulate or downregulate a biochemical cascade to establish homeostasis in cells. To switch the function or alter the efficiency (based on cellular needs), these proteins require different facilitators that bind to a site different from the catalytic (active/orthosteric) site, aka ‘allosteric site’, and fine-tune their function. These facilitators (or effectors) are allosteric modulators. In this Review, we have discussed the allostery, characterized them based on their mechanisms, and discussed how allostery plays an important role in the activity modulation and function finetuning of proteins. Recently there is an emergence in the discovery of allosteric drugs. We have also emphasized the role, significance, and future of allostery in therapeutic applications.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 215
TI  - Dissection of Moringa oleifera leaf metabolome in context of its different extracts, origin and in relationship to its biological effects as analysed using molecular networking and chemometrics
JO  - Food Chem.
PY  - 2023
SP  - 133948
AU  - Abdel Shakour, Z. T.
AU  - El-Akad, R. H.
AU  - Elshamy, A. I.
AU  - El Gendy, A. E.-N. G.
AU  - Wessjohann, L. A.
AU  - Farag, M. A.
AU  - 
VL  - 399
UR  - https://doi.org/10.1016/j.foodchem.2022.133948
DO  - 10.1016/j.foodchem.2022.133948
AB  - M. oleifera known as “miracle tree” is increasingly used in nutraceuticals for the reported health effects and nutritional value of its leaves. This study presents the first metabolome profiling of M. oleifera leaves of African origin using different solvent polarities via HR-UPLC/MS based molecular networking followed by multivariate data analyses for samples classification. 119 Chemicals were characterized in both positive and negative modes belonging to 8 classes viz. phenolic acids, flavonoids, peptides, fatty acids/amides, sulfolipids, glucosinolates and carotenoids. New metabolites i.e., polyphenolics, fatty acids, in addition to a new class of sulfolipids were annotated for the first time in Moringa leaves. In vitro anti-inflammatory and anti-aging bioassays of the leaf extracts were assessed and in correlation to their metabolite profile via multivariate data analyses. Kaempferol, quercetin and apigenin-O/C-glycosides, fatty acyl amides and carotenoids appeared crucial for biological activities and leaves origin discrimination.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2511
TI  - A hybrid model combining evolutionary probability and machine learning leverages data-driven protein engineering
JO  - bioRxiv
PY  - 2022
SP  - 
AU  - Illig, A.-M.
AU  - Siedhoff, N. E.
AU  - Schwaneberg, U.
AU  - Davari, M. D.
AU  - 
VL  - 
UR  - https://doi.org/10.1101/2022.06.07.495081
DO  - 10.1101/2022.06.07.495081
AB  - Protein engineering through directed evolution and (semi-)rational approaches has been applied successfully to optimize protein properties for broad applications in molecular biology, biotechnology, and biomedicine. The potential of protein engineering is not yet fully realized due to the limited screening throughput hampering the efficient exploration of the vast protein sequence space. Data-driven strategies have emerged as a powerful tool to leverage protein engineering by providing a model of the sequence-fitness landscape that can exhaustively be explored in silico and capitalize on the high diversity potential offered by nature However, as both the quality and quantity of the inputted data determine the success of such approaches, the applicability of data-driven strategies is often limited due to sparse data. Here, we present a hybrid model that combines direct coupling analysis and machine learning techniques to enable data-driven protein engineering when only few labeled sequences are available. Our method achieves high performance in predicting a protein’s fitness based on its sequence regardless of the number of sequences-fitness pairs in the training dataset. Besides reducing the computational effort compared to state-of-the-art methods, it outperforms them for sparse data situations, i.e., 50 − 250 labeled sequences available for training. In essence, the developed method is auspicious for data-driven protein engineering, especially for protein engineers who have only access to a limited amount of data for sequence-fitness landscape modeling.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 395
TI  - An efficient high‐speed counter‐current chromatography method for the preparative separation of potential antioxidant from
            Paeonia lactiflora
            Pall. combination of in vitro evaluation and molecular docking
JO  - J Sep Sci
PY  - 2022
SP  - 1856-1865
AU  - Sun, X.
AU  - Chen, L.
AU  - Yan, H.
AU  - Cui, L.
AU  - Hussain, H.
AU  - Xie, L.
AU  - Liu, J.
AU  - Jiang, Y.
AU  - Meng, Z.
AU  - Cao, G.
AU  - Park, J.
AU  - Wang, D.
AU  - 
VL  - 45
UR  - https://doi.org/10.1002/jssc.202200082
DO  - 10.1002/jssc.202200082
AB  - Paeonia lactiflora Pall., one of the most famous classical herbal medicine, has been used to treat diseases for over 1200 years. In this research, the functional ingredients were purified by online-switch two-dimensional high-speed counter-current chromatography combined with inner-recycling and continuous injection mode. The antioxidant activity was evaluated by investigating the 2,2’-azobis (2-amidinopropane) dihydrochloride-induced oxidant damage in vitro and confirmed through molecular docking. n-Butanol/ethyl acetate/water (2:3:5, v/v) solvent system was used for the first dimensional separation and optimized the sample loading. Two pure compounds and a polyphenol-enriched fraction were separated. The polyphenol-enriched fraction was separated with a solvent system n-hexane/ethyl acetate/methanol/water (2:8:4:6, v/v) with continuous injection mode. Five compounds were successfully separated, including gallic acid (1), methyl gallate (2), albiflorin (3), paeoniflorin (4), and ethyl gallate (5). Their structures were identified by mass spectrometry and nuclear magnetic resonance. The results from antioxidant effect showed that albiflorin had stronger antioxidant activity. Molecular docking results indicated that the affinity energy of the identified compounds ranged from -3.79 to -8.22 kcal/mol and albiflorin showed the lowest affinity energy. Overall, all those findings suggested that the strong antioxidant capacity of albiflorin can be potentially used for treatment of diseases that caused by oxidation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 393
TI  - Dynamics of Reactive Carbonyl Species in Pea Root Nodules in Response to Polyethylene Glycol (PEG)-Induced Osmotic Stress
JO  - Int. J. Mol. Sci.
PY  - 2022
SP  - 2726
AU  - Soboleva, A.
AU  - Frolova, N.
AU  - Bureiko, K.
AU  - Shumilina, J.
AU  - Balcke, G. U.
AU  - Zhukov, V. A.
AU  - Tikhonovich, I. A.
AU  - Frolov, A.
AU  - 
VL  - 23
UR  - https://doi.org/10.3390/ijms23052726
DO  - 10.3390/ijms23052726
AB  - Drought dramatically affects crop productivity worldwide. For legumes this effect is especially pronounced, as their symbiotic association with rhizobia is highly-sensitive to dehydration. This might be attributed to the oxidative stress, which ultimately accompanies plants’ response to water deficit. Indeed, enhanced formation of reactive oxygen species in root nodules might result in up-regulation of lipid peroxidation and overproduction of reactive carbonyl compounds (RCCs), which readily modify biomolecules and disrupt cell functions. Thus, the knowledge of the nodule carbonyl metabolome dynamics is critically important for understanding the drought-related losses of nitrogen fixation efficiency and plant productivity. Therefore, here we provide, to the best of our knowledge, for the first time a comprehensive overview of the pea root nodule carbonyl metabolome and address its alterations in response to polyethylene glycol-induced osmotic stress as the first step to examine the changes of RCC patterns in drought treated plants. RCCs were extracted from the nodules and derivatized with 7-(diethylamino)coumarin-3-carbohydrazide (CHH). The relative quantification of CHH-derivatives by liquid chromatography-high resolution mass spectrometry with a post-run correction for derivative stability revealed in total 194 features with intensities above 1 × 105 counts, 19 of which were down- and three were upregulated. The upregulation of glyceraldehyde could accompany non-enzymatic conversion of glyceraldehyde-3-phosphate to methylglyoxal. The accumulation of 4,5-dioxovaleric acid could be the reason for down-regulation of porphyrin metabolism, suppression of leghemoglobin synthesis, inhibition of nitrogenase and degradation of legume-rhizobial symbiosis in response to polyethylene glycol (PEG)-induced osmotic stress effect. This effect needs to be confirmed with soil-based drought models.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 392
TI  - Seed-to-seedling transition in Pisum sativum L.: A transcriptomic approach
JO  - Plants
PY  - 2022
SP  - 1686
AU  - Smolikova, G.
AU  - Strygina, K.
AU  - Krylova, E.
AU  - Vikhorev, A.
AU  - Bilova, T.
AU  - Frolov, A.
AU  - Khlestkina, E.
AU  - Medvedev, S.
AU  - 
VL  - 11
UR  - https://doi.org/10.3390/plants11131686
DO  - 10.3390/plants11131686
AB  - The seed-to-seedling transition is a crucial step in the plant life cycle. The transition occurs at the end of seed germination and corresponds to the initiation of embryonic root growth. To improve our understanding of how a seed transforms into a seedling, we germinated the Pisum sativum L. seeds for 72 h and divided them into samples before and after radicle protrusion. Before radicle protrusion, seeds survived after drying and formed normally developed seedlings upon rehydration. Radicle protrusion increased the moisture content level in seed axes, and the accumulation of ROS first generated in the embryonic root and plumule. The water and oxidative status shift correlated with the desiccation tolerance loss. Then, we compared RNA sequencing-based transcriptomics in the embryonic axes isolated from pea seeds before and after radicle protrusion. We identified 24,184 differentially expressed genes during the transition to the post-germination stage. Among them, 2101 genes showed more prominent expression. They were related to primary and secondary metabolism, photosynthesis, biosynthesis of cell wall components, redox status, and responses to biotic stress. On the other hand, 415 genes showed significantly decreased expression, including the groups related to water deprivation (eight genes) and response to the ABA stimulus (fifteen genes). We assume that the water deprivation group, especially three genes also belonging to ABA stimulus (LTI65, LTP4, and HVA22E), may be crucial for the desiccation tolerance loss during a metabolic switch from seed to seedling. The latter is also accompanied by the suppression of ABA-related transcription factors ABI3, ABI4, and ABI5. Among them, HVA22E, ABI4, and ABI5 were highly conservative in functional domains and showed homologous sequences in different drought-tolerant species. These findings elaborate on the critical biochemical pathways and genes regulating seed-to-seedling transition.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 390
TI  - Synthesis and characterization of novel hydrazone derivatives of isonicotinic hydrazide and their evaluation for antibacterial and cytotoxic potential
JO  - Molecules
PY  - 2022
SP  - 6770
AU  - Shah, M. A.
AU  - Uddin, A.
AU  - Shah, M. R.
AU  - Ali, I.
AU  - Ullah, R.
AU  - Hannan, P. A.
AU  - Hussain, H.
AU  - 
VL  - 27
UR  - https://doi.org/10.3390/molecules27196770
DO  - 10.3390/molecules27196770
AB  - Hydrazones are active compounds having an azomethine –NHN=CH group and are widely studied owing to their ease of preparation and diverse pharmacological benefits. Novel isonicotinic hydrazone derivatives of vanillin aldehyde and salicyl aldehyde were synthesized that had azomethine linkages and were characterized by UV–Visible, FTIR, EI-MS, 1H-NMR and 13C-NMR spectroscopy. The compounds were screened for their antibacterial activity against Staphylococcus aureus, Bacillus subtilus, and Escherichia coli using disc diffusion and minimum inhibitory concentration (MIC) methods. For cytotoxicity, a brine shrimp lethality test was performed to calculate the lethal concentration (LC50). The results demonstrated appreciable antibacterial activities against the applied strains, amongst which the compounds coded NH3 and NH5 showed maximum inhibition and MIC responses. In terms of cytotoxic activity, the maximum effect was observed in compound NH5 and NH6 treatments with minimum survival percentages of 36.10 ± 3.45 and 32.44 ± 2.0, respectively. These hydrazones could be potential candidates in antitumorigenic therapy against various human cancer cells.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 387
TI  - Structure and cooperativity in substrate–enzyme interactions: Perspectives on enzyme engineering and inhibitor design
JO  - ACS Chem. Biol.
PY  - 2022
SP  - 266-280
AU  - Rajakumara, E.
AU  - Abhishek, S.
AU  - Nitin, K.
AU  - Saniya, D.
AU  - Bajaj, P.
AU  - Schwaneberg, U.
AU  - Davari, M. D.
AU  - 
VL  - 17
UR  - https://doi.org/10.1021/acschembio.1c00500
DO  - 10.1021/acschembio.1c00500
AB  - Enzyme-based synthetic chemistry provides a green way to synthesize industrially important chemical scaffolds and provides incomparable substrate specificity and unmatched stereo-, regio-, and chemoselective product formation. However, using biocatalysts at an industrial scale has its challenges, like their narrow substrate scope, limited stability in large-scale one-pot reactions, and low expression levels. These limitations can be overcome by engineering and fine-tuning these biocatalysts using advanced protein engineering methods. A detailed understanding of the enzyme structure and catalytic mechanism and its structure–function relationship, cooperativity in binding of substrates, and dynamics of substrate–enzyme–cofactor complexes is essential for rational enzyme engineering for a specific purpose. This Review covers all these aspects along with an in-depth categorization of various industrially and pharmaceutically crucial bisubstrate enzymes based on their reaction mechanisms and their active site and substrate/cofactor-binding site structures. As the bisubstrate enzymes constitute around 60% of the known industrially important enzymes, studying their mechanism of actions and structure–activity relationship gives significant insight into deciding the targets for protein engineering for developing industrial biocatalysts. Thus, this Review is focused on providing a comprehensive knowledge of the bisubstrate enzymes’ structure, their mechanisms, and protein engineering approaches to develop them into industrial biocatalysts.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 385
TI  - Polyoxygenated cyclohexenes from Uvaria grandiflora with multi-enzyme targeting properties relevant in Type 2 Diabetes and Obesity
JO  - ACS Omega
PY  - 2022
SP  - 36856-36864
AU  - Quimque, M. T. J.
AU  - Magsipoc, R. J. Y.
AU  - Llames, L. C. J.
AU  - Flores, A. I. G.
AU  - Garcia, K. Y. M.
AU  - Ratzenböck, A.
AU  - Hussain, H.
AU  - Macabeo, A. P. G.
AU  - 
VL  - 7
UR  - https://doi.org/10.1021/acsomega.2c05544
DO  - 10.1021/acsomega.2c05544
AB  - Shikimic acid-derived polyoxygenated cyclohexene natural products commonly occurring in several species of the Uvaria represent natural products with promising biological activities. While a number of derivatives have been reported from Uvaria grandiflora (U. grandiflora), further studies are needed to discover additional bioactive congeners, particularly derivatives with multi-protein tarUvaria grandiflora (U. grandiflora)Uvaria grandiflora (U. grandiflora)d in diseases such as diabetes and obesity. In this paper, isolation and identification of a new highly oxygenated cyclohexene, uvagrandol (1), along with the known compound (-)-zeylenone (2) from the DCM sub-extract of U. grandiflora following in vitro and in silico assessment of their enzyme inhibitory properties against α-glucosidase, dipeptidyl peptidase IV, porcine lipase, and human recombinant monoacylglycerol lipase are reported. The structure of 1 was elucidated using 1D and 2D NMR data analysis. The absolute configuration of 1 was established by quantum chemical calculations via the Gauge-Independent Atomic Orbital (GIAO) NMR method followed by TDDFT-Electronic Circular Dichroism (ECD) calculations. The structures of the eight possible stereoisomers were optimized by means of DFT calculations (B3LYP/6-31+G[d,p] in vacuum), and then their isotropic shielding tensors were obtained using the GIAO method at mPW1PW91/6-31G(d,p) in chloroform. Through DP4+, the isomer of configuration (1S,2S,3R,6R) for 1 was predicted with 96.3% probability. Compounds 1 and 2 significantly inhibited the four target enzymes in vitro. Binding studies through molecular docking simulations showed strong binding affinities for (-)-zeylenone (2), thus validating the in vitro results. Our findings suggest the potential of polyoxygenated cyclohexenes, in particular (-)-zeylenone (2), in anti-diabetic and anti-obesity drug discovery.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 384
TI  - Mesoporous silica nanoparticles enhance the anticancer efficacy of platinum(IV)-phenolate conjugates in breast cancer cell lines
JO  - Nanomaterials
PY  - 2022
SP  - 3767
AU  - Predarska, I.
AU  - Saoud, M.
AU  - Drača, D.
AU  - Morgan, I.
AU  - Komazec, T.
AU  - Eichhorn, T.
AU  - Mihajlović, E.
AU  - Dunđerović, D.
AU  - Mijatović, S.
AU  - Maksimović-Ivanić, D.
AU  - Hey-Hawkins, E.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 12
UR  - https://doi.org/10.3390/nano12213767
DO  - 10.3390/nano12213767
AB  - The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin include drug resistance and significant side effects. Due to their better stability, as well as the possibility to introduce biologically active ligands in their axial positions constructing multifunctional prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations. Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV) conjugates demonstrated higher or comparable activity with respect to cisplatin against different human breast cancer cell lines, while upon immobilization, superior antiproliferative activity with markedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin was observed. Mechanistic investigations with the most potent conjugate, cisplatin-diacetyl caffeate (1), and the corresponding MSNs (SBA-15&#124;1) in a 4T1 mouse breast cancer cell line showed that these compounds induce apoptotic cell death causing strong caspase activation. In vivo, in BALB/c mice, 1 and SBA-15&#124;1 inhibited the tumor growth while decreasing the necrotic area and lowering the mitotic rate.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 383
TI  - Cisplatin−cyclooxygenase inhibitor conjugates, free and immobilised in mesoporous silica SBA-15, prove highly potent against triple-negative MDA-MB-468 breast cancer cell line
JO  - Dalton Trans.
PY  - 2022
SP  - 857–869
AU  - Predarska, I.
AU  - Saoud, M.
AU  - Morgan, I.
AU  - Eichhorn, T.
AU  - Kaluđerović, G. N.
AU  - Hey-Hawkins, E.
AU  - 
VL  - 51
UR  - https://doi.org/10.1039/D1DT03265H
DO  - 10.1039/d1dt03265h
AB  - For the development of anticancer drugs with higher activity and reduced
 toxicity, two approaches were combined: preparation of platinum(IV) complexes exhibiting higher stability compared to their platinum(II)
 counterparts and loading them into mesoporous silica SBA-15 with the 
aim to utilise the passive enhanced permeability and retention (EPR) 
effect of nanoparticles for accumulation in tumour tissues. Three 
conjugates based on a cisplatin scaffold bearing the anti-inflammatory 
drugs naproxen, ibuprofen or flurbiprofen in the axial positions (1, 2 and 3, respectively) were synthesised and loaded into SBA-15 to afford the mesoporous silica nanoparticles (MSNs) SBA-15&#124;1, SBA-15&#124;2 and SBA-15&#124;3.
 Superior antiproliferative activity of both free and immobilised 
conjugates in a panel of four breast cancer cell lines (MDA-MB-468, 
HCC1937, MCF-7 and BT-474) with markedly increased cytotoxicity with 
respect to cisplatin was demonstrated. All compounds exhibit highest 
activity against the triple-negative cell line MDA-MB-468, with 
conjugate 1 being the most potent. However, against MCF-7 and BT-474 cell lines, the most notable improvement was found, with IC50
 values up to 240-fold lower than cisplatin. Flow cytometry assays 
clearly show that all compounds induce apoptotic cell death elevating 
the levels of both early and late apoptotic cells. Furthermore, 
autophagy as well as formation of reactive oxygen species (ROS) and 
nitric oxide (NO) were elevated to a similar or greater extent than with
 cisplatin.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 381
TI  - How does surface charge engineering of Bacillus subtilis lipase A improve ionic liquid resistance? Lessons learned from molecular dynamics simulations
JO  - ACS Sustainable Chemistry &amp; Engineering
PY  - 2022
SP  - 2689-2698
AU  - Pramanik, S.
AU  - Cui, H.
AU  - Dhoke, G. V.
AU  - Yildiz, C. B.
AU  - Vedder, M.
AU  - Jaeger, K.-E.
AU  - Schwaneberg, U.
AU  - Davari, M. D.
AU  - 
VL  - 10
UR  - https://doi.org/10.1021/acssuschemeng.1c07332
DO  - 10.1021/acssuschemeng.1c07332
AB  - Biocatalysis in ionic liquids (ILs) gained substantial interest due to solvent properties of the ILs, such as near-zero vapor pressure, high thermal stability, and wide tunability. Enzymes are often not catalytically active in ILs; therefore, understanding and improving enzyme resistance in ILs are essential to enable efficient biocatalysis in ionic liquids. Surface charge engineering has repeatedly been reported to enhance enzyme resistance toward ILs. However, the molecular knowledge about how substitutions to charged amino acids improve enzyme activity in an IL is far from being understood. Here, we report a comprehensive study to provide some principles of how surface charged amino acid substitutions (negatively and positively) strengthen the IL resistance of the Bacillus subtilis lipase A (BSLA) in [BMIM]Cl. Twenty typical BSLA substitutions (ten beneficial and ten nonbeneficial, obtained from the BSLA-SSM library) were studied by molecular dynamics (MD) simulations in the [BMIM]Cl system. The BSLA-IL interaction patterns were printed by analyzing several structural- and solvation-based observables. Lessons learned by analyzing the SSM library of BSLA comprise the following: (i) A general trend was found where both negatively and positively charged substitutions increased the essential water molecules locally at the substitution site, thereby contributing to the overall protein hydration shell. (ii) Electrostatic repulsion of both IL ions and the refined hydration shell are ultimately the two main drivers to enhanced IL resistance. The analysis of 20 BSLA substitutions and the identified common interactions reveals that surface charge engineering is very likely to be a general protein engineering strategy to enhance lipase/enzyme activity in ILs. Moreover, this study also suggests that MD is a valuable technique to screen for beneficial substitutions that repel/recruit surface solvation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 380
TI  - Optimized hemolysin Type 1 secretion system in
            Escherichia coli
            by directed evolution of the Hly enhancer fragment and including a terminator region
JO  - ChemBioChem
PY  - 2022
SP  - e202100702
AU  - Pourhassan N., Z.
AU  - Cui, H.
AU  - Khosa, S.
AU  - Davari, M. D.
AU  - Jaeger, K.
AU  - Smits, S. H. J.
AU  - Schwaneberg, U.
AU  - Schmitt, L.
AU  - 
VL  - 23
UR  - https://doi.org/10.1002/cbic.202100702
DO  - 10.1002/cbic.202100702
AB  - Type 1 secretion systems (T1SS) have a relatively simple architecture compared to other classes of secretion systems and therefore, are attractive to be optimized by protein engineering. Here, we report a KnowVolution campaign for the hemolysin (Hly) enhancer fragment, an untranslated region upstream of the hlyA gene, of the hemolysin T1SS of Escherichia coli to enhance its secretion efficiency. The best performing variant of the Hly enhancer fragment contained five nucleotide mutations at  five positions (A30U, A36U, A54G, A81U, and A116U) resulted in a 2-fold increase in the secretion level of a model lipase fused to the secretion carrier HlyA1. Computational analysis suggested that altered affinity to the generated enhancer fragment towards the S1 ribosomal protein contributes to the enhanced secretion levels. Furthermore, we demonstrate that involving a native terminator region along with the generated Hly enhancer fragment increased the secretion levels of the Hly system up to 5-fold.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 378
TI  - NMR metabolome-based classification of Cymbopogon Species: a prospect for phyto-equivalency of its different accessions using chemometric tools
JO  - Food Analytical Methods
PY  - 2022
SP  - 2095-2106
AU  - Otify, A. M.
AU  - Serag, A.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - Farag, M. A.
AU  - 
VL  - 15
UR  - https://doi.org/10.1007/s12161-022-02257-8
DO  - 10.1007/s12161-022-02257-8
AB  - Cymbopogon species are widely distributed worldwide and known for their high essential oil content with potential commercial and medicinal benefits justifying for their inclusion in food and cosmetics. Most species received scant characterization regarding their full complement of bioactive constituents necessary to explain their medicinal activities. In this study, the metabolite profiles of 5 Cymbopogon species, C. citratus, C. flexuosus, C. procerus, C. martini, and C. nardus, were characterized via NMR-based metabolomics. The results of 13 shoot accessions revealed the identification and quantification of 23 primary and secondary metabolites belonging to various compound classes. Multivariate analyses were used for species classification, though found not successful in discrimination based on geographical origin. Nevertheless, C. citratus was found particularly enriched in neral, geranial, (E)-aconitic acid, isoorientin, and caffeic acid as the major characterizing metabolites compared to other species, while an unknown apigenin derivative appeared to discriminate C. martini. The high essential oil and phenolic content in C. citratus emphasizes its strong antioxidant activity, whereas (E)-aconitic acid accounts for its traditional use as insecticide. This study affords the first insight into metabolite compositional differences among Cymbopogon species. Moreover, antimicrobial, insecticidal, antidiabetic, and antioxidant compounds were identified that can be utilized as biomarkers for species authentication.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 377
TI  - Phytochemical characterization of water avens (Geum rivale L.) Extracts: Structure assignment and biological activity of the major phenolic constituents
JO  - Plants
PY  - 2022
SP  - 2859
AU  - Orlova, A.
AU  - Kysil, E.
AU  - Tsvetkova, E.
AU  - Meshalkina, D.
AU  - Whaley, A.
AU  - Whaley, A. O.
AU  - Laub, A.
AU  - Francioso, A.
AU  - Babich, O.
AU  - Wessjohann, L. A.
AU  - Mosca, L.
AU  - Frolov, A.
AU  - Povydysh, M.
AU  - 
VL  - 11
UR  - https://doi.org/10.3390/plants11212859
DO  - 10.3390/plants11212859
AB  - Water avens (Geum rivale L.) is a common Rosaceae plant widely spread in Europe and North America. It is rich in biologically active natural products, some of which are promising as prospective pharmaceuticals. The extracts of water avens are well known for their triterpenoid metabolites and associated anti-inflammatory, antimicrobial and antioxidant activities. However, the polyphenolic profiles of G. rivale L. are still awaiting complete characterization. Accordingly, the contribution of its individual components to the antioxidant, antibacterial and neuroprotective activity of the extracts is still unknown. As this plant can be available on an industrial scale, a better knowledge of its properly-relevant constituents might give access to new highly-efficient pharmaceutical substances and functional products. Therefore, herein we comprehensively characterize the secondary metabolome of G. rivale by ESI-HR-MS, ESI-HR-MSn and NMR spectroscopy with a special emphasis on the polyphenolic composition of its aerial parts. Furthermore, a multilateral evaluation of the antioxidant, neuroprotective and antibacterial properties of the aqueous and ethyl acetate fractions of the total aqueous alcoholic extract as well as individual isolated polyphenols was accomplished. Altogether four phenolic acid derivatives (trigalloyl hexose, caffeoyl-hexoside malate, ellagic acid and ellagic acid pentoside), six flavonoids (three quercetin derivatives, kaempferol and three its derivatives and two isorhamnetin derivatives) and four tannins (HHDP-hexoside, proantocyanidin dimer, pedunculagin I and galloyl-bis-HHDP-hexose) were identified in this plant for the first time. The obtained aqueous and ethyl acetate fractions of the total extract as well as the isolated individual compounds showed pronounced antioxidant activity. In addition, a pronounced antibacterial activity against several strains was proved for the studied fractions (for ethyl acetate fraction the highest activity against E. coli АТСС 25922 and S. aureus strains ATCC 27853 and SG-511 (MIC 15.6 μg/mL) was observed; for aqueous fraction—against Staphylococcus aureus SG-511 (MIC 31.2 μg/mL)). However, the anti-neurodegenerative (neuroprotective) properties could not be found with the employed methods. However, the antibacterial activity of the fractions could not be associated with any of the isolated individual major phenolics (excepting 3-O-methylellagic acid). Thus, the aerial parts of water avens represent a promising source of polyphenolic compounds with antioxidant activity and therefrom derived human health benefits, although the single constituents isolated so far lack a dominant selectively bioactive constituent in the bioassays performed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 376
TI  - Bacterial-type ferroxidase tunes iron-dependent phosphate sensing during Arabidopsis root development
JO  - Curr. Biol.
PY  - 2022
SP  - 2189-2205
AU  - Naumann, C.
AU  - Heisters, M.
AU  - Brandt, W.
AU  - Janitza, P.
AU  - Alfs, C.
AU  - Tang, N.
AU  - Toto Nienguesso, A.
AU  - Ziegler, J.
AU  - Imre, R.
AU  - Mechtler, K.
AU  - Dagdas, Y.
AU  - Hoehenwarter, W.
AU  - Sawers, G.
AU  - Quint, M.
AU  - Abel, S.
AU  - 
VL  - 32
UR  - https://doi.org/10.1016/j.cub.2022.04.005
DO  - 10.1016/j.cub.2022.04.005
AB  - Access to inorganic phosphate (Pi), a principal intermediate of energy and nucleotide metabolism, profoundly affects cellular activities and plant performance. In most soils, antagonistic Pi-metal interactions restrict Pi bioavailability, which guides local root development to maximize Pi interception. Growing root tips scout the essential but immobile mineral nutrient; however, the mechanisms monitoring external Pi sta-tus are unknown. Here, we show that Arabidopsis LOW PHOSPHATE ROOT 1 (LPR1), one key determinant of Fe-dependent Pi sensing in root meristems, encodes a novel ferroxidase of high substrate specificity and affinity (apparent KM   ∼2 μmM Fe2+). LPR1 typifies an ancient, Fe-oxidizing multicopper protein family that evolved early upon bacterial land colonization. The ancestor of streptophyte algae and embryophytes (land plants) acquired LPR1-type ferroxidase from soil bacteria via horizontal gene transfer, a hypothesis supported by phylogenomics, homology modeling, and biochemistry. Our molecular and kinetic data on LPR1 regulation indicate that Pi-dependent Fe substrate availability determines LPR1 activity and function. Guided by the metabolic lifestyle of extant sister bacterial genera, we propose that Arabidopsis LPR1 monitors subtle concentration differentials of external Fe availability as a Pi-dependent cue to adjust root meristem maintenance via Fe redox signaling and cell wall modification. We further hypothesize that the acquisition of bacterial LPR1-type ferroxidase by embryophyte progenitors facilitated the evolution of local Pi sensing and acquisition during plant terrestrialization.
A2  - 
C1  - Bioorganic Chemistry; Molecular Signal Processing
ER  - 


TY  - JOUR
ID  - 374
TI  - Structural elucidation of an atropisomeric entcassiflavan-(4β→8)-epicatechin isolated from Dalbergia monetaria L.f. based on NMR and ECD calculations in comparison to experimental data
JO  - Molecules
PY  - 2022
SP  - 2512
AU  - Moura, P. H. B.
AU  - Brandt, W.
AU  - Porzel, A.
AU  - Martins, R. C. C.
AU  - Leal, I. C. R.
AU  - Wessjohann, L. A.
AU  - 
VL  - 27
UR  - https://doi.org/10.3390/molecules27082512
DO  - 10.3390/molecules27082512
AB  - A rare dihydoxyflavan-epicatechin proanthocyanidin, entcassiflavan-(4β→8)-epicatechin, was isolated from Dalbergia monetaria, a plant widely used by traditional people from the Amazon to treat urinary tract infections. The constitution and relative configuration of the compound were elucidated by HR-MS and detailed 1D- and 2D-NMR measurements. By comparing the experimental electronic circular dichroism (ECD) spectrum with the calculated ECD spectra of all 16 possible isomers, the absolute configuration, the interflavan linkage, and the atropisomers could be determined.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 372
TI  - Substituent-driven selective N-/O-alkylation of 4-(trihalomethyl)pyrimidin-2(1H)-ones using brominated enones
JO  - J. Org. Chem.
PY  - 2022
SP  - 4590-4602
AU  - Mittersteiner, M.
AU  - Pereira, G. S.
AU  - Silva, Y.
AU  - Wessjohann, L. A.
AU  - Bonacorso, H. G.
AU  - Martins, M. A. P.
AU  - Zanatta, N.
AU  - 
VL  - 87
UR  - https://doi.org/10.1021/acs.joc.1c02919
DO  - 10.1021/acs.joc.1c02919
AB  - The selective N- or O-alkylation of 4-(trihalomethyl)-pyrimidin-2(1H)-ones, using 5-bromo enones/enaminones as alkylating agents, is reported. It was found that the selectivity toward the N-or O-regioisomer is driven by the substituent present at the 6-position of the pyrimidine ring, thus enabling the preparation of each isomer as the sole product, in 60−95% yields. Subsequent cyclocondensation of the enaminone moiety with nitrogen dinucleophiles led to pyrimidine−azole conjugates in 55−83% yields.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 371
TI  - Chemoselective O-alkylation of 4-(trifluoromethyl)pyrimidin-2(1H)-ones using 4-(iodomethyl)pyrimidines
JO  - ACS Omega
PY  - 2022
SP  - 18930-18939
AU  - Mittersteiner, M.
AU  - Pereira, G. S.
AU  - Wessjohann, L. A.
AU  - Bonacorso, H. G.
AU  - Martins, M. A. P.
AU  - Zanatta, N.
AU  - 
VL  - 7
UR  - https://doi.org/10.1021/acsomega.2c01925
DO  - 10.1021/acsomega.2c01925
AB  - This study reports two strategies for preparing O-alkyl derivatives of 6-substituted-4-(trifluoromethyl)pyrimidin-(1H)-ones: a linear protocol of alkylation,using a CCC-building block followed by [3 + 3]-type cyclocondensation with 2-methylisothiourea sulfate and a convergent protocol based on direct alkylation, using 4-(iodomethyl)-2-(methylthio)-6-(trihalomethyl)pyrimidines. It was found that thecyclocondensation strategy is not feasible; thus, the direct chemoselective O-alkylationwas performed, and 18 derivatives of the targeted pyrimidines were obtained in 70−98%yields. The structure of the products was unambiguously determined via single crystal X-ray analyses and two-dimensional nuclear magnetic resonance experiments.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 369
TI  - Chemical synthesis of trans 8-methyl-6-nonenoyl-CoA and functional expression unravel capsaicin synthase activity encoded by the Pun1 Locus
JO  - Molecules
PY  - 2022
SP  - 6878
AU  - Milde, R.
AU  - Schnabel, A.
AU  - Ditfe, T.
AU  - Hoehenwarter, W.
AU  - Proksch, C.
AU  - Westermann, B.
AU  - Vogt, T.
AU  - 
VL  - 27
UR  - https://doi.org/10.3390/molecules27206878
DO  - 10.3390/molecules27206878
AB  - Capsaicin, produced by diverse Capsicum species, is among the world’s most popular spices and of considerable pharmaceutical relevance. Although the capsaicinoid biosynthetic pathway has been investigated for decades, several biosynthetic steps have remained partly hypothetical. Genetic evidence suggested that the decisive capsaicin synthase is encoded by the Pun1 locus. Yet, the genetic evidence of the Pun1 locus was never corroborated by functionally active capsaicin synthase that presumably catalyzes an amide bond formation between trans 8-methyl-6-nonenoyl-CoA derived from branched-chain amino acid biosynthesis and vanilloylamine derived from the phenylpropanoid pathway. In this report, we demonstrate the enzymatic activity of a recombinant capsaicin synthase encoded by Pun1, functionally expressed in Escherichia coli, and provide information on its substrate specificity and catalytic properties. Recombinant capsaicin synthase is specific for selected aliphatic CoA-esters and highly specific for vanilloylamine. Partly purified from E. coli, the recombinant active enzyme is a monomeric protein of 51 kDa that is independent of additional co-factors or associated proteins, as previously proposed. These data can now be used to design capsaicin synthase variants with different properties and alternative substrate preferences.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 368
TI  - The molecular basis and enzyme engineering strategies for improvement of coupling efficiency in cytochrome P450s
JO  - Biotechnol. Adv.
PY  - 2022
SP  - 108051
AU  - Meng, S.
AU  - Ji, Y.
AU  - Zhu, L.
AU  - Dhoke, G. V.
AU  - Davari, M. D.
AU  - Schwaneberg, U.
AU  - 
VL  - 61
UR  - https://doi.org/10.1016/j.biotechadv.2022.108051
DO  - 10.1016/j.biotechadv.2022.108051
AB  - Cytochrome P450s are heme-thiolate enzymes that have been broadly applied in pharmaceutical and biosynthesis because of their efficient oxidation at inert carbons. Extensive engineering campaigns are applied to P450s to explore new non-natural substrates and reactions; however, achieving high coupling efficiency is one of the main challenges. The undesirable uncoupling reactions result in the extra consumption of expensive cofactor NAD(P)H, and lead to the accumulation of reactive oxygen species and the inactivation of enzymes and organisms. Using protein engineering methods, these limitations can be overcome by engineering and fine-tuning P450s. A systemic perspective of the enzyme structure and the catalytic mechanism is essential for P450 engineering campaigns for higher coupling efficiency. This review provide an overview on factors contributing to uncoupling and protein engineering approaches to minimize uncoupling and thereby generating efficient and robust P450s for industrials use. Contributing uncoupling factors are classified into three main groups: i) substrate binding pocket; ii) ligand access tunnel(s); and iii) electron transfer pathway(s). Finally, we draw future directions for combinations of effective state-of-the-art technologies and available software/online tools for P450s engineering campaigns.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 367
TI  - Modulating the coupling efficiency of P450 BM3 by controlling water diffusion through access tunnel engineering
JO  - ChemSusChem
PY  - 2022
SP  - e202102434
AU  - Meng, S.
AU  - Ji, Y.
AU  - Liu, L.
AU  - Davari, M. D.
AU  - Schwaneberg, U.
AU  - 
VL  - 15
UR  - https://doi.org/10.1002/cssc.202102434
DO  - 10.1002/cssc.202102434
AB  - Cytochrome P450s has gained the great interest for their broad  substrate  scope  in the catalysis  of  oxidation  reactions  for pharmaceuticals,  plastics,  and  hormones.  However, achieving  high coupling efficiency by the engineering of P450s is still a big challenge.The presence of extra water around the active site is deemed to be related touncoupling.  Herein,  we  engineered  the  access  tunnels  of P450 BM3 from Bacillus megaterium to control water access from bulk solvent  to the active  site.  Nine  residues  located  in  tunnels  were investigated bysite  saturationmutagenesisto reduce  the  water diffusion,therefore,improvingthe  coupling  efficiency.  Finally,  the recombinedvariant N319L/T411V/T436A showed improved coupling efficiency (from 31.2%  to 52.6%). Tunnel  polarity  analysis  and  MD simulation  further  proved  that  reduced  water moleculesaround the active  site  lead  to  higher  coupling  efficiency. Overall,  our  research provides   valuable   insight   on   improved   coupling   efficiency   by controlling water diffusion through tunnel engineering.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 366
TI  - Ecdysteroids as potent enzyme inhibitors and verification of their activity using in vitro and in silico docking studies
JO  - Life
PY  - 2022
SP  - 824
AU  - Mamadalieva, N. Z.
AU  - Hussain, H.
AU  - Mollica, A.
AU  - Zengin, G.
AU  - Mamadalieva, R. Z.
AU  - Elhady, S. S.
AU  - Fadil, S. A.
AU  - Ashour, M. L.
AU  - Youssef, F. S.
AU  - 
VL  - 12
UR  - https://doi.org/10.3390/life12060824
DO  - 10.3390/life12060824
AB  - Ecdysteroids represent arthropods’ steroidal hormones, and they exist in about 5–6% of plant species. In this study, the enzyme inhibitory activity of 20 ecdysteroids was assessed for the first time via determining their inhibition versus acetylcholinesterase, butyrylcholinesterase, tyrosinase, as well as α-amylase enzymes. Furthermore, 20-Hydroxyecdysone-2,3,22-tri-O-acetate (4) showed the highest inhibition of acetylcholinesterase and butyrylcholinesterase with values of 5.56 and 4.76 mg GALAE/g, respectively. All ecdysteroids displayed tyrosinase inhibitory effects, whereas the most potent was viticosterone E (7) with 78.88 mg KAE/g. Most ecdysteroids had similar amylase inhibitory properties; meanwhile, the best α-amylase inhibitory potential was observed with viticosterone E-diacetonide (18) (0.35 mmol ACAE/g). Most of the tested compounds showed tyrosinase inhibitory potential; therefore, they were exposed to molecular docking evaluation using the tyrosinase enzyme. Viticosterone E (7) showed the best ranking score with a docking score of −5.716 Kcal/mol and made three separate H-bonds with Gly281, Asn81, and His85. From ADMET /TOPKAT in silico evaluation, it was obvious that most of the compounds displayed reasonable pharmacodynamic and pharmacokinetic properties; however, their toxicity should be carefully monitored by adjusting their doses while investigating their activity after incorporation into dosage forms. Principal component analysis (PCA) based upon the in vitro and in silico data was carried out to visualize the differences between the tested compounds better. PCA score plot successfully classifies the compounds into four main clusters that, in turn, reflects the similarities and differences among the clustered compounds with respect to their biological, pharmacokinetic, and pharmacodynamic properties that are mainly influenced by the similarity in the chemical structure. Thus, ecdysteroids can act as effective drug entities for alleviating several disorders owing to their enzyme inhibitory potential.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 365
TI  - Emergence of resistance against direct acting antivirals in chronic HCV patients: A real-world study
JO  - Saudi Journal of Biological Sciences
PY  - 2022
SP  - 2613-2619
AU  - Majid, A.
AU  - Khan, S.
AU  - Siraj, S.
AU  - Haleem, S.
AU  - ul Haq, N.
AU  - Ullah, R.
AU  - Ali, E. A.
AU  - Mustafa, A.
AU  - Hussain, H.
AU  - Sohaib, M.
AU  - 
VL  - 29
UR  - https://doi.org/10.1016/j.sjbs.2021.12.044
DO  - 10.1016/j.sjbs.2021.12.044
AB  - Interferon/Ribavirin therapy has been replaced by Direct Acting Antivirals (DAAs) due to emergence of Resistance Associated Variants (RAVs) and decrease Sustain Virologic Response (SVR). Current study investigated treatment response of Sofosbuvir and Ribavirin in chronic HCV patients. Total 256 HCV patients with genotype 1a, 2 and 3a received sofosbuvir/ribavirin according to international standards. HCV RNA presence in serum was used as marker for end treatment response (ETR) and sustain virologic response after 24 weeks of treatment (SVR24) in each case. Response to treatment with SOF + RBV was found statistically significant among different HCV genotypes (GT) as out of 47 HCV GT1 patients 42 (89.36%) resulted into good ETR but 4(9.52%) of these relapsed and 5(10.63%) led into virologic failure. (100%) HCV GT2 patients resulted into SVR24 whereas, out of 204 HCV GT3 patients 194(95.69%) achieved good ETR however, 8(4.12%) of these relapsed and 10(4.90%) resulted in to virologic failure. Efficacy of therapy was found non-significant in treatment naïve and treatment experienced patients as in this study out of 145 treatment naïve patients 139(95.86%) achieved good ETR where 4(2.87%) relapsed while 6(4.13%) led into virologic break through on the other hand among 111 treatment experienced patients 102(91.89%) resulted into good ETR but 8(7.84%) relapsed whereas 9(8.10%) lead into virologic failure. Current study also propose that various liver and spleen complications/liver cirrhosis are related to response of HCV patients to SOF + RBV therapy whereas, variables like old age, gender is not compromising treatment response to DAAs therapy. Various mild side effects encountered by patients during treatment were fatigue, insomnia, headache, nausea, burning body, diarrhea, cough. Overall, this study reported 89.45% efficacy of SOF + RBV regime in chronic HCV Pakistani patients. Current study suggests hunting for possible reasons of resistance so that SOF + RBV therapy may not share the same fortune as previous therapies in near future.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 363
TI  - Flexibility regulation of loops surrounding the tunnel entrance in cytochrome P450 enhanced substrate access substantially
JO  - ACS Catal.
PY  - 2022
SP  - 12800-12808
AU  - Li, Z.
AU  - Meng, S.
AU  - Nie, K.
AU  - Schwaneberg, U.
AU  - Davari, M. D.
AU  - Xu, H.
AU  - Ji, Y.
AU  - Liu, L.
AU  - 
VL  - 12
UR  - https://doi.org/10.1021/acscatal.2c02258
DO  - 10.1021/acscatal.2c02258
AB  - In recent years, the engineering of flexible loops to improve enzyme properties has gained attention in biocatalysis. Herein, we report a loop engineering strategy to improve the stability of the substrate access tunnels, which reveals the molecular mechanism between loops and tunnels. Based on the dynamic tunnel analysis of CYP116B3, five positions (A86, T91, M108, A109, T111) in loops B-B′ and B′-C potentially affecting tunnel frequent occurrence were selected and subjected to simultaneous saturation mutagenesis. The best variant 8G8 (A86T/T91L/M108N/A109M/T111A) for the dealkylation of 7-ethoxycoumarin and the hydroxylation of naphthalene was identified with considerably increased activity (134-fold and 9-fold) through screening. Molecular dynamics simulations showed that the reduced flexibility of loops B-B′ and B′-C was responsible for increasing the stability of the studied tunnel. The redesign of loops B-B′ and B′-C surrounding the tunnel entrance provides loop engineering with a powerful and likely general method to kick on/off the substrate/product transportation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 362
TI  - Does filter-aided sample preparation provide sufficient method linearity for quantitative plant shotgun proteomics?
JO  - Front. Plant Sci.
PY  - 2022
SP  - 874761
AU  - Leonova, T.
AU  - Ihling, C.
AU  - Saoud, M.
AU  - Frolova, N.
AU  - Rennert, R.
AU  - Wessjohann, L. A.
AU  - Frolov, A.
AU  - 
VL  - 13
UR  - https://doi.org/10.3389/fpls.2022.874761
DO  - 10.3389/fpls.2022.874761
AB  - Due to its outstanding throughput and analytical resolution, gel-free LC-based shotgun proteomics represents the gold standard of proteome analysis. Thereby, the efficiency of sample preparation dramatically affects the correctness and reliability of protein quantification. Thus, the steps of protein isolation, solubilization, and proteolysis represent the principal bottleneck of shotgun proteomics. The desired performance of the sample preparation protocols can be achieved by the application of detergents. However, these compounds ultimately compromise reverse-phase chromatographic separation and disrupt electrospray ionization. Filter-aided sample preparation (FASP) represents an elegant approach to overcome these limitations. Although this method is comprehensively validated for cell proteomics, its applicability to plants and compatibility with plant-specific protein isolation protocols remain to be confirmed. Thereby, the most important gap is the absence of the data on the linearity of underlying protein quantification methods for plant matrices. To fill this gap, we address here the potential of FASP in combination with two protein isolation protocols for quantitative analysis of pea (Pisum sativum) seed and Arabidopsis thaliana leaf proteomes by the shotgun approach. For this aim, in comprehensive spiking experiments with bovine serum albumin (BSA), we evaluated the linear dynamic range (LDR) of protein quantification in the presence of plant matrices. Furthermore, we addressed the interference of two different plant matrices in quantitative experiments, accomplished with two alternative sample preparation workflows in comparison to conventional FASP-based digestion of cell lysates, considered here as a reference. The spiking experiments revealed high sensitivities (LODs of up to 4 fmol) for spiked BSA and LDRs of at least 0.6 × 102. Thereby, phenol extraction yielded slightly better recoveries, whereas the detergent-based method showed better linearity. Thus, our results indicate the very good applicability of FASP to quantitative plant proteomics with only limited impact of the protein isolation technique on the method’s overall performance.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 361
TI  - Agar-based polyethylene glycol (PEG) infusion model for pea (Pisum sativum L.) — perspectives of translation to legume crop plants
JO  - Biol. Commun.
PY  - 2022
SP  - 236-244
AU  - Leonova, T.
AU  - Shumilina, J.
AU  - Kim, A.
AU  - Frolova, N.
AU  - Wessjohann, L.
AU  - Bilova, T.
AU  - Frolov, A.
AU  - 
VL  - 67
UR  - https://doi.org/10.21638/spbu03.2022.309
DO  - 10.21638/spbu03.2022.309
AB  - Due to the oncoming climate changes water deficit represents one of the most important abiotic stressors which dramatically affects crop productivity worldwide. Because of their importance as the principal source of food protein, legumes attract a special interest of plant scientists. Moreover, legumes are involved in symbiotic association with rhizobial bacteria, which is morphologically localized to root nodules. These structures are critical for fixation of atmospheric nitrogen and highly sensitive to drought. Therefore, new drought-tolerant legume cultivars need to be developed to meet the growing food demand. However, this requires a comprehensive knowledge of the molecular mechanisms behind the plant stress response. To access these mechanisms, adequate and reliable drought stress models need to be established. The agar-based polyethylene glycol (PEG) infusion model allows a physiologically relevant reduction of soil water potential (Ψw), although it is restricted to seedlings and does not give access to proteomics and metabolomics studies. Earlier, we successfully overcame this limitation and optimized this model for mature Arabidopsis plants. Here we make the next step forward and address its application to one of the major crop legumes — pea. Using a broad panel of physiological and biochemical markers, we comprehensively prove the applicability of this setup to legumes. The patterns of drought-related physiological changes are well-interpretable and generally resemble the stress response of plants grown in soil-based stop-watering models. Thus, the proposed model can be efficiently used in the study of stress-related metabolic adjustment in green parts, roots and root nodules of juvenile and flowering plants.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 359
TI  - Anticancer potential of Xanthohumol and Isoxanthohumol loaded into SBA-15 mesoporous silica particles against B16F10 melanoma cells
JO  - Materials
PY  - 2022
SP  - 5028
AU  - Krajnović, T.
AU  - Pantelić, N. ?.
AU  - Wolf, K.
AU  - Eichhorn, T.
AU  - Maksimović-Ivanić, D.
AU  - Mijatović, S.
AU  - Wessjohann, L. A.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 15
UR  - https://doi.org/10.3390/ma15145028
DO  - 10.3390/ma15145028
AB  - Xanthohumol (XN) and isoxanthohumol (IXN), prenylated flavonoids from Humulus lupulus, have been shown to possess antitumor/cancerprotective, antioxidant, antiinflammatory, and antiangiogenic properties. In this study, mesoporous silica (SBA-15) was loaded with different amounts of xanthohumol and isoxanthohumol and characterized by standard analytical methods. The anticancer potential of XN and IXN loaded into SBA-15 has been evaluated against malignant mouse melanoma B16F10 cells. When these cells were treated with SBA-15 containing xanthohumol, an increase of the activity correlated with a higher immobilization rate of XN was observed. Considering the amount of XN loaded into SBA-15 (calculated from TGA), an improved antitumor potential of XN was observed (IC50 = 10.8 ± 0.4 and 11.8 ± 0.5 µM for SBA-15&#124;XN2 and SBA-15&#124;XN3, respectively; vs. IC50 = 18.5 ± 1.5 µM for free XN). The main mechanism against tumor cells of immobilized XN includes inhibition of proliferation and autophagic cell death. The MC50 values for SBA-15 loaded with isoxanthohumol were over 300 µg/mL in all cases investigated.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 358
TI  - Combinatorial InVitroFlow‐assisted Mutagenesis (CombIMut) yields a 41‐fold improved CelA2 cellulase
JO  - Biotechnology and Bioengineering
PY  - 2022
SP  - 2076–2087
AU  - Körfer, G.
AU  - Besirlioglu, V.
AU  - Davari, M. D.
AU  - Martinez, R.
AU  - Vojcic, L.
AU  - Schwaneberg, U.
AU  - 
VL  - 119
UR  - https://doi.org/10.1002/bit.28110
DO  - 10.1002/bit.28110
AB  - The combination of diversity generation methods and ultrahigh-throughput screening (uHTS) technologies is key to efficiently explore nature\'s sequence space and elucidate structure-function relationships of enzymes. Beneficial substitutions often cluster in a few regions and simultaneous amino acid substitutions at multiple positions (e.g., by OmniChange) will likely lead to further improved enzyme variants. An extensive screening effort is required to identify such variants, as the simultaneous randomization of four codons can easily yield over 105 potential enzyme variants. The combination of flow cytometer-based uHTS with cell-free compartmentalization technology using (w/o/w) double emulsions (InVitroFlow), provides analysis capabilities of up to 107 events per hour, thus enabling efficient screening. InVitroFlow is an elegant solution since diversity loss through a transformation of host cells is omitted and emulsion compartments provide a genotype-phenotype linkage through a fluorescence readout. In this work, a multi-site saturation mutagenesis (mSSM) and an OmniChange library with four simultaneously saturated positions in the active site of CelA2 cellulase were screened using InVitroFlow. Screening of over 36 million events, yielded a significantly improved cellulase variant CelA2-M3 (H288F/H524Q) with an 8-fold increase in specific activity compared to the parent CelA2-H288F (83.9 U/mg) and a 41-fold increased specific activity (674.5 U/mg) compared to wildtype CelA2 (16.6 U/mg) for the substrate 4-MUC (4-methylumbelliferyl-β D-cellobioside).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 357
TI  - Assessing phytoequivalency of four Zingiberaceae spices (galangals, turmeric and ginger) using a biochemometric approach: A case study
JO  - Industrial Crops and Products
PY  - 2022
SP  - 115722
AU  - Khattab, A. R.
AU  - Rasheed, D. M.
AU  - El-Haddad, A. E.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - Farag, M. A.
AU  - 
VL  - 188
UR  - https://doi.org/10.1016/j.indcrop.2022.115722
DO  - 10.1016/j.indcrop.2022.115722
AB  - The Zingiberaceae family (the ginger family) encompasses featured candidates used extensively in perfume, dyes, medicine as well as food industries. This study provides NMR metabolite fingerprinting, quantification and biological evaluation of four major plants viz. lesser and greater galangal, curcuma and ginger. 1H NMR derived metabolite profiles of the four spices were modeled via orthogonal partial least squares discriminate analysis (OPLS-DA). The cytotoxic activity of the four plants against colon and prostate cancer cell lines and in-vitro cyclooxygenase-1 inhibition activity were also evaluated. A correlation between the plants’ bioactivities and their 1H NMR metabolite profiles was established using OPLS and revealed putative metabolites responsible for these bioactivities. The most active cytotoxic plant was greater galangal due to its enrichment in galangal acetate. In contrast, lesser galangal exhibited the strongest anti-inflammatory action being enriched in 5-hydroxy-7-(4ꞌ-hydroxy-3 ꞌ-methoxyphenyl)-1-phenyl-3-heptanone and kaempferide. This study provides insight on the potential medicinal merit of genus Alpinia comparable to the more explored drugs turmeric and ginger within the Zingiberaceae family.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 356
TI  - Physiochemical evaluations, mechanical attenuations and thermal stability of graphene nanosheets and functionalized nanodiamonds loaded pitch derived carbon foam composites
JO  - Diamond and Related Materials
PY  - 2022
SP  - 109077
AU  - Khan, M.
AU  - Tiehu, L.
AU  - Hussain, A.
AU  - Raza, A.
AU  - Zada, A.
AU  - Alei, D.
AU  - Khan, A. R.
AU  - Ali, R.
AU  - Hussain, H.
AU  - Hussain, J.
AU  - Wahab, Z.
AU  - Imran, M.
AU  - 
VL  - 126
UR  - https://doi.org/10.1016/j.diamond.2022.109077
DO  - 10.1016/j.diamond.2022.109077
AB  - This work explains the synergistic effects of graphene nanosheets (GNS) and functionalized nanodiamonds (FNDs) on the pitch derived carbon foam (CF) composite to improve its electrical, mechanical, and thermal properties. Two different types of (1, 2 and 4 wt%) CF/GNS and CF/GNS-FNDs hybrid composites were prepared via pretreatment, foaming, carbonization and graphitization from coal tar pitches. The additive role of GNS and FNDs was studied by varying their amounts in CF matrix. The structure and morphological investigations of the composite reveal that pore size and cellular structure are significantly improved with the addition of additives amount. Moreover, electrical, mechanical and thermal properties of CF/GNS-FNDs hybrid composites are much higher than CF/GNS and pure CFs. Maximum in-plane electrical (20.20 × 103 Sm−1) and thermal (29.95 W m−1 K−1 at 800 °C) conductivities were revealed by 4 wt% CF/GNS-FND hybrid composite. Similarly, optimum values of 19.22 and 46.08 MPa of compressive strength and Young\'s modulus were represented by 2 wt% CF/GNS-FND hybrid composites which effectively suggests the role and importance of FNDs in the CF composites.Graphical abstract
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 355
TI  - Omicron: A new face of
            COVID
            ‐19 pandemic
JO  - Health Science Reports
PY  - 2022
SP  - e526
AU  - Khan, A.
AU  - Bibi, S.
AU  - Kanwal, H.
AU  - Umm‐e‐Kalsoom, .
AU  - Hussain, H.
AU  - 
VL  - 5
UR  - https://doi.org/10.1002/hsr2.526
DO  - 10.1002/hsr2.526
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 354
TI  - Ecological risk assessment and bioaccumulation of trace element, copper, in wheat varieties irrigated with non-conventional water resources in a semi-arid tropics
JO  - Agricultural Water Management
PY  - 2022
SP  - 107711
AU  - Khan, Z. I.
AU  - Hussain, M. I.
AU  - Zafar, A.
AU  - Ahmad, K.
AU  - Ashraf, M. A.
AU  - Ahmed, M.
AU  - ALrashidi, A. A.
AU  - ALHaithloul, H. A. S.
AU  - Alghanem, S. M.
AU  - Khan, M. I.
AU  - Hamid, Y.
AU  - Hussain, H.
AU  - 
VL  - 269
UR  - https://doi.org/10.1016/j.agwat.2022.107711
DO  - 10.1016/j.agwat.2022.107711
AB  - In developing countries, using non-conventional water for irrigation is a traditional and cost-effective tool. However, its long-term use for agriculture and forestry will led to toxic metal bioaccumulation in plants and soil environment. Copper (Cu) is an essential plant nutrient but its excess accumulation can cause significant issues and risks to human health following food crop consumption. The present study was conducted with the aim to assess impact of copper (Cu) in the five wheat varieties (Seher-2006, Faislabad-2008, Watan, Galaxy-2013, Punjab-2011) at 7-ecological sites during the two growing seasons (2017, 2018). The source of irrigation included the ground water, industrial wastewater and sewage water. The Cu concentrations were subsequently determined via ecological environment (water, soils) and below and above ground plant organs (shoots, roots, and wheat grains) and phytostabilization potential assessment using various pollution indices. Results of this study revealed that mean Cu concentration in different wheat varieties and treatments were varied from 1.53 to 1.07–3.22 mg/kg, 0.58 and 1.94 mg/kg, 0.43–2.39 mg/kg, and 0.23–0.78 mg/kg in amended soil, root, shoot, and grains, respectively. Wheat cultivar, Seher-2006 showed highest Cu transfer from shoot to grain following irrigation with ground water while lowest after industrial water irrigation. High content of Cu was obtained in water and toxicity was higher than the maximum permissible limit. In case of grain and soil samples the copper contents were present within the safe limits. The value of all the indices for Cu were found less than 1 except for bioaccumulation factor and translocation factor that were greater than 1 for some samples. Our results revealed that the studied varieties of wheat crop were safe for consumption but the continuous usage of wastewater for irrigation may pose health risks after many years of consumption because some samples showed the high value for bioaccumulation factor and transfer factor. Wheat varieties possess desirable traits that are vital for phytoremediation purposes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 351
TI  - Theobroma cacao L. cultivar CCN 51: a comprehensive review on origin, genetics, sensory properties, production dynamics, and physiological aspects
JO  - PeerJ
PY  - 2022
SP  - e12676
AU  - Jaimez, R. E.
AU  - Barragan, L.
AU  - Fernández-Niño, M.
AU  - Wessjohann, L. A.
AU  - Cedeño-Garcia, G.
AU  - Sotomayor Cantos, I.
AU  - Arteaga, F.
AU  - 
VL  - 10
UR  - https://doi.org/10.7717/peerj.12676
DO  - 10.7717/peerj.12676
AB  - Many decades of improvement in cacao have aided to obtain cultivars with characteristics of tolerance to diseases, adaptability to different edaphoclimatic conditions, and higher yields. In Ecuador, as a result of several breeding programs, the clone CCN 51 was obtained, which gradually expanded through the cacao-production regions of Ecuador, Colombia, Brazil and Peru. Recognized for its high yield and adaptability to different regions and environments, it has become one of the most popular clones for breeding programs and cultivation around the world. This review aims to summarize the current evidence on the origin, genetics, morphological, volatile compounds, and organoleptic characteristics of this clone. Physiological evidence, production dynamics, and floral biology are also included to explain the high yield of CCN 51. Thus, characteristics such as osmotic adjustment, long pollen longevity, and fruit formation are further discussed and associated with high production at the end of the dry period. Finally, the impact of this popular clone on the current and future cacao industry will be discussed highlighting the major challenges for flavor enhancement and its relevance as a platform for the identification of novel genetic markers for cultivar improvement in breeding programs.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 349
TI  - The potential role of dietary plant ingredients against mammary cancer: a comprehensive review
JO  - Crit. Rev. Food Sci. Nutr.
PY  - 2022
SP  - 2580-2605
AU  - Hussain, A.
AU  - Bourguet-Kondracki, M.-L.
AU  - Hussain, F.
AU  - Rauf, A.
AU  - Ibrahim, M.
AU  - Khalid, M.
AU  - Hussain, H.
AU  - Hussain, J.
AU  - Ali, I.
AU  - Khalil, A. A.
AU  - Alhumaydhi, F. A.
AU  - Khan, M.
AU  - Hussain, R.
AU  - Rengasamy, K. R. R.
AU  - 
VL  - 62
UR  - https://doi.org/10.1080/10408398.2020.1855413
DO  - 10.1080/10408398.2020.1855413
AB  - Breast cancer is known as the most devastating cancer in the global 
female community and is considered as one of the severe health care 
burdens in both developed and developing countries. In many cases, 
breast cancer has shown resistance to chemotherapy, radiotherapy and 
hormonal therapy. Keeping in view these limitations, there is an urgent 
need to develop safe, readily available and effective breast anticancer 
treatments. Therefore, the scientists are keen in the extraction of 
plant-based phytochemicals (organosulfur compounds, betalains, 
capsaicinoids, terpenes, terpenoids, polyphenols, and flavonoids) and 
using them as breast anticancer agents. Results of numerous 
epidemiological investigations have revealed the promising role of 
phytochemicals in the prevention and treatment of breast cancer. The 
diverse classes of plant bioactive metabolites regulate different 
metabolic and molecular processes, which can delay the proliferation of 
cancers. These phytochemicals possess chemo-preventive properties as 
they down-regulate the expression of estrogen receptor-α, inhibit the 
proliferation of cancer cells, and cause cell cycle arrest by inducing 
apoptotic conditions in tumor cells. This review article discusses the 
potent role of various plant-based phytochemicals as potential 
therapeutic agents in the treatment or prevention of breast cancer along with the proposed mechanisms of action.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 348
TI  - Quantitative ethnomedicinal study of indigenous knowledge on medicinal plants used by the tribal communities of Central Kurram, Khyber Pakhtunkhwa, Pakistan
JO  - Ethnobot. Res. App.
PY  - 2022
SP  - 1-30
AU  - Hussain, S.
AU  - Hussain, W.
AU  - Nawaz, A.
AU  - Badshah, L.
AU  - Ali, A.
AU  - Ullah, S.
AU  - Ali, M.
AU  - Hussain, H.
AU  - Bussmann, R. W.
AU  - 
VL  - 23
UR  - http://dx.doi.org/10.32859/era.23.5.1-31
DO  - 10.32859/era.23.5.1-31
AB  - Background: The use of plants for different ethnobotanical purposes is a common practice in the remote areas of developing countries, particularly in reference to human and animal healthcare. For this aim, it is important to document ethnomedicinal use of plants for human and livestock healthcare from unexplored regions.
Objective: The current study aimed to document the use of medicinal plants and to assess their conservation status. We hypothesized that Central Kurram, due to its remoteness and maintenance of traditions would show distinct differences in medicinal plant use in comparison to other areas of Pakistan.
Method: The data was collected through semi-structured interviews and was analyzed using various quantitative indices including use value (UV), relative frequency of citation (RFC), use report (UR), fidelity level (FL), informant consensus factor (ICF) and family importance value (FIV). Plant samples were collected identified and then processed as voucher specimens following standard ethnobotanical practice.
Results: One hundred twenty participants including 80 men and 40 women were interviewed. The participants reported a total of 106 plant species, belonging to 96 genera and 50 families. There were two families of pteridophytes (2 species), 2 families of gymnosperm (4 species) and 100 species belonging to 46 families of2 angiosperms. The local population used therapeutic plants to heal 114 different diseases in 19 aliment categories in the study area. A total of 106 species belonging to 50 families were documented as used to treat different types of illness. The UV ranged from 0.01 (Artemisia scoparia and Malva sylvestris) to 0.75 (Conyza canadensis). The RFC varied from 0.025 (Hyoscyamus niger and Senecio crysanthemoides) to 1.992 (Ephedra intermedia). The species with 100% FL were Astragalus stocksii and Artemisia scoparia, while the FCI ranged from 0 to 1 for insecticides and acoustic disorders. The conservation assessment revealed that 49 plant species were vulnerable, followed by rare (34 spp.), infrequent (7 spp.), Dominant (5spp.) And 5 endangered species.
Conclusion: The current study showed that Central Kurram has a significant diversity of medicinal plant, and the use of medicinal plants and plant-based remedies is still common in the area. A total of 106 medicinal plant species, belonging to 50 families were documented for the treatment of 114 disorders. The residents used medicinal plants in treatment of important diseases such as Covid-19, cancer, dysentery, as diuretic, wound healing, and sexual diseases.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 347
TI  - Prof. Ludger Wessjohann: A lifelong career dedicated to a remarkable service in “Natural products sciences”
JO  - Int. J. Mol. Sci.
PY  - 2022
SP  - 5440
AU  - Hussain, H.
AU  - 
VL  - 23
UR  - https://doi.org/10.3390/ijms23105440
DO  - 10.3390/ijms23105440
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 346
TI  - Fruit peels: Food waste as a valuable source of bioactive natural products for drug discovery
JO  - Current Issues in Molecular Biology
PY  - 2022
SP  - 1960-1994
AU  - Hussain, H.
AU  - Mamadalieva, N. Z.
AU  - Hussain, A.
AU  - Hassan, U.
AU  - Rabnawaz, A.
AU  - Ahmed, I.
AU  - Green, I. R.
AU  - 
VL  - 44
UR  - https://doi.org/10.3390/cimb44050134
DO  - 10.3390/cimb44050134
AB  - Fruits along with vegetables are crucial for a balanced diet. These not only have delicious flavors but are also reported to decrease the risk of contracting various chronic diseases. Fruit by-products are produced in huge quantity during industrial processing and constitute a serious issue because they may pose a harmful risk to the environment. The proposal of employing fruit by-products, particularly fruit peels, has gradually attained popularity because scientists found that in many instances peels displayed better biological and pharmacological applications than other sections of the fruit. The aim of this review is to highlight the importance of fruit peel extracts and natural products obtained in food industries along with their other potential biological applications.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 345
TI  - Frankincense diterpenes as a bio-source for drug discovery
JO  - Expert Opinion on Drug Discovery
PY  - 2022
SP  - 513-529
AU  - Hussain, H.
AU  - Rashan, L.
AU  - Hassan, U.
AU  - Abbas, M.
AU  - Hakkim, F. L.
AU  - Green, I. R.
AU  - 
VL  - 17
UR  - https://doi.org/10.1080/17460441.2022.2044782
DO  - 10.1080/17460441.2022.2044782
AB  - Introduction 
Frankincense (Boswellia sp.) gum resins have been employed as an incense in cultural and religious ceremonies for many years. Frankincense resin has over the years been employed to treat depression, inflammation, and cancer in traditional medicines.

Areas coveredThis inclusive review focuses on the significance of frankincense diterpenoids, and in particular, incensole derivatives for establishment future treatments of depression, neurological disorders, and cancer. The authors survey the available literature and furnish an overview of future perspectives of these intriguing molecules.

Expert opinion
Numerous diterpenoids including cembrane, prenylaromadendrane, and the verticillane-type have been isolated from various Boswellia resins. Cembrane-type diterpenoids occupy a crucial position in pharmaceutical chemistry and related industries because of their intriguing biological and encouraging pharmacological potentials. Several cembranes have been reported to possess anti-Alzheimer, anti-inflammatory, hepatoprotective, and antimalarial effects along with a good possibility to treat anxiety and depression. Although some slight drawbacks of these compounds have been noted, including the selectivity of these diterpenoids, there is a great need to address these in future research endeavors. Moreover, it is vitally important for medicinal chemists to prepare libraries of incensole-heterocyclic analogs as well as hybrid compounds between incensole or its acetate and anti-depressant or anti-inflammatory drugs.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 344
TI  - Editorial to special issue “Theme issue honoring Prof. Dr. Ludger Wessjohann’s 60th birthday: Natural products in modern drug discovery”
JO  - Int. J. Mol. Sci.
PY  - 2022
SP  - 5835
AU  - Hussain, H.
AU  - 
VL  - 23
UR  - https://doi.org/10.3390/ijms23105835
DO  - 10.3390/ijms23105835
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 343
TI  - Quantitative NMR for the structural analysis of novel bivalent glycoconjugates as vaccine candidates
JO  - J. Pharm. Biomed. Anal.
PY  - 2022
SP  - 114721
AU  - Humpierre, A. R.
AU  - Zanuy, A.
AU  - Saenz, M.
AU  - Vasco, A. V.
AU  - Méndez, Y.
AU  - Westermann, B.
AU  - Cardoso, F.
AU  - Quintero, L.
AU  - Santana, D.
AU  - Verez, V.
AU  - Valdés, Y.
AU  - Rivera, D. G.
AU  - Garrido, R.
AU  - 
VL  - 214
UR  - https://doi.org/10.1016/j.jpba.2022.114721
DO  - 10.1016/j.jpba.2022.114721
AB  - Novel unimolecular bivalent glycoconjugates were assembled combining several functionalized capsular polysaccharides of Streptococcus pneumoniae and Neisseria meningitidis to a carrier protein by using an effective strategy based on the Ugi 4-component reaction. The development of multivalent glycoconjugates opens new opportunities in the field of vaccine design, but their high structural complexity involves new analytical challenges. Nuclear Magnetic Resonance has found wide applications in the characterization and impurity profiling of carbohydrate-based vaccines. Eight bivalent conjugates were studied by quantitative NMR analyzing the structural identity, the content of each capsular polysaccharide, the ratios between polysaccharides, the polysaccharide to protein ratios and undesirable contaminants. The qNMR technique involves experiments with several modified parameters for obtaining spectra with quantifiable signals. In addition, the achieved NMR results were combined with the results of colorimetric assay and Size Exclusion HPLC for assessing the protein content and free protein percentage, respectively. The application of quantitative NMR showed to be efficient to clear up the new structural complexities while allowing the quantitative assessment of the components.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 340
TI  - Lipidomic profiling of bioactive lipids during spontaneous fermentations of fine-flavor cocoa
JO  - Food Chem.
PY  - 2022
SP  - 133845
AU  - Herrera-Rocha, F.
AU  - Cala, M. P.
AU  - León-Inga, A. M.
AU  - Aguirre Mejía, J. L.
AU  - Rodríguez-López, C. M.
AU  - Florez, S. L.
AU  - Chica, M. J.
AU  - Olarte, H. H.
AU  - Duitama, J.
AU  - González Barrios, A. F.
AU  - Fernández-Niño, M.
AU  - 
VL  - 397
UR  - https://doi.org/10.1016/j.foodchem.2022.133845
DO  - 10.1016/j.foodchem.2022.133845
AB  - The impact of cocoa lipid content on chocolate quality has been extensively described. Nevertheless, few studies have elucidated the cocoa lipid composition and their bioactive properties, focusing only on specific lipids. In the present study the lipidome of fine-flavor cocoa fermentation was analyzed using LC-MS-QTOF and a Machine Learning model to assess potential bioactivity was developed. Our results revealed that the cocoa lipidome, comprised mainly of fatty acyls and glycerophospholipids, remains stable during fine-flavor cocoa fermentations. Also, several Machine Learning algorithms were trained to explore potential biological activity among the identified lipids. We found that K-Nearest Neighbors had the best performance. This model was used to classify the identified lipids as bioactive or non-bioactive, nominating 28 molecules as potential bioactive lipids. None of these compounds have been previously reported as bioactive. Our work is the first untargeted lipidomic study and systematic effort to investigate potential bioactivity in fine-flavor cocoa lipids.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 339
TI  - Authentication of saffron spice accessions from its common substitutes via a multiplex approach of UV/VIS fingerprints and UPLC/MS using molecular networking and chemometrics
JO  - Food Chem.
PY  - 2022
SP  - 130739
AU  - Hegazi, N. M.
AU  - Khattab, A. R.
AU  - Frolov, A.
AU  - Wessjohann, L. A.
AU  - Farag, M. A.
AU  - 
VL  - 367
UR  - https://doi.org/10.1016/j.foodchem.2021.130739
DO  - 10.1016/j.foodchem.2021.130739
AB  - Saffron is a spice revered for its unique flavor and health attributes 
often subjected to fraudulence. In this study, molecular networking as a
 visualization tool for UPLC/MS dataset of saffron and its common 
substitutes i.e. safflower and calendula (n = 21) was employed for determining genuineness of saffron and detecting its common substitutes i.e. safflower and calendula. Saffron was abundant in flavonol-O-glycosides
 and crocetin esters versus richness of flavanones/chalcones glycosides 
in safflower and cinnamates/terpenes in calendula. OPLS-DA identified 
differences in UPLC/MS profiles of different saffron accessions where 
oxo-hydroxy-undecenoic acid-O-hexoside was posed as saffron 
authentication marker and aided in discrimination between Spanish 
saffron of high quality from its inferior grade i.e. Iranian saffron along with crocetin di-O-gentiobiosyl ester and kaempferol-O-sophoroside. Kaempferol-O-neohesperidoside and N,N,N,-p-coumaroyl spermidine were characteristic safflower metabolites, whereas, calendulaglycoside C and di-O-caffeoyl
 quinic acid were unique to calendula. UV/VIS fingerprint spectral 
regions of picrocrocin (230–260 nm) and crocin derivatives (400–470 nm) 
were posed as being discriminatory of saffron authenticity and 
suggestive it can replace UPLC/MS in saffrom quality determination.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 337
TI  - Plant-derived smoke ameliorates salt stress in wheat by enhancing expressions of stress-responsive genes and antioxidant enzymatic activity
JO  - Agronomy
PY  - 2022
SP  - 28
AU  - Hayat, N.
AU  - Afroz, N.
AU  - Rehman, S.
AU  - Bukhari, S. H.
AU  - Iqbal, K.
AU  - Khatoon, A.
AU  - Taimur, N.
AU  - Sakhi, S.
AU  - Ahmad, N.
AU  - Ullah, R.
AU  - Ali, E. A.
AU  - Bari, A.
AU  - Hussain, H.
AU  - Nawaz, G.
AU  - 
VL  - 12
UR  - https://doi.org/10.3390/agronomy12010028
DO  - 10.3390/agronomy12010028
AB  - Abiotic stresses are the biggest threat to the increasing population worldwide. Salt stress is one of the most significant abiotic stresses, affecting 20% of the crop production around the world. Plant-derived smoke (PDS) has been reported as a biologically active plant product in stimulating seed germination, seedling growth and physiological characteristics of crops under abiotic stress conditions. Nevertheless, studies showing how PDS alleviates salt stress are largely unknown. Here, we report the molecular mechanism of how PDS could alleviate salt stress in wheat. Initially, PDS at 2000 ppm enhanced seed germination, root/shoot length and seedling fresh weight. However, PDS at 1000 and 500 ppm did not show any significant effect. Salt stress at 150 and 200 mM significantly reduced seed germination rate, root/shoot length and fresh weight of the wheat seedlings. Interestingly, PDS supplementation at 2000 ppm concentration was sufficient to restore seed germination under salt stress condition. Moreover, PDS improved root/shoot length and seedling biomass under 150 and 200 mM salt stress, suggesting that PDS is a potent plant product, capable of abiotic stress alleviation in crops. In comparison to the control, PDS-treated seedlings displayed increased activity of major antioxidative enzymes such as superoxide dismutase, peroxidase and ascorbate peroxidase under salt stress, resulting in reduced levels of hydrogen peroxide and lipid peroxidase, showing that PDS can possibly help in salt stress amelioration by regulating redox homeostasis. Importantly, salt stress altered the expression of germination marker genes, such as TaSAM, TaPHY, TaBGU (germination positive effectors), TaLEA and TaGARS34 (germination negative effectors), suggesting the potential role of PDS in the germination pathway under salt stress. Further, PDS modulated the transcript levels of several salt stress stress-responsive genes, including TaSOS4, TaBADH and TaHKT2. In conclusion, this study provides a molecular and physiological basis for elucidating the mechanism of how PDS functions in stress induction in wheat, as well as demonstrates the importance of PDS in agricultural practices, laying the groundwork for future research into the role of PDS in the amelioration of abiotic stresses in various plants.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 336
TI  - Bacterial metalo-aminopeptidases as targets in human infectious diseases
JO  - Current Drug Targets
PY  - 2022
SP  - 1155-1190
AU  - González-Bacerio, J.
AU  - Varela, A. C.
AU  - Aguado, M. E.
AU  - Izquierdo, M.
AU  - Méndez, Y.
AU  - del Rivero, M. A.
AU  - Rivera, D. G.
AU  - 
VL  - 23
UR  - https://www.eurekaselect.com/article/121597
DO  - 10.2174/1389450123666220316085859
AB  - Background: Human infectious diseases caused by bacteria are a worldwide health problem due to the increased resistance of these microorganisms to conventional antibiotics. For this reason, the identification of novel molecular targets and the discovery of new antibacterial compounds is urgently required. Metalo-aminopeptidases are promising targets in bacterial infections. They participate in crucial processes for bacterial growth and pathogenesis, such as protein and peptide degradation to supply amino acids, protein processing, access to host tissues, cysteine supply for redox control, transcriptional regulation, site-specific DNA recombination, and hydrogen sulfide production. Although several of these enzymes are not essential, they are required for virulence and maximal growth in conditions of nutrient limitation and high temperatures.Objective: In this review, we describe the structural, functional and kinetic properties of some examples of bacterial metalo-aminopeptidases, in the context of their use as antibacterial targets. In addition, we present some inhibitors reported for these enzymes.Conclusion: It is necessary a meticulous work to validate these peptidases as good/bad targets and to identify inhibitors with a potential therapeutic use.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 335
TI  - Chemometric analysis based on GC-MS chemical profiles of three Stachys Species from Uzbekistan and their biological activity
JO  - Plants
PY  - 2022
SP  - 1215
AU  - Gad, H. A.
AU  - Mukhammadiev, E. A.
AU  - Zengin, G.
AU  - Musayeib, N. M. A.
AU  - Hussain, H.
AU  - Bin Ware, I.
AU  - Ashour, M. L.
AU  - Mamadalieva, N. Z.
AU  - 
VL  - 11
UR  - https://doi.org/10.3390/plants11091215
DO  - 10.3390/plants11091215
AB  - The chemical composition of the essential oils (EOs) of Stachys byzantina, S. hissarica and S. betoniciflora growing in Uzbekistan were determined, and their antioxidant and enzyme inhibitory activity were assessed. A gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of 143 metabolites accounting for 70.34, 76.78 and 88.63% of the total identified components of S. byzantina, S. hissarica and S. betoniciflora, respectively. Octadecanal (9.37%) was the most predominant in S. betoniciflora. However, n-butyl octadecenoate (4.92%) was the major volatile in S. byzantina. Benzaldehyde (5.01%) was present at a higher percentage in S. hissarica. A chemometric analysis revealed the ability of volatile profiling to discriminate between the studied Stachys species. The principal component analysis plot displayed a clear diversity of Stachys species where the octadecanal and benzaldehyde were the main discriminating markers. The antioxidant activity was evaluated in vitro using 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2-azino bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing power (FRAP), chelating and phosphomolybdenum (PBD). Moreover, the ability of the essential oils to inhibit both acetyl/butyrylcholinesterases (AChE and BChE), α-amylase, α-glucosidase and tyrosinase was assessed. The volatiles from S. hissarica exhibited the highest activity in both the ABTS (226.48 ± 1.75 mg Trolox equivalent (TE)/g oil) and FRAP (109.55 ± 3.24 mg TE/g oil) assays. However, S. betoniciflora displayed the strongest activity in the other assays (174.94 ± 0.20 mg TE/g oil for CUPRAC, 60.11 ± 0.36 mg EDTA equivalent (EDTAE)/g oil for chelating and 28.24 ± 1.00 (mmol TE/g oil) for PBD. Regarding the enzyme inhibitory activity, S. byzantina demonstrated the strongest AChE (5.64 ± 0.04 mg galantamine equivalent (GALAE)/g oil) and tyrosinase inhibitory (101.07 ± 0.60 mg kojic acid equivalent (KAE)/g) activity. The highest activity for BChE (11.18 ± 0.19 mg GALAE/g oil), amylase inhibition (0.76 ± 0.02 mmol acarbose equivalent (ACAE)/g oil) and glucosidase inhibition (24.11 ± 0.06 mmol ACAE/g oil) was observed in S. betoniciflora. These results showed that EOs of Stachys species could be used as antioxidant, hypoglycemic and skincare agents.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 334
TI  - Identification and characterization of natural and semisynthetic quinones as Aurora kinase inhibitors
JO  - J. Nat. Prod.
PY  - 2022
SP  - 1503-1513
AU  - Furqan, M.
AU  - Fayyaz, A.
AU  - Firdous, F.
AU  - Raza, H.
AU  - Bilal, A.
AU  - Saleem, R. S. Z.
AU  - Shahzad-ul-Hussan, S.
AU  - Wang, D.
AU  - Youssef, F. S.
AU  - Al Musayeib, N. M.
AU  - Ashour, M. L.
AU  - Hussain, H.
AU  - Faisal, A.
AU  - 
VL  - 85
UR  - https://doi.org/10.1021/acs.jnatprod.1c01222
DO  - 10.1021/acs.jnatprod.1c01222
AB  - Aurora kinases (Aurora A, B, and C) are a family of serine/threonine kinases that play critical roles during mitotic initiation and progression. Aurora A and B kinases are ubiquitously expressed, and their overexpression and/or amplification in many cancers have been associated with poor prognosis. Several inhibitors that target Aurora kinases A, B, or both have been developed during the past decade with efficacy in different in vitro and in vivo models for a variety of cancers. Recent studies have also identified Aurora A as a synthetic lethal target for different tumor suppressors, including RB1, SMARCA4, and ARID1A, which signifies the need for Aurora-A-selective inhibitors. Here, we report the screening of a small library of quinones (nine naphthoquinones, one orthoquinone, and one anthraquinone) in a biochemical assay for Aurora A kinase that resulted in the identification of several quinones as inhibitors. IC50 determination against Aurora A and B kinases revealed the inhibition of both kinases with selectivity toward Aurora A. Two of the compounds, natural quinone naphthazarin (1) and a pseudo anthraquinone, 2-(chloromethyl)quinizarin (11), potently inhibited the proliferation of various cancer cell lines with IC50 values ranging from 0.16 ± 0.15 to 1.7 ± 0.06 and 0.15 ± 0.04 to 6.3 ± 1.8 μM, respectively. Treatment of cancer cells with these compounds for 24 h resulted in abrogated mitosis and apoptotic cell death. Direct binding of both the compounds with Aurora A kinase was also confirmed through STD NMR analysis. Docking studies predicted the binding of both compounds to the ATP binding pocket of Aurora A kinase. We have, therefore, identified quinones as Aurora kinase inhibitors that can serve as a lead for future drug discovery.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 333
TI  - Involvement of
            CYP347W1
            in neurotoxin 3‐nitropropionic acid based chemical defense in mustard leaf beetle
            Phaedon cochleariae
JO  - Insect Sci.
PY  - 2022
SP  - 453–466
AU  - Fu, N.
AU  - Becker, T.
AU  - Brandt, W.
AU  - Kunert, M.
AU  - Burse, A.
AU  - Boland, W.
AU  - 
VL  - 29
UR  - https://doi.org/10.1111/1744-7917.12944
DO  - 10.1111/1744-7917.12944
AB  - Chrysomelina beetles store 3-nitropropionic acid in form of a pre-toxin,
 isoxazolin-5-one glucoside conjugated ester, to protect themselves 
against predators. Here we identified a cytochrome P450 monooxygenase, CYP347W1, to be involved in the production of the 3-nitropropionic acid moiety of the isoxazolin-5-one glucoside ester. Knocking down CYP347W1
 led to a significant depletion in the concentration of the 
isoxazolin-5-one glucoside ester and an increase in the concentration of
 the isoxazolin-5-one glucoside in the larval hemolymph. Enzyme assays 
with the heterologously expressed CYP347W1 showed free β-alanine was not the direct substrate. Homology modeling indicated that β-alanine-CoA ester can fit into CYP347W1’s active site. Furthermore, we proved that Phaedon cochleariae eggs are not able to de novo
 synthesize 3-NPA, although both isoxazolin-5-one glucoside and its 
3-NPA conjugated ester are present in the eggs. These results provide 
direct evidence for the involvement of CYP347W1 in the biosynthesis of a P. cochleariae chemical defense compound.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 332
TI  - Metabolomics-based approach for coffee beverage improvement in the context of processing, brewing methods, and quality attributes
JO  - Foods
PY  - 2022
SP  - 864
AU  - Farag, M. A.
AU  - Zayed, A.
AU  - Sallam, I. E.
AU  - Abdelwareth, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 11
UR  - https://doi.org/ 10.3390/foods11060864
DO  - 10.3390/foods11060864
AB  - Coffee is a worldwide beverage of increasing consumption, owing to its unique flavor and several health benefits. Metabolites of coffee are numerous and could be classified on various bases, of which some are endogenous to coffee seeds, i.e., alkaloids, diterpenes, sugars, and amino acids, while others are generated during coffee processing, for example during roasting and brewing, such as furans, pyrazines, and melanoidins. As a beverage, it provides various distinct flavors, i.e., sourness, bitterness, and an astringent taste attributed to the presence of carboxylic acids, alkaloids, and chlorogenic acids. To resolve such a complex chemical makeup and to relate chemical composition to coffee effects, large-scale metabolomics technologies are being increasingly reported in the literature for proof of coffee quality and efficacy. This review summarizes the applications of various mass spectrometry (MS)- and nuclear magnetic resonance (NMR)-based metabolomics technologies in determining the impact of coffee breeding, origin, roasting, and brewing on coffee chemical composition, and considers this in relation to quality control (QC) determination, for example, by classifying defected and non-defected seeds or detecting the adulteration of raw materials. Resolving the coffee metabolome can aid future attempts to yield coffee seeds of desirable traits and best flavor types.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 331
TI  - A comparative metabolomics approach for egyptian mango fruits classification based on UV and UPLC/MS and in relation to its antioxidant effect
JO  - Foods
PY  - 2022
SP  - 2127
AU  - Farag, M. A.
AU  - Abdelwareth, A.
AU  - Zayed, A.
AU  - Eissa, T. F.
AU  - Dokalahy, E.
AU  - Frolov, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 11
UR  - https://doi.org/10.3390/foods11142127
DO  - 10.3390/foods11142127
AB  - Mango (Mangifera indica L.) is a tropical climacteric fruit that encompasses a myriad of metabolites mediating for its nutritive value, unique taste, flavor, and medicinal uses. Egypt is among the top mango producers worldwide, albeit little characterization has been made toward its fruits’ chemical composition. This study aims to assess metabolites difference via comparative profiling and fingerprinting of Egyptian mango in context to its cultivar (cv.) type and/or growth province. To achieve such goal, hyphenated chromatographic techniques (UPLC/MS) and UV spectroscopy were employed and coupled to multivariate data analysis for Egyptian mango fruits’ classification for the first time. UPLC/MS led to the detection of a total of 47 peaks identified based on their elution times and MS data, belonging to tannins as gallic acid esters, flavonoids, xanthones, phenolic acids and oxylipids. UV/Vis spectra of mango fruits showed similar absorption patterns mostly attributed to the phenolic metabolites, i.e., gallic acid derivatives and phenolic acids showing λmax at ca. 240 and 270 nm. Modeling of both UPLC/MS and UV data sets revealed that cv. effect predominated over geographical origin in fruits segregation. Awees (AS) cv. showed the richest phenolic content and in agreement for its recognition as a premium cv. of mango in Egypt. Results of total phenolic content (TPC) assay revealed that AS was the richest in TPC at 179.1 mg GAE/g extract, while Langara from Ismailia (LI) showed the strongest antioxidant effect at 0.41 mg TE/g extract. Partial least square modeling of UV fingerprint with antioxidant action annotated gallates as potential contributor to antioxidant effect though without identification of exact moieties based on UPLC/MS. The study is considered the first-time investigation of Egyptian mango to aid unravel phytoconstituents responsible for fruits benefits using a metabolomics approach.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 329
TI  - How does LC/MS compare to UV in coffee authentication and determination of antioxidant effects? Brazilian and Middle Eastern coffee as case studies
JO  - Antioxidants
PY  - 2022
SP  - 131
AU  - El-Hawary, E. A.
AU  - Zayed, A.
AU  - Laub, A.
AU  - Modolo, L. V.
AU  - Wessjohann, L.
AU  - Farag, M. A.
AU  - 
VL  - 11
UR  - https://doi.org/10.3390/antiox11010131
DO  - 10.3390/antiox11010131
AB  - Coffee is a popular beverage owing to its unique flavor and diverse health benefits. The current study aimed at investigating the antioxidant activity, in relation to the phytochemical composition, of authenticated Brazilian green and roasted Coffea arabica and C. robusta, along with 15 commercial specimens collected from the Middle East. Ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-ESI–HRMS) and UV spectrometry were employed for profiling and fingerprinting, respectively. With the aid of global natural product social molecular networking (GNPS), a total of 88 peaks were annotated as belonging to different chemical classes, of which 11 metabolites are reported for the first time in coffee seeds. Moreover, chemometric tools showed comparable results between both platforms, with more advantages for UV in the annotation of roasting products, suggesting that UV can serve as a discriminative tool. Additionally, antioxidant assays coupled with the UHPLC-ESI–HRMS dataset using partial least-squares discriminant analysis (PLS-DA) demonstrated that caffeoylquinic acid and caffeine were potential antioxidant markers in unroasted coffee versus dicaffeoyl quinolactone and melanoidins in roasted coffee. The study presents a multiplex metabolomics approach to the quality control of coffee, one of the most consumed beverages.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 328
TI  - Critical assessment of structure-based approaches to improve protein resistance in aqueous ionic liquids by enzyme-wide saturation mutagenesis
JO  - Comp Struct Biotechnol J
PY  - 2022
SP  - 399-409
AU  - El Harrar, T.
AU  - Davari, M. D.
AU  - Jaeger, K.-E.
AU  - Schwaneberg, U.
AU  - Gohlke, H.
AU  - 
VL  - 20
UR  - https://doi.org/10.1016/j.csbj.2021.12.018
DO  - 10.1016/j.csbj.2021.12.018
AB  - Ionic liquids (IL) and aqueous ionic liquids (aIL) are attractive (co-)solvents for green industrial processes involving biocatalysts, but often reduce enzyme activity. Experimental and computational methods are applied to predict favorable substitution sites and, most often, subsequent site-directed surface charge modifications are introduced to enhance enzyme resistance towards aIL. However, almost no studies evaluate the prediction precision with random mutagenesis or the application of simple data-driven filtering processes. Here, we systematically and rigorously evaluated the performance of 22 previously described structure-based approaches to increase enzyme resistance to aIL based on an experimental complete site-saturation mutagenesis library of Bacillus subtilis Lipase A (BsLipA) screened against four aIL. We show that, surprisingly, most of the approaches yield low gain-in-precision (GiP) values, particularly for predicting relevant positions: 14 approaches perform worse than random mutagenesis. Encouragingly, exploiting experimental information on the thermostability of BsLipA or structural weak spots of BsLipA predicted by rigidity theory yields GiP = 3.03 and 2.39 for relevant variants and GiP = 1.61 and 1.41 for relevant positions. Combining five simple-to-compute physicochemical and evolutionary properties substantially increases the precision of predicting relevant variants and positions, yielding GiP = 3.35 and 1.29. Finally, combining these properties with predictions of structural weak spots identified by rigidity theory additionally improves GiP for relevant variants up to 4-fold to  ∼10 and sustains or increases GiP for relevant positions, resulting in a prediction precision of ∼ 90% compared to ∼ 9% in random mutagenesis. This combination should be applicable to other enzyme systems for guiding protein engineering approaches towards improved aIL resistance.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 413
TI  - Characterization of silver nanoparticles synthesized by leaves of Lonicera japonica thunb
JO  - International Journal of Nanomedicine
PY  - 2022
SP  - 1647-1657
AU  - Zhang, Y.
AU  - Cui, L.
AU  - Lu, Y.
AU  - He, J.
AU  - Hussain, H.
AU  - Xie, L.
AU  - Sun, X.
AU  - Meng, Z.
AU  - Cao, G.
AU  - Qin, D.
AU  - Wang, D.
AU  - 
VL  - 17
UR  - https://doi.org/10.2147/IJN.S356919
DO  - 10.2147/ijn.s356919
AB  - Background: The leaves of L. japonica (LLJ) are widely used as medicine in China. It is rich in caffeoylquinic acids, flavonoids and iridoid glycosides and has strong reducing capacities. Therefore, it can be used as a green material to synthesize silver nanoparticles.Methods: LLJ was used as a reducing agent to produce the LLJ-mediated silver nanoparticles (LLJ-AgNPs). The structure and physicochemical properties of LLJ-AgNPs were characterized by ultraviolet spectroscopy (UV-Vis), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and x-ray powder diffraction (XRD). Antioxidant activity of LLJ-AgNPs was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging. Antibacterial activity was determined by 96 well plates (AGAR) gradient dilution, while the anticancer potential was determined by MTT assay.Results: The results showed LLJ-AgNPs had a spherical structure with the maximum UV-Vis absorption at 400 nm. In addition, LLJAgNPs exhibited excellent antioxidant properties, where the free radical scavenging rate of LLJ-AgNPs was increased from 39% to 92% at concentrations from 0.25 to 1.0 mg/mL. Moreover, LLJ-AgNPs displayed excellent antibacterial properties against E. coli and Salmonella at room temperature, with minimum inhibitory values of 10−6 and 10−5 g/L, respectively. In addition, the synthetic LLJAgNPs exhibited a better inhibition effect in the proliferation of cancer cells (HepG2, MDA-MB −231, and Hela cells).Conclusion: The present study provides a green approach to synthesize LLJ-AgNPs. All those findings illustrated that the produced LLJ-AgNPs can be used as an economical and efficient functional material for further applications in food and pharmaceutical fields.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 410
TI  - Dissecting coffee seeds metabolome in context of genotype, roasting degree, and blending in the Middle East using NMR and GC/MS techniques
JO  - Food Chem.
PY  - 2022
SP  - 131452
AU  - Zayed, A.
AU  - Abdelwareth, A.
AU  - Mohamed, T. A.
AU  - Fahmy, H. A.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - Farag, M. A.
AU  - 
VL  - 373
UR  - https://doi.org/10.1016/j.foodchem.2021.131452
DO  - 10.1016/j.foodchem.2021.131452
AB  - With a favored taste and various bioactivities, coffee has been consumed
 as a daily beverage worldwide. The current study presented a 
multi-faceted comparative metabolomics approach dissecting commercially 
available coffee products in the Middle East region for quality 
assessment and functional food purposes using NMR and GC/MS platforms. 
NMR metabolites fingerprinting led to identification of 18 metabolites 
and quantification (qNMR) of six prominent markers for standardization 
purposes. An increase of β-ethanolamine (MEA) reported for the 
first time, 5-(hydroxymethyl) furfural (5-HMF), concurrent with a 
reduction in chlorogenic acid, kahweol, and sucrose levels post roasting
 as revealed using multivariate data analyses (MVA). The diterpenes 
kahweol and cafestol were identified in green and roasted Coffea arabica, while 16-O-methyl cafestol in roasted C. robusta.
 Moreover, GC/MS identified a total of 143 metabolites belonging to 15 
different chemical classes, with fructose found enriched in green C. robusta versus fatty acids abundance, i.e., palmitic and stearic acids in C. arabica confirming NMR results. These potential results aided to identify novel quality control attributes, i.e., ethanolamine, for coffee in the Middle East region and have yet to be confirmed in other coffee specimens.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 409
TI  - Synthesis of methylene-bridged trifluoromethyl azoles using 5-(1,2,3-Triazol-1-yl)enones
JO  - Synthesis
PY  - 2022
SP  - 439-450
AU  - Zanatta, N.
AU  - Mittersteiner, M.
AU  - Aquino, E. C.
AU  - Budragchaa, T.
AU  - Wessjohann, L. A.
AU  - Bonacorso, H. G.
AU  - Martins, M. A. P.
AU  - 
VL  - 54
UR  - https://doi.org/10.1055/s-0040-1719837
DO  - 10.1055/s-0040-1719837
AB  - A protocol for synthesizing triazole-containing pyrazolines and pyrazoles selectively using trifluoromethylated 5-(1,2,3-triazol-1-yl)enones as starting materials, is reported. The selectivity of the reaction was controlled by the nature of the hydrazine or derivative used: free hydrazines furnished the 1,5-regiosiomer exclusively in yields up to 98%, whereas protected hydrazines provided the 1,3-regioisomer in yields up to 77%. To demonstrate the synthetic versatility of the triazole-based enone, reactions with other unsymmetrical dinucleophiles (hydroxylamine hydrochloride and S-methyl isothiourea sulfates) allowed the selective preparation of triazole-containing isoxazoline and pyrimidine rings.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 407
TI  - Learning epistasis and residue coevolution patterns: Current trends and future perspectives for advancing enzyme engineering
JO  - ACS Catal.
PY  - 2022
SP  - 14243-14263
AU  - Wittmund, M.
AU  - Cadet, F.
AU  - Davari, M. D.
AU  - 
VL  - 12
UR  - https://doi.org/10.1021/acscatal.2c01426
DO  - 10.1021/acscatal.2c01426
AB  - Engineering proteins and enzymes with the desired
functionality has broad applications in molecular biology,
biotechnology, biomedical sciences, health, and medicine. The
vastness of protein sequence space and all the possible proteins it
represents can pose a considerable barrier for enzyme engineering
campaigns through directed evolution and rational design. The
nonlinear effects of coevolution between amino acids in protein
sequences complicate this further. Data-driven models increasingly
provide scientists with the computational tools to navigate through
the largely undiscovered forest of protein variants and catch a
glimpse of the rules and effects underlying the topology of sequence
space. In this review, we outline a complete theoretical journey
through the processes of protein engineering methods such as
directed evolution and rational design and reflect on these strategies and data-driven hybrid strategies in the context of sequence
space. We discuss crucial phenomena of residue coevolution, such as epistasis, and review the history of models created over the past
decade, aiming to infer rules of protein evolution from data and use this knowledge to improve the prediction of the structure−
function relationship of proteins. Data-driven models based on deep learning algorithms are among the most promising methods
that can account for the nonlinear phenomena of sequence space to some degree. We also critically discuss the available models to
predict evolutionary coupling and epistatic effects (classical and deep learning) in terms of their capabilities and limitations. Finally,
we present our perspective on possible future directions for developing data-driven approaches and provide key orientation points
and necessities for the future of the fast-evolving field of enzyme engineering.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 405
TI  - Heterocyclic and alkyne terpenoids by terpene synthase‐mediated biotransformation of non‐natural prenyl diphosphates: Access to new fragrances and probes
JO  - ChemBioChem
PY  - 2022
SP  - e202200211
AU  - Weigel, B.
AU  - Ludwig, J.
AU  - Weber, R. A.
AU  - Ludwig, S.
AU  - Lennicke, C.
AU  - Schrank, P.
AU  - Davari, M. D.
AU  - Nagia, M.
AU  - Wessjohann, L. A.
AU  - 
VL  - 23
UR  - https://doi.org/10.1002/cbic.202200211
DO  - 10.1002/cbic.202200211
AB  - Terpene synthase-mediated biotransformation of eleven synthetic sulfur- or oxygen-containing non-natural prenyl diphosphates resulted in the formation of five novel terpenoids and analogues. Uniquely, they trap intermediate steps and form heterocycles or compounds with alkyne side chains. Computational modelling differentiates convertible from inconvertible substrates and thereby provides an understanding of the detailed molecular mechanism of terpene cyclases. Two terpene cyclases were used as biocatalytic tool, namely, limonene synthase from Cannabis sativa (CLS) and 5-epi-aristolochene synthase (TEAS) from Nicotiana tabacum. They showed significant substrate flexibility towards non-natural prenyl diphosphates to form novel terpenoids, including core oxa- and thia-heterocycles and alkyne-modified terpenoids. We elucidated the structures of five novel monoterpene-analogues and a known sesquiterpene-analogue. These results reflected the terpene synthases′ ability and promiscuity to broaden the pool of terpenoids with structurally complex analogues. Docking studies highlight an on-off conversion of the unnatural substrates.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 399
TI  - Multicomponent functionalization of the octreotide peptide macrocyclic scaffold
JO  - Eur. J. Org. Chem.
PY  - 2022
SP  - e202200687
AU  - Vasco, A. V.
AU  - Ceballos, L. G.
AU  - Wessjohann, L. A.
AU  - Rivera, D. G.
AU  - 
VL  - 2022
UR  - https://doi.org/10.1002/ejoc.202200687
DO  - 10.1002/ejoc.202200687
AB  - The replacement of the disulfide bridge by other types of side chain linkages has been a continuous endeavor in the development of cyclic peptide drugs with improved metabolic stability. Octreotide is a potent and selective somatostatin analog that has been used as an anticancer agent, in radiolabeled conjugates for the localization of tumors and as targeting moiety in peptide-drug conjugates. Here, we describe an onresin methodology based on a multicomponent macrocyclization that enables the substitution of the disulfide bond by a tertiary lactam bridge functionalized with a variety of exocyclic moieties, including lipids, fluorophores, and charged groups. Conformational analysis in comparison with octreotide provides key information on the type of functionalization permitting the conformational mimicry of the bioactive peptide.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 398
TI  - Psidium guajava L. an incalculable but underexplored food crop: Its phytochemistry, ethnopharmacology, and industrial applications
JO  - Molecules
PY  - 2022
SP  - 7016
AU  - Tousif, M. I.
AU  - Nazir, M.
AU  - Saleem, M.
AU  - Tauseef, S.
AU  - Shafiq, N.
AU  - Hassan, L.
AU  - Hussain, H.
AU  - Montesano, D.
AU  - Naviglio, D.
AU  - Zengin, G.
AU  - Ahmad, I.
AU  - 
VL  - 27
UR  - https://doi.org/10.3390/molecules27207016
DO  - 10.3390/molecules27207016
AB  - Psidium guajava L. (guava) is a small tree known for its fruit flavor that is cultivated almost around the globe in tropical areas. Its fruit is amazingly rich in antioxidants, vitamin C, potassium, and dietary fiber. In different parts of the world, this plant holds a special place with respect to fruit and nutritional items. Pharmacological research has shown that this plant has more potential than just a fruit source; it also has beneficial effects against a variety of chronic diseases due to its rich nutritional and phytochemical profile. The primary goal of this document is to provide an updated overview of Psidium guajava L. and its bioactive secondary metabolites, as well as their availability for further study, with a focus on the health benefits and potential industrial applications. There have been several studies conducted on Psidium guajava L. in relation to its use in the pharmaceutical industry. However, its clinical efficacy and applications are still debatable. Therefore, in this review a detailed study with respect to phytochemistry of the plant through modern instruments such as GC and LC-MS has been discussed. The biological activities of secondary metabolites isolated from this plant have been extensively discussed. In order to perform long-term clinical trials to learn more about their effectiveness as drugs and applications for various health benefits, a structure activity relationship has been established. Based on the literature, it is concluded that this plant has a wide variety of biopharmaceutical applications. As a whole, this article calls for long-term clinical trials to obtain a greater understanding of how it can be used to treat different diseases.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 320
TI  - Polar substitutions on the surface of a lipase substantially improve tolerance in organic solvents
JO  - ChemSusChem
PY  - 2022
SP  - e202102551
AU  - Cui, H.
AU  - Vedder, M.
AU  - Zhang, L.
AU  - Jaeger, K.-E.
AU  - Schwaneberg, U.
AU  - Davari, M. D.
AU  - 
VL  - 15
UR  - https://doi.org/10.1002/cssc.202102551
DO  - 10.1002/cssc.202102551
AB  - Biocatalysis in organic solvents (OSs) enables more efficient routes to the synthesis of various valuable chemicals. However, OSsoften reduce enzymatic activity which limits the use enzymes in OSs. Herein, we report a comprehensive understanding of interactions between surface polar substitutions and DMSO by integrating the molecular dynamics (MD) simulations of 45 variants from Bacillus subtilis lipase A (BSLA) and substitution landscape in “BSLA-SSM” library. By systematically analyzing 39 structural-, solvation-, and interaction energy-based observables, we discovered hydration shell maintenance, DMSO reduction, and decreased local flexibility simultaneously govern the stability of polar variantsin OS. Moreover,  the fingerprints of 1644 polar-related variants in three OSs demonstrated that substituting aromatic to polarresidue(s) hold great potential to highly improve OSs resistance. Hence, surface polar engineering is a powerful strategy togenerate OS-tolerant  lipases  and  other  enzymes, thereby adapting  the catalyst to the desired reaction and process with OSs.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 319
TI  - Enzyme hydration: How to retain resistance in ionic liquids
JO  - ACS Sustainable Chemistry &amp; Engineering
PY  - 2022
SP  - 15104-15114
AU  - Cui, H.
AU  - Zhang, L.
AU  - Yildiz, C. B.
AU  - Eltoukhy, L.
AU  - Cheng, L.
AU  - Jaeger, K.-E.
AU  - Schwaneberg, U.
AU  - Davari, M. D.
AU  - 
VL  - 10
UR  - https://doi.org/10.1021/acssuschemeng.2c04216
DO  - 10.1021/acssuschemeng.2c04216
AB  - Application of ionic liquids (ILs) as media in biocatalysis has enormous potential for synthesizing valuable compounds and bulk products in pharmaceuticals and bioenergy due to their unique solvent properties such as volatility, flammability, and solubility. However, ILs as reaction media are often limited by poor enzymatic activity and stability in ILs. We printed a comprehensive IL−enzyme interaction map by studying 45 molecular observables of 30 lipase A from Bacillus subtilis (BSLA) variants in four ILs and a substitutional landscape with 1504 BSLA variants. The results demonstrated that the enzyme hydration shell is the deciding and independent factor determining the enzyme’s IL resistance. A universal positive correlation (up to R2 = 0.96 in 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIM][TfO]) and R2 = 0.85 in 1-butyl-3-methylimidazolium chloride ([BMIM]Cl)) was verified, and an experimentally derived ranking of amino acid substitutions is summarized in a list to provide benefits for better protein engineering practice. Hydration-guided engineering yielded a supremely tolerant BSLA variant I12R/D34K/A132K with 8.1-fold, 8.6-fold, 6.6-fold, and 4.6-fold improved tolerance toward [BMIM]Cl, [BMIM]Br, [BMIM]I, and [BMIM][TfO], respectively, when compared to the wild-type BSLA. The obtained knowledge provides a lesson learned on forecasting enzyme stability in ILs and simplifies a rational design of the IL-tolerant enzymes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 315
TI  - Bioactive phenolic compounds from Peperomia obtusifolia
JO  - Molecules
PY  - 2022
SP  - 4363
AU  - Bin Ware, I.
AU  - Franke, K.
AU  - Hussain, H.
AU  - Morgan, I.
AU  - Rennert, R.
AU  - Wessjohann, L. A.
AU  - 
VL  - 27
UR  - https://doi.org/10.3390/molecules27144363
DO  - 10.3390/molecules27144363
AB  - Peperomia obtusifolia (L.) A. Dietr., native to Middle America, is an ornamental plant also traditionally used for its mild antimicrobial properties. Chemical investigation on the leaves of P. obtusifolia resulted in the isolation of two previously undescribed compounds, named peperomic ester (1) and peperoside (2), together with five known compounds, viz. N-[2-(3,4-dihydroxyphenyl)ethyl]-3,4-dihydroxybenzamide (3), becatamide (4), peperobtusin A (5), peperomin B (6), and arabinothalictoside (7). The structures of these compounds were elucidated by 1D and 2D NMR techniques and HREIMS analyses. Compounds 1–7 were evaluated for their anthelmintic (against Caenorhabditis elegans), antifungal (against Botrytis cinerea, Septoria tritici and Phytophthora infestans), antibacterial (against Bacillus subtilis and Aliivibrio fischeri), and antiproliferative (against PC-3 and HT-29 human cancer cell lines) activities. The known peperobtusin A (5) was the most active compound against the PC-3 cancer cell line with IC50 values of 25.6 µM and 36.0 µM in MTT and CV assays, respectively. This compound also induced 90% inhibition of bacterial growth of the Gram-positive B. subtilis at a concentration of 100 µM. In addition, compound 3 showed anti-oomycotic activity against P. infestans with an inhibition value of 56% by using a concentration of 125 µM. However, no anthelmintic activity was observed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 314
TI  - In silico and experimental ADAM17 kinetic modeling as basis for future screening system for modulators
JO  - Int. J. Mol. Sci.
PY  - 2022
SP  - 1368
AU  - Bienstein, M.
AU  - Minond, D.
AU  - Schwaneberg, U.
AU  - Davari, M. D.
AU  - Yildiz, D.
AU  - 
VL  - 23
UR  - https://doi.org/10.3390/ijms23031368
DO  - 10.3390/ijms23031368
AB  - Understanding the mechanisms of modulators’ action on enzymes is crucial for optimizing and designing pharmaceutical substances. The acute inflammatory response, in particular, is regulated mainly by a disintegrin and metalloproteinase (ADAM) 17. ADAM17 processes several disease mediators such as TNFα and APP, releasing their soluble ectodomains (shedding). A malfunction of this process leads to a disturbed inflammatory response. Chemical protease inhibitors such as TAPI-1 were used in the past to inhibit ADAM17 proteolytic activity. However, due to ADAM17′s broad expression and activity profile, the development of active-site-directed ADAM17 inhibitor was discontinued. New ‘exosite’ (secondary substrate binding site) inhibitors with substrate selectivity raised the hope of a substrate-selective modulation as a promising approach for inflammatory disease therapy. This work aimed to develop a high-throughput screen for potential ADAM17 modulators as therapeutic drugs. By combining experimental and in silico methods (structural modeling and docking), we modeled the kinetics of ADAM17 inhibitor. The results explain ADAM17 inhibition mechanisms and give a methodology for studying selective inhibition towards the design of pharmaceutical substances with higher selectivity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 313
TI  - The loss of polyphenol oxidase function is associated with hilum pigmentation and has been selected during pea domestication
JO  - New Phytol.
PY  - 2022
SP  - 1807–1821
AU  - Balarynová, J.
AU  - Klčová, B.
AU  - Sekaninová, J.
AU  - Kobrlová, L.
AU  - Cechová, M. Z.
AU  - Krejčí, P.
AU  - Leonova, T.
AU  - Gorbach, D.
AU  - Ihling, C.
AU  - Smržová, L.
AU  - Trněný, O.
AU  - Frolov, A.
AU  - Bednář, P.
AU  - Smýkal, P.
AU  - 
VL  - 235
UR  - https://doi.org/10.1111/nph.18256
DO  - 10.1111/nph.18256
AB  - Seed coats serve as protective tissue to the enclosed embryo. As well as mechanical there are also chemical defence functions. During domestication, the property of the seed coat was altered including the removal of the seed dormancy. We used a range of genetic, transcriptomic, proteomic and metabolomic approaches to determine the function of the pea seed polyphenol oxidase (PPO) gene. Sequencing analysis revealed one nucleotide insertion or deletion in the PPO gene, with the functional PPO allele found in all wild pea samples, while most cultivated peas have one of the three nonfunctional ppo alleles. PPO functionality cosegregates with hilum pigmentation. PPO gene and protein expression, as well as enzymatic activity, was downregulated in the seed coats of cultivated peas. The functionality of the PPO gene relates to the oxidation and polymerisation of gallocatechin in the seed coat. Additionally, imaging mass spectrometry supports the hypothesis that hilum pigmentation is conditioned by the presence of both phenolic precursors and sufficient PPO activity. Taken together these results indicate that the nonfunctional polyphenol oxidase gene has been selected during pea domestication, possibly due to better seed palatability or seed coat visual appearance.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 326
TI  - Medicinal plant preparations administered by Botswana traditional health practitioners for treatment of worm infections show anthelmintic activities
JO  - Plants
PY  - 2022
SP  - 2945
AU  - Dube, M.
AU  - Raphane, B.
AU  - Sethebe, B.
AU  - Seputhe, N.
AU  - Tiroyakgosi, T.
AU  - Imming, P.
AU  - Häberli, C.
AU  - Keiser, J.
AU  - Arnold, N.
AU  - Andrae-Marobela, K.
AU  - 
VL  - 11
UR  - https://doi.org/10.3390/plants11212945
DO  - 10.3390/plants11212945
AB  - Schistosomiasis and soil-transmitted helminths are some of the priority neglected tropical diseases (NTDs) targeted for elimination by the World Health Organization (WHO). They are prevalent in Botswana and although Botswana has begun mass drug administration with the hope of eliminating soil-transmitted helminths as a public health problem, the prevalence of schistosomiasis does not meet the threshold required to warrant large-scale interventions. Although Botswana has a modern healthcare system, many people in Botswana rely on traditional medicine to treat worm infections and schistosomiasis. In this study, ten plant species used by traditional health practitioners against worm infections were collected and tested against Ancylostoma ceylanicum (zoonotic hookworm), Heligmosomoides polygyrus (roundworm of rodents), Necator americanus (New World hookworm), Schistosoma mansoni (blood fluke) [adult and newly transformed schistosomula (NTS)], Strongyloides ratti (threadworm) and Trichuris muris (nematode parasite of mice) in vitro. Extracts of two plants, Laphangium luteoalbum and Commiphora pyaracanthoides, displayed promising anthelmintic activity against NTS and adult S. mansoni, respectively. L. luteoalbum displayed 85.4% activity at 1 μg/mL against NTS, while C. pyracanthoides displayed 78.5% activity against adult S. mansoni at 10 μg/mL.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 325
TI  - Albatrellus confluens (Alb. &amp; Schwein.) Kotl. &amp; Pouz.: Natural fungal compounds and synthetic derivatives with in vitro anthelmintic activities and antiproliferative effects against two human cancer cell lines
JO  - Molecules
PY  - 2022
SP  - 2950
AU  - Dube, M.
AU  - Llanes, D.
AU  - Saoud, M.
AU  - Rennert, R.
AU  - Imming, P.
AU  - Häberli, C.
AU  - Keiser, J.
AU  - Arnold, N.
AU  - 
VL  - 27
UR  - https://doi.org/10.3390/molecules27092950
DO  - 10.3390/molecules27092950
AB  - Neglected tropical diseases affect the world’s poorest populations with soil-transmitted helminthiasis and schistosomiasis being among the most prevalent ones. Mass drug administration is currently the most important control measure, but the use of the few available drugs is giving rise to increased resistance of the parasites to the drugs. Different approaches are needed to come up with new therapeutic agents against these helminths. Fungi are a source of secondary metabolites, but most fungi remain largely uninvestigated as anthelmintics. In this report, the anthelmintic activity of Albatrellus confluens against Caenorhabditis elegans was investigated using bio-assay guided isolation. Grifolin (1) and neogrifolin (2) were identified as responsible for the anthelmintic activity. Derivatives 4–6 were synthesized to investigate the effect of varying the prenyl chain length on anthelmintic activity. The isolated compounds 1 and 2 and synthetic derivatives 4–6, as well as their educts 7–10, were tested against Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum. Prenyl-2-orcinol (4) and geranylgeranyl-2-orcinol (6) showed promising activity against newly transformed schistosomula. The compounds 1, 2, 4, 5, and 6 were also screened for antiproliferative or cytotoxic activity against two human cancer lines, viz. prostate adenocarcinoma cells (PC-3) and colorectal adenocarcinoma cells (HT-29). Compound 6 was determined to be the most effective against both cell lines with IC50 values of 16.1 µM in PC-3 prostate cells and 33.7 µM in HT-29 colorectal cells.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 324
TI  - Altering the regiospecificity of a catechol
            O‐methyltransferase through rational design: Vanilloid vs. isovanilloid motifs in the B‐ring of flavonoids
JO  - ChemCatChem
PY  - 2022
SP  - e202200511
AU  - Dippe, M.
AU  - Davari, M. D.
AU  - Weigel, B.
AU  - Heinke, R.
AU  - Vogt, T.
AU  - Wessjohann, L. A.
AU  - 
VL  - 14
UR  - https://doi.org/10.1002/cctc.202200511
DO  - 10.1002/cctc.202200511
AB  - Rational re-design of the substrate pocket of phenylpropanoid-flavonoid O-methyltransferase (PFOMT) from Mesembryanthe-mum crystallinum, an enzyme that selectively methylates the 3’-position (= meta-position) in catechol-moieties of flavonoids to guiacol-moieties, provided the basis for the generation of variants with opposite, i. e. 4’- (para-) regioselectivity and enhanced catalytic efficiency. A double variant (Y51R/N202W) identified through a newly developed colorimetric assay efficiently modified the para-position in flavanone and flavano-nol substrates, providing access to the sweetener molecule hesperetin and other rare plant flavonoids having an isovanil-loid motif.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 323
TI  - Multiscale approach to dairy products design
JO  - Frontiers in Chemical Engineering
PY  - 2022
SP  - 830314
AU  - Díaz-Bustamante, M. L.
AU  - Fernández-Niño, M.
AU  - Reyes, L. H.
AU  - Alvarez Solano, O. A.
AU  - 
VL  - 4
UR  - https://doi.org/10.3389/fceng.2022.830314
DO  - 10.3389/fceng.2022.830314
AB  - Dairy products are among the most popular nutritious foods in the world. Understanding the relationship between the composition, process, and structural properties at different scales (molecular, microscopic, and macroscopic) is fundamental to designing dairy products. This review highlights the need to analyze this relationship from different scales as an essential step during product design through a multiscale approach.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 322
TI  - ERp57 chaperon protein protects neuronal cells from Aβ‐induced toxicity
JO  - Journal of Neurochemistry
PY  - 2022
SP  - 322-336
AU  - Di Risola, D.
AU  - Ricci, D.
AU  - Marrocco, I.
AU  - Giamogante, F.
AU  - Grieco, M.
AU  - Francioso, A.
AU  - Vasco‐Vidal, A.
AU  - Mancini, P.
AU  - Colotti, G.
AU  - Mosca, L.
AU  - Altieri, F.
AU  - 
VL  - 162
UR  - https://doi.org/10.1111/jnc.15655
DO  - 10.1111/jnc.15655
AB  - Alzheimer’s disease (AD) is a neurodegenerative disorder whose main pathological hallmark is the accumulation of Amyloid-β peptide (Aβ) in the form of senile plaques. Aβ can cause neurodegeneration and disrupt cognitive functions by several mechanisms, including oxidative stress. ERp57 is a protein disulfide isomerase involved in the cellular stress response and known to be present in the cerebrospinal fluid of normal individuals as a complex with Aβ peptides, suggesting that it may be a carrier protein which prevents aggregation of Aβ. Although several studies show ERp57 involvement in neurodegenerative diseases, no clear mechanism of action has been identified thus far. In this work we gain insights into the interaction of Aβwith ERp57, with a special focus on the contribution of ERp57 to the defence system of the cell. Here we show that recombinant ERp57 directly interacts with the Aβ25-35 fragment in vitro with high affinityvia two in silico-predicted main sites of interaction. Furthermore, we used human neuroblastoma cells to show that short-term Aβ25-35 treatment induces ERp57 decrease in intracellular protein levels, different intracellular localization and ERp57 secretion in the cultured medium. Finally, we demonstrate that recombinant ERp57 counteracts the toxic effects of Aβ25-35 and restores cellular viability, by preventing Aβ25-35 aggregation. Overall, the present study shows thatextracellular ERp57 can exert a protective effect from Aβ toxicity and highlights it as a possible therapeutic tool in the treatment of AD.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 10
TI  - Ligation, Macrocyclization, and Simultaneous Functionalization of Peptides by Multicomponent Reactions (MCR)
T2  - Peptide Macrocycles
PB  - Methods Mol. Biol.
PY  - 2022
SP  - 143-157
AU  - Vasco, A. V.
AU  - Ricardo, M. G.
AU  - Rivera, D. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 2371
UR  - https://doi.org/10.1007/978-1-0716-1689-5_8
SN  - 978-1-0716-1688-8
DO  - 10.1007/978-1-0716-1689-5_8
AB  - Multicomponent reactions (MCRs) are recently expanding the plethora of 
solid-phase protocols for the synthesis and derivatization of peptides. 
Herein, we describe a solid-phase-compatible strategy based on MCRs as a
 powerful strategy for peptide cyclization and ligation . We illustrate,
 using Gramicidin S as a model peptide, how the execution of on-resin 
Ugi reactions enables the simultaneous backbone N-functionalization and 
cyclization, which are important types of derivatizations in 
peptide-based drug development or for incorporation of conjugation 
handles, or labels.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 6
TI  - Fruitful decade of Phoma secondary metabolites from 2011 to 2020: Chemistry, chemical diversity, and biological activities
T2  - 
PB  - Phoma: Diversity, Taxonomy, Bioactivities, and Nanotechnology
PY  - 2022
SP  - 183–203
AU  - Hussain, H.
AU  - Elizbit, .
AU  - Ali, I.
AU  - Mamadalieva, N. Z.
AU  - Abbas, G.
AU  - Ali, M.
AU  - Zaman, G.
AU  - Khan, A.
AU  - Hassan, U.
AU  - Green, I. R.
AU  - 
VL  - 
UR  - https://doi.org/10.1007/978-3-030-81218-8_10
SN  - 978-3-030-81217-1
DO  - 10.1007/978-3-030-81218-8_10
AB  - Fungi have been an extraordinary area of scientific research, and many secondary metabolites with intriguing chemical diversity along with interesting biological activities have been identified. Fungi like Phoma sp. have been investigated as a source of structurally unique metabolites over the past 10 years (2011–2020). A diverse range of natural products, viz., α-pyrone derivatives, isocoumarins, anthraquinones, xanthones, thiodiketopiperazines, cytochalasin derivatives, diphenyl ether derivatives, furopyrans, xyloketals, chromones, meroterpenoids, diterpenoids, polyketides, and alkaloids, have been reported from various Phoma spp. These metabolites illustrated phytotoxic, cytotoxic, antibacterial, antifungal, herbicidal, immunosuppressive, antiviral, antidiabetic (PTP1B inhibition), anti-Alzheimer (acetylcholinesterase inhibition), and antioxidant activities.
A2  - Rai, M., Zimowska, B., Kövics, G.J.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 5
TI  - Introductory chapter: From BioBricks to synthetic genomes
T2  - 
PB  - Synthetic Genomics - From BioBricks to Synthetic Genomes
PY  - 2022
SP  - 
AU  - Humberto Reyes, L.
AU  - Fernández-Niño, M.
AU  - 
VL  - 
UR  - http://dx.doi.org/10.5772/intechopen.101949
SN  - 978-1-83969-638-1
DO  - 10.5772/intechopen.101949
AB  - 
A2  - Miguel Fernández-Niño, Luis H. Reyes
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 4
TI  - Engineering microbial biofactories for a sustainable future
T2  - 
PB  - Genomics and the Global Bioeconomy
PY  - 2022
SP  - 25-58
AU  - Fernández-Niño, M.
AU  - Daniela, B.-T.
AU  - 
VL  - 
UR  - https://doi.org/10.1016/B978-0-323-91601-1.00003-1
DO  - 10.1016/B978-0-323-91601-1.00003-1
AB  - Engineering microbial biofactories for the transformation of industrial residues into value-added products represents a significant step toward sustainability. This chapter has two main goals: first, to review the current approaches that can be used to engineer synthetic biofactories of relevance for white biotechnology, and second, to provide clear examples of how these biofactories represent an excellent platform to transform industrial residues into value-added products. Several technologies used to engineer microbial biofactories (e.g., BioBricks design, pathway engineering, modular assembly, and chassis fine-tuning) will be discussed using a multiscale approach from genes to biofactories. The relevance of omics databases for the identification of novel biological components (genome mining) and fine-tuning their expression will also be discussed. Finally, several examples will be provided to highlight the relevance of engineering microorganisms as biofactories for a sustainable future.
A2  - Catalina Lopez-Correa and Adriana Suarez-Gonzalez
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 3
TI  - Solid-phase heterocycle synthesis using multicomponent reactions
T2  - 
PB  - Multicomponent Reactions towards Heterocycles: Concepts and Applications
PY  - 2022
SP  - 139-162
AU  - Ceballos, L. G.
AU  - Pacheco, D. F.
AU  - Westermann, B.
AU  - Garcia-Rivera, D.
AU  - 
VL  - 4
UR  - https://doi.org/10.1002/9783527832439.ch4
SN  - 9783527349081
DO  - 10.1002/9783527832439.ch4
AB  - Heterocycle chemistry has traditionally relied on solution-phase synthesis as technological platform to discover and produce bioactive scaffolds. With the advent of solid-phase synthesis (SPS) at the end of last century, combinatorial approaches using on-resin procedures were applied to create skeletal and appendage diversity in heterocyclic compounds. Multicomponent reactions (MCRs) were part of that endeavor for developing solid-phase protocols capable to accelerate drug discovery. This chapter highlights methodological aspects of the implementation of on-resin MCRs to produce heterocycle compounds. Different name reactions, synthetic strategies, and solid supports are analyzed with a critical view hoping to encourage the new generation of chemists to adapt the more recent multicomponent – especially catalytic – processes to the SPS technology.
A2  - Erik Van der Eycken, Upendra K. Sharma
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 490
TI  - Computational Applications in Secondary Metabolite Discovery (CAiSMD): an online workshop
JO  - J. Cheminform.
PY  - 2021
SP  - 64
AU  - Ntie-Kang, F.
AU  - Telukunta, K. K.
AU  - Fobofou, S. A. T.
AU  - Chukwudi Osamor, V.
AU  - Egieyeh, S. A.
AU  - Valli, M.
AU  - Djoumbou-Feunang, Y.
AU  - Sorokina, M.
AU  - Stork, C.
AU  - Mathai, N.
AU  - Zierep, P.
AU  - Chávez-Hernández, A. L.
AU  - Duran-Frigola, M.
AU  - Babiaka, S. B.
AU  - Tematio Fouedjou, R.
AU  - Eni, D. B.
AU  - Akame, S.
AU  - Arreyetta-Bawak, A. B.
AU  - Ebob, O. T.
AU  - Metuge, J. A.
AU  - Bekono, B. D.
AU  - Isa, M. A.
AU  - Onuku, R.
AU  - Shadrack, D. M.
AU  - Musyoka, T. M.
AU  - Patil, V. M.
AU  - van der Hooft, J. J. J.
AU  - da Silva Bolzani, V.
AU  - Medina-Franco, J. L.
AU  - Kirchmair, J.
AU  - Weber, T.
AU  - Tastan Bishop, ?.
AU  - Medema, M. H.
AU  - Wessjohann, L. A.
AU  - Ludwig-Müller, J.
AU  - 
VL  - 13
UR  - https://doi.org/10.1186/s13321‑021‑00546‑8
DO  - 10.1186/s13321-021-00546-8
AB  - AbstractWe report the major conclusions of the online open-access workshop “Computational Applications in Secondary Metabolite Discovery (CAiSMD)” that took place from 08 to 10 March 2021. Invited speakers from academia and industry and about 200 registered participants from five continents (Africa, Asia, Europe, South America, and North America) took part in the workshop. The workshop highlighted the potential applications of computational methodologies in the search for secondary metabolites (SMs) or natural products (NPs) as potential drugs and drug leads. During 3 days, the participants of this online workshop received an overview of modern computer-based approaches for exploring NP discovery in the “omics” age. The invited experts gave keynote lectures, trained participants in hands-on sessions, and held round table discussions. This was followed by oral presentations with much interaction between the speakers and the audience. Selected applicants (early-career scientists) were offered the opportunity to give oral presentations (15 min) and present posters in the form of flash presentations (5 min) upon submission of an abstract. The final program available on the workshop website (https://caismd.indiayouth.info/) comprised of 4 keynote lectures (KLs), 12 oral presentations (OPs), 2 round table discussions (RTDs), and 5 hands-on sessions (HSs). This meeting report also references internet resources for computational biology in the area of secondary metabolites that are of use outside of the workshop areas and will constitute a long-term valuable source for the community. The workshop concluded with an online survey form to be completed by speakers and participants for the goal of improving any subsequent editions.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 489
TI  - Meroterpenoids: A comprehensive update insight on structural diversity and biology
JO  - Biomolecules
PY  - 2021
SP  - 957
AU  - Nazir, M.
AU  - Saleem, M.
AU  - Tousif, M. I.
AU  - Anwar, M. A.
AU  - Surup, F.
AU  - Ali, I.
AU  - Wang, D.
AU  - Mamadalieva, N. Z.
AU  - Alshammari, E.
AU  - Ashour, M. L.
AU  - Ashour, A. M.
AU  - Ahmed, I.
AU  - Elizbit, .
AU  - Green, I. R.
AU  - Hussain, H.
AU  - 
VL  - 11
UR  - https://www.mdpi.com/2218-273X/11/7/957
DO  - 10.3390/biom11070957
AB  - Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 488
TI  - Fungal metabolites as anti-diabetic agents: emphasison PTP1B inhibitors
JO  - Phytochemistry
PY  - 2021
SP  - 119-143
AU  - Nazir, M.
AU  - Saleem, M.
AU  - Ali, I.
AU  - Abbas, G.
AU  - Rehman, N. U.
AU  - Green, I. R.
AU  - Hussain, W.
AU  - Khan, S.
AU  - Hussain, H.
AU  - 
VL  - 20
UR  - https://link.springer.com/article/10.1007/s11101-020-09701-9
DO  - 10.1007/s11101-020-09701-9
AB  - In the last decade the prevalence of diabetes has escalated globally and it is estimated that the number of diabetic people will increase to 642 million by 2040. Although numerous classes of pharmaceutical drugs are available to treat Type ll diabetes, they manifest certain side effects. PTP1B has attracted significant interest as an important therapeutic agent and has been validated to target diabetes and obesity. Fungi, in general, produce secondary metabolites with some amazing chemical and structural diversity and are recognized to be a valuable source for therapeutic molecules. In this review, the focus is on describing the PTP1B effects and their potential as anti-diabetic agents for the various metabolites isolated from fungi.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 487
TI  - C@PA: Computer-aided pattern analysis to predict multitarget ABC transporter inhibitors
JO  - J. Med. Chem.
PY  - 2021
SP  - 3350-3366
AU  - Namasivayam, V.
AU  - Silbermann, K.
AU  - Wiese, M.
AU  - Pahnke, J.
AU  - Stefan, S. M.
AU  - 
VL  - 64
UR  - 
DO  - 10.1021/acs.jmedchem.0c02199
AB  - Based on literature reports of the last two decades, a computer-aided pattern analysis (C@PA) was implemented for the discovery of novel multitarget ABCB1 (P-gp), ABCC1 (MRP1), and ABCG2 (BCRP) inhibitors. C@PA
 included basic scaffold identification, substructure search and 
statistical distribution, as well as novel scaffold extraction to screen
 a large virtual compound library. Over 45,000 putative and novel 
broad-spectrum ABC transporter inhibitors were identified, from which 23
 were purchased for biological evaluation. Our investigations revealed 
five novel lead molecules as triple ABCB1, ABCC1, and ABCG2 inhibitors. C@PA is the very first successful computational approach for the discovery of promiscuous ABC transporter inhibitors.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 484
TI  - pH-responsive release of ruthenium metallotherapeutics from mesoporous silica-based nanocarriers
JO  - Pharmaceutics
PY  - 2021
SP  - 460
AU  - Mladenović, M.
AU  - Morgan, I.
AU  - Ilić, N.
AU  - Saoud, M.
AU  - Pergal, M. V.
AU  - Kaluderović, G. N.
AU  - Knežević, N. ?.
AU  - 
VL  - 13
UR  - https://www.mdpi.com/1999-4923/13/4/460
DO  - 10.3390/pharmaceutics13040460
AB  - Ruthenium complexes are attracting interest in cancer treatment due to their potent cytotoxic activity. However, as their high toxicity may also affect healthy tissues, efficient and selective drug delivery systems to tumour tissues are needed. Our study focuses on the construction of such drug delivery systems for the delivery of cytotoxic Ru(II) complexes upon exposure to a weakly acidic environment of tumours. As nanocarriers, mesoporous silica nanoparticles (MSN) are utilized, whose surface is functionalized with two types of ligands, (2-thienylmethyl)hydrazine hydrochloride (H1) and (5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)hydrazine (H2), which were attached to MSN through a pH-responsive hydrazone linkage. Further coordination to ruthenium(II) center yielded two types of nanomaterials MSN-H1[Ru] and MSN-H2[Ru]. Spectrophotometric measurements of the drug release kinetics at different pH (5.0, 6.0 and 7.4) confirm the enhanced release of Ru(II) complexes at lower pH values, which is further supported by inductively coupled plasma optical emission spectrometry (ICP-OES) measurements. Furthermore, the cytotoxicity effect of the released metallotherapeutics is evaluated in vitro on metastatic B16F1 melanoma cells and enhanced cancer cell-killing efficacy is demonstrated upon exposure of the nanomaterials to weakly acidic conditions. The obtained results showcase the promising capabilities of the designed MSN nanocarriers for the pH-responsive delivery of metallotherapeutics and targeted treatment of cancer.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 478
TI  - Analysis of Unusual Sulfated Constituents and Anti-infective Properties of Two Indonesian Mangroves, Lumnitzera littorea and Lumnitzera racemosa (Combretaceae)
JO  - Separations
PY  - 2021
SP  - 82
AU  - Manurung, J.
AU  - Kappen, J.
AU  - Schnitzler, J.
AU  - Frolov, A.
AU  - Wessjohann, L. A.
AU  - Agusta, A.
AU  - Muellner-Riehl, A. N.
AU  - Franke, K.
AU  - 
VL  - 8
UR  - https://www.mdpi.com/2297-8739/8/6/82
DO  - 10.3390/separations8060082
AB  - Lumnitzera littorea and Lumnitzera racemosa are mangrove species distributed widely along the Indonesian coasts. Besides their ecological importance, both are of interest owing to their wealth of natural products, some of which constitute potential sources for medicinal applications. We aimed to discover and characterize new anti-infective compounds, based on population-level sampling of both species from across the Indonesian Archipelago. Root metabolites were investigated by TLC, hyphenated LC-MS/MS and isolation, the internal transcribed spacer (ITS) region of rDNA was used for genetic characterization. Phytochemical characterization of both species revealed an unusual diversity in sulfated constituents with 3,3’,4’-tri-O-methyl-ellagic acid 4-sulfate representing the major compound in most samples. None of these compounds was previously reported for mangroves. Chemophenetic comparison of L. racemosa populations from different localities provided evolutionary information, as supported by molecular phylogenetic evidence. Samples of both species from particular locations exhibited anti-bacterial potential (Southern Nias Island and East Java against Gram-negative bacteria, Halmahera and Ternate Island against Gram-positive bacteria). In conclusion, Lumnitzera roots from natural mangrove stands represent a promising source for sulfated ellagic acid derivatives and further sulfur containing plant metabolites with potential human health benefits.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 477
TI  - Validation of the antioxidant and enzyme inhibitory potential of selected triterpenes using in vitro and in silico studies, and the evaluation of their ADMET properties
JO  - Molecules
PY  - 2021
SP  - 6331
AU  - Mamadalieva, N. Z.
AU  - Youssef, F. S.
AU  - Hussain, H.
AU  - Zengin, G.
AU  - Mollica, A.
AU  - Al Musayeib, N. M.
AU  - Ashour, M. L.
AU  - Westermann, B.
AU  - Wessjohann, L. A.
AU  - 
VL  - 26
UR  - https://doi.org/10.3390/molecules26216331
DO  - 10.3390/molecules26216331
AB  - The antioxidant and enzyme inhibitory potential of fifteen cycloartane-type triterpenes’ potentials were investigated using different assays. In the phosphomolybdenum method, cycloalpioside D (6) (4.05 mmol TEs/g) showed the highest activity. In 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) cation radical scavenging assays, cycloorbicoside A-7-monoacetate (2) (5.03 mg TE/g) and cycloorbicoside B (10) (10.60 mg TE/g) displayed the highest activities, respectively. Oleanolic acid (14) (51.45 mg TE/g) and 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 7-monoacetate (4) (13.25 mg TE/g) revealed the highest reducing power in cupric ion-reducing activity (CUPRAC) and ferric-reducing antioxidant power (FRAP) assays, respectively. In metal-chelating activity on ferrous ions, compound 2 displayed the highest activity estimated by 41.00 mg EDTAE/g (EDTA equivalents/g). The tested triterpenes showed promising AChE and BChE inhibitory potential with 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 2′,3′,4′,7-tetraacetate (3), exhibiting the highest inhibitory activity as estimated from 5.64 and 5.19 mg GALAE/g (galantamine equivalent/g), respectively. Compound 2 displayed the most potent tyrosinase inhibitory activity (113.24 mg KAE/g (mg kojic acid equivalent/g)). Regarding α-amylase and α-glucosidase inhibition, 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol (5) (0.55 mmol ACAE/g) and compound 3 (25.18 mmol ACAE/g) exerted the highest activities, respectively. In silico studies focused on compounds 2, 6, and 7 as inhibitors of tyrosinase revealed that compound 2 displayed a good ranking score (−7.069 kcal/mole) and also that the ΔG free-binding energy was the highest among the three selected compounds. From the ADMET/TOPKAT prediction, it can be concluded that compounds 4 and 5 displayed the best pharmacokinetic and pharmacodynamic behavior, with considerable activity in most of the examined assays.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 475
TI  - Bruceadysentoside A, a new pregnane glycoside and others secondary metabolites with cytotoxic activity from brucea antidysenterica J. F. Mill. (simaroubaceae)
JO  - Nat. Prod. Res.
PY  - 2021
SP  - 2037-2043
AU  - Makong, Y. S.
AU  - Fotso, G. W.
AU  - Mouthe, G. H.
AU  - Lenta, B.
AU  - Rennert, R.
AU  - Sewald, N.
AU  - Arnold, N.
AU  - Wansi, J. D.
AU  - Ngadjui, B. T.
AU  - 
VL  - 35
UR  - https://doi.org/10.1080/14786419.2019.1655024
DO  - 10.1080/14786419.2019.1655024
AB  - The chemical investigation of the root barks leaves and stem barks of Brucea antidysenterica J. F. Mill. (Simaroubaceae) led to the isolation of a new pregnane glycoside, named Bruceadysentoside A or 3-O-β-L-arabinopyranosyl-pregn-5-en-20-one (1) together with seventeen known compounds. Their structures were established from spectral data, mainly HRESIMS, 1 D and 2 D NMR and by comparison with literature data. Compounds 1, 2, 5, 6, 8, 10, 12 and 13 were tested in vitro for their effects on the viability of two different human cancer cell lines, namely prostate PC-3 adenocarcinoma cells and colorectal HT-29 adenocarcinoma cells. No substantial activities were recorded for 2, 10, 12 and 13 (up to 10 μM concentration). 1, 5 and 8 did not show strong anti-proliferative effects up to 100 μM, however, 6 exhibited a stronger anti-proliferative effect with IC50 values of ∼ 100 μM against PC-3 and ∼ 200 μM against HT-29.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 474
TI  - A simple and efficient two-dimensional high-speed counter-current chromatography linear gradient and isocratic elution modes for the preparative separation of coumarins from roots of Toddalia asiatica (Linn.) Lam.
JO  - Molecules
PY  - 2021
SP  - 5986
AU  - Ma, W.
AU  - Ali, I.
AU  - Li, Y.
AU  - Hussain, H.
AU  - Zhao, H.
AU  - Sun, X.
AU  - Xie, L.
AU  - Cui, L.
AU  - Wang, D.
AU  - 
VL  - 26
UR  - https://doi.org/10.3390/molecules26195986
DO  - 10.3390/molecules26195986
AB  - Toddalia asiatica (L.) Lam. (Rutaceae) has shown a broad spectrum of biological properties, such as anti-inflammatory, antioxidant, antimicrobial, anti-HIV, and anticancer properties. The present study is concerned with the separation of the main components with broad partition coefficients (KD values) from T. asiatica, using linear gradient high-speed counter-current chromatography (LGCCC) combined with an off-line two-dimensional (2D) mode. Similar to the binary gradient HPLC, the LGCCC mode is operated by the adjustment of the proportion between the mobile phase of 5:5:1:9 (v/v) (pump A) and 5:5:4.5:5.5 (v/v) (pump B) in an n-hexane/ethyl acetate/methanol/water solvent system. The off-line 2D-CCC mode was used in this study for the secondary separation of two similar KD value compounds with n-hexane/ethyl acetate/methanol/water (5:5:4:6, v/v). Notably, six coumarins, namely, tomentin (1), toddalolactone (2), 5,7,8-trimethoxycoumarin (3), mexoticin (4), isopimpinellin (5), and toddanone (6), were efficiently separated. The structures of the pure compounds were elucidated by spectral techniques and compared with the literature.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 471
TI  - Reaction mechanism of the farnesyl pyrophosphate C-methyltransferase towards the biosynthesis of pre-sodorifen pyrophosphate by Serratia plymuthica 4Rx13
JO  - Sci. Rep.
PY  - 2021
SP  - 3182
AU  - Lemfack, M. C.
AU  - Brandt, W.
AU  - Krüger, K.
AU  - Gurowietz, A.
AU  - Djifack, J.
AU  - Jung, J.-P.
AU  - Hopf, M.
AU  - Noack, H.
AU  - Junker, B.
AU  - von Reuß, S.
AU  - Piechulla, B.
AU  - 
VL  - 11
UR  - 
DO  - 10.1038/s41598-021-82521-9
AB  - AbstractClassical terpenoid biosynthesis involves the cyclization of the linear prenyl pyrophosphate precursors geranyl-, farnesyl-, or geranylgeranyl pyrophosphate (GPP, FPP, GGPP) and their isomers, to produce a huge number of natural compounds. Recently, it was shown for the first time that the biosynthesis of the unique homo-sesquiterpene sodorifen by Serratia plymuthica 4Rx13 involves a methylated and cyclized intermediate as the substrate of the sodorifen synthase. To further support the proposed biosynthetic pathway, we now identified the cyclic prenyl pyrophosphate intermediate pre-sodorifen pyrophosphate (PSPP). Its absolute configuration (6R,7S,9S) was determined by comparison of calculated and experimental CD-spectra of its hydrolysis product and matches with those predicted by semi-empirical quantum calculations of the reaction mechanism. In silico modeling of the reaction mechanism of the FPP C-methyltransferase (FPPMT) revealed a SN2 mechanism for the methyl transfer followed by a cyclization cascade. The cyclization of FPP to PSPP is guided by a catalytic dyad of H191 and Y39 and involves an unprecedented cyclopropyl intermediate. W46, W306, F56, and L239 form the hydrophobic binding pocket and E42 and H45 complex a magnesium cation that interacts with the diphosphate moiety of FPP. Six additional amino acids turned out to be essential for product formation and the importance of these amino acids was subsequently confirmed by site-directed mutagenesis. Our results reveal the reaction mechanism involved in methyltransferase-catalyzed cyclization and demonstrate that this coupling of C-methylation and cyclization of FPP by the FPPMT represents an alternative route of terpene biosynthesis that could increase the terpenoid diversity and structural space.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 465
TI  - Overcoming Tribal Boundaries: The Biocultural Heritage of Foraging and Cooking Wild Vegetables among Four Pathan Groups in the Gadoon Valley, NW Pakistan
JO  - Biology
PY  - 2021
SP  - 537
AU  - Khan, S.
AU  - Hussain, W.
AU  - Sulaiman, .
AU  - Shah, S.
AU  - Hussain, H.
AU  - Altyar, A. E.
AU  - Ashour, M. L.
AU  - Pieroni, A.
AU  - 
VL  - 10
UR  - https://www.mdpi.com/2079-7737/10/6/537
DO  - 10.3390/biology10060537
AB  - The foraging and consumption of wild food plants is a long-standing tradition in many parts of the world and their importance in promoting food security has become more widely debated in recent years. The current study aimed to document, analyze, and interpret the traditional knowledge of non-cultivated vegetables among four Pathan tribes (Alisher Khel, Hadarzai, Haji Khel, and Umarzai) living in the Gadoon Valley, Swabi District, Khyber Pakhtunkhwa, NW Pakistan, and to evaluate how these practices vary among the considered tribal communities. A total of 104 informants were interviewed via a semi-structured, open-ended questionnaire and group discussions. The field survey was conducted from October 2018 to November 2020. Information about local names, growth habit, used plant parts, food/cooking details, medicinal perceptions, availability season, and market prices were collected. The field survey recorded 51 non-cultivated vegetables belonging to 24 botanical families, for which the frequently used plant parts included young leaves, stems, and flowers. The greatest number of use reports was recorded for Colocasia and the highest cultural index value was recorded for Rumex dentatus; the dominant botanical families were Asteraceae and Fabaceae (six species each). Seven species were found to be sold at local and regional markets. Cross-cultural analysis among the four considered tribes showed that the largest number of species was reported by members of the Hadarzai and Umarzai tribes, although most of the quoted wild vegetables were homogenously gathered among all considered communities, with some more idiosyncratic plant uses among the Umarzai group, who have likely been less affected by the erosion of traditional knowledge or possibly have had less access to traded cultivated vegetables. The novelty of the data was assessed by comparing it with the previously published wild food ethnobotanical literature of Pakistan, which showed fifteen new wild vegetables not yet reported in the NW of the country. The recorded food biocultural heritage should be seriously considered in future local development projects aimed at fostering environmental sustainability and food security.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 462
TI  - Fluorescent spherical mesoporous silica nanoparticles loaded with emodin: Synthesis, cellular uptake and anticancer activity
JO  - Mater. Sci. Eng. C-Mater. Biol. Appl.
PY  - 2021
SP  - 111619
AU  - Jänicke, P.
AU  - Lennicke, C.
AU  - Meister, A.
AU  - Seliger, B.
AU  - Wessjohann, L. A.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 119
UR  - https://doi.org/10.1016/j.msec.2020.111619
DO  - 10.1016/j.msec.2020.111619
AB  - The natural product emodin (EO) exhibits anti-inflammatory, antiangiogenesis and antineoplastic properties in vitro and in vivo. Due to its biological properties as well as its fluorescence, EO can be useful in pharmacology and pharmacokinetics. To enhance its selectivity to cancer cells, EO was loaded into non-fluorescent and novel fluorescent spherical mesoporous nanoparticles bearing N-methyl isatoic anhydride (SNM~M) or lissamine rhodamine B sulfonyl moieties (SNM~L). The propylamine functionalized mesoporous silica nanomaterial (SNM) were characterized by powder X-ray diffraction (XRD), nitrogen gas sorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), fluorescence spectroscopy, thermogravimetric analysis (TGA) and UV spectroscopy. The cytotoxicity of EO-loaded nanoparticles was tested against the human colon carcinoma cell line HT-29. Non-loaded SNM did not affect cell proliferation, whereas those loaded with EO were at least as efficient as EO alone. It could be shown by fluorescence microscopy that the uptake of silica nanomaterial by the tumor cells occurred within 2 h and the release of EO occurred within 48 h of treatment. Flow cytometry and Western blot analysis showed that SNM containing EO induced apoptosis in HT-29 cells.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 461
TI  - Studies on varying nutrient status of five plants species in pre-reproductive, reproductive and post-reproductive stages, Koh-e-Sufaid range, Kurram valley, Pakistan
JO  - Pakistan Journal of Botany
PY  - 2021
SP  - 1771-1777
AU  - Hussain, W.
AU  - Badshah, L.
AU  - Ali, A.
AU  - Hussain, H.
AU  - Hussain, F.
AU  - 
VL  - 53
UR  - http://dx.doi.org/10.30848/PJB2021-5(2)
DO  - 10.30848/pjb2021-5(2)
AB  - This study was designed to investigate the mineral composition at three phenological stages of some selected fodder forage. Therefore, five taxa viz., Indigofera gerardiana, Tagetes minutia, Rubus fruticosus, Medicago sativa, and Quercus baloot were tested for different minerals such as Mg, K, Na, Ca, Zn, Co, Fe, Cr, Mn and Cu. The highest concentration of macronutrients i.e. Ca (96700 µg/g), Mn (99800 µg/g) were found at post-reproductive phase in Indigofera gerardiana and K (90200 µg/g) was recorded during pre-reproductive phase in Tagetes minutia while the Rubus fruticosus exhibited (17800µg/g) and (59900µg/g) Co and Cu respectively. Similarly, the highest level of Chromium (Cr) recorded (76600µg/g) at reproductive phase in Tagetes minuta, Nickle concentration was recorded maximum i.e. 46400 µg/g at pre-reproductive phase in Rubus fruticosus. Furthermore, Zn contents were (88800 µg/g) at pre-reproductive both in Medicago sativa and Tagetes minuta and subsequently Fe (59300 µg/g) at pre-reproductive phase in Indigofera gerardiana. This study helped in correlating the mineral status of these plant species to their palatability status. The mineral profile of the plants analyzed indicates that mineral levels were as per the required standards and their concentrations were not drastically different from other parts of Pakistan.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 460
TI  - Glycyrrhetinic acid: a promising scaffold for the discovery of anticancer agents
JO  - Expert Opinion on Drug Discovery
PY  - 2021
SP  - 1497-1516
AU  - Hussain, H.
AU  - Ali, I.
AU  - Wang, D.
AU  - Hakkim, F. L.
AU  - Westermann, B.
AU  - Ahmed, I.
AU  - Ashour, A. M.
AU  - Khan, A.
AU  - Hussain, A.
AU  - Green, I. R.
AU  - Shah, S. T. A.
AU  - 
VL  - 16
UR  - https://doi.org/10.1080/17460441.2021.1956901
DO  - 10.1080/17460441.2021.1956901
AB  - Introduction: Oleanane-type pentacyclic triterpenes named glycyrrhetinic acids (GAs) featuring a C-30 carboxylic acid group, are extracted from the licorice (Glycyrrhiza uralensis). Numerous biological properties of GA have been reported and have attracted researchers from all over the world in recent years due to the peculiar GA scaffold-based semisynthetic cytotoxic effects.Areas covered: This review represents the applications of semisynthetic derivatives of GA for the development of future cancer treatments. Included in the review are important structural features of the semisynthetic GAs crucial for cytotoxic effects.Expert opinion: Numerous semisynthetic GA derivatives illustrated excellent cytotoxic effects toward various cancer cells. Notably the C-3(OH) at ring A along with C30-CO2H at ring E as vital structural features, make GA very appealing as a lead scaffold for medicinal chemistry, since these two groups permit the creation of further chemical diversity geared toward improved cytotoxic effects. Furthermore, numerous GA derivatives have been synthesized and indicate that compounds featuring cyanoenone moieties in ring A, or compounds having the amino group or nitrogen comprising heterocycles and hybrids thereof, illustrate more potent cytotoxicity. Furthermore, GA has a great capability to be conjugated with other anticancer molecules to synergistically enhance their combined cytotoxicity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 459
TI  - Fungal glycosides: Structure and biological function
JO  - Trends in Food Science &amp; Technology
PY  - 2021
SP  - 611-651
AU  - Hussain, H.
AU  - Mamadalieva, N. Z.
AU  - Ali, I.
AU  - Elizbit, .
AU  - Green, I. R.
AU  - Wang, D.
AU  - Zou, L.
AU  - Simal-Gandara, J.
AU  - Cao, H.
AU  - Xiao, J.
AU  - 
VL  - 110
UR  - https://doi.org/10.1016/j.tifs.2021.02.029
DO  - 10.1016/j.tifs.2021.02.029
AB  - Background: Natural products acquire vast and intriguing structural diversity and have been recognized as a tremendously diverse source of new lead compounds. Numerous bioactive secondary metabolites are present in the form of glycosylated molecules in which the sugar parts are normally associated with the interaction along with molecular recognition of the cellular target.Scope and approach: The presence of sugar entities are crucial as well as in some cases necessary, for therapeutic effects. Establishing novel and potent glycosylated secondary metabolites has formed a main goal in the natural product field from fungi and bacteria. These compounds possess a diverse range of sugar units.Key findings and conclusions: Fungi is considered one of the important sources for approved drugs with a diverse range of mode of action. The sugar part in numerous pharmacologically active natural products enhances bioavailability, biological potential, reduce toxicity, and improve stability. The vast majority of glyocosides showed antimicrobial effects, cytotoxic, antiviral and antiinflammatory effects. Notably, numerous fungal glycosides presented in this review illustrate significant antimicrobial effects towards various microorganisms especially against plant pathogens. The antimicrobial effects of these fungal glycosides indicate that these metabolites could be employed as natural preservatives in food in order to abolish or control the growth of pathogenic and spoilage microorganisms.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 458
TI  - Fruitful decade of fungal metabolites as anti-diabetic agents from 2010 to 2019: emphasis on α-glucosidase inhibitors
JO  - Phytochem. Rev.
PY  - 2021
SP  - 145-179
AU  - Hussain, H.
AU  - Nazir, M.
AU  - Saleem, M.
AU  - Al-Harrasi, A.
AU  - Elizbit, .
AU  - Green, I. R.
AU  - 
VL  - 20
UR  - https://doi.org/10.1007/s11101-020-09733-1
DO  - 10.1007/s11101-020-09733-1
AB  - AbstractIn recent years the prevalence of diabetes has increased globally and by 2040 the number of diabetic people has been estimated to increase to 642 million. Various classes of drugs are available to treat Type ll diabetes. However, these drugs are associated with certain side effects. α-Glucosidase is an intriquing target enzyme to treat Type II diabetes, and α-glucosidase inhibitors are considered as first-line drugs for Type ll patients. Fungi, in general, produce natural products with some amazing chemical diversity and many fungal metabolites have illustrated a wide range of biological and pharmacological effects. In this review the focus is on describing the α-glucosidase effects and their potential as anti-diabetic agents of various metabolites isolated from fungi.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 457
TI  - Boswellic acids: privileged structures to develop lead compounds for anticancer drug discovery
JO  - Expert Opinion on Drug Discovery
PY  - 2021
SP  - 851-867
AU  - Hussain, H.
AU  - Ali, I.
AU  - Wang, D.
AU  - Hakkim, F. L.
AU  - Westermann, B.
AU  - Rashan, L.
AU  - Ahmed, I.
AU  - Green, I. R.
AU  - 
VL  - 16
UR  - https://www.tandfonline.com/doi/full/10.1080/17460441.2021.1892640
DO  - 10.1080/17460441.2021.1892640
AB  - Introduction: Cancer has been identified to be the second major cause of death internationally as exemplified by ca. 9.6 million deaths in 2018 along with ca. 18 million new patients in 2018 that have been recorded. Natural boswellic acids (BAs) and their source, frankincense, have been reported to possess in vitro and in vivo anticancer effects toward various cancer cells.Areas covered: This comprehensive review focuses on the importance of boswellic acids (BAs) for the establishment of future treatments of cancer. Moreover, potent semisynthetic derivatives of BAs have been described along with their mode of action. In addition, important structural features of the semisynthetic BAs required for cytotoxic effects are also discussed.Expert opinion: Numerous semisynthetic BAs illustrate excellent cytotoxic effects. Of note, compounds bearing cyanoenone moieties in ring A, endoperoxides and hybrids display increased and more potent cytotoxic effects compared with other semisynthetic BAs. Moreover, BAs have the potential to conjugate or couple with other anticancer compounds to synergistically increase their combined anticancer effects. In addition, to get derived BAs to become lead anticancer compounds, future research should focus on the preparation of ring A cyanoenones, endoperoxides, and C-24 amide analogs.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 456
TI  - Separation of constituents from
            Bergenia stracheyi
            (Hook. F. &amp; Thoms.) Engl. by high‐speed countercurrent chromatography with elution mode and its antidiabetic and antioxidant in vitro evaluation
JO  - J Sep Sci
PY  - 2021
SP  - 767-776
AU  - Hou, Y.
AU  - Ali, I.
AU  - Li, Z.
AU  - Sulaiman, A.
AU  - Aziz, S.
AU  - Chen, L.
AU  - Hussain, H.
AU  - Cui, L.
AU  - Wang, D.
AU  - Zheng, X.
AU  - 
VL  - 44
UR  - https://doi.org/10.1002/jssc.202000999
DO  - 10.1002/jssc.202000999
AB  - Diabetes, a metabolic disorder, is caused by a high blood sugar level. Diabetes isan increasing health issue and search for potent antidiabetic agents is desirable.Owing to its ethnomedicinal value, the Himalayan perennial herb Bergenia stracheyi(Hook. f. &amp; Thoms.) Engl. (Saxifragaceae Juss) is used to treat diabetes.Herein, an efficient high-speed countercurrent chromatography with elutionmode is reported for separation of active compounds from B. stracheyi. In currentinvestigation, six main compounds including β-arbutin (1), bergenin (2), 6-O-galloylarbutin (3), gallic acid (4), 11-O-galloylbergenin (5), and (-)-epicatechin3-O-gallate (6) with above 95% purity were efficiently separated in a singlerun using biphasic tert-butyl methyl ether/n-butanol/methanol/water (1:3:1:5,v/v/v/v) solvent system. The structures of these compounds were characterizedusing spectral techniques and compared with the literature. Antidiabetic andantioxidant activities evaluation of the study samples showed that β-arbutin (1)and 6-O-galloylarbutin (3) have a significant protective effect, especially at highdose against hydrogen peroxide induced oxidative injury. Our results might helpfurther in-depth phytochemical and biological evaluation studies in search ofpotent antidiabetic compounds from B. stracheyi.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 454
TI  - Dissecting fine-flavor cocoa bean fermentation through metabolomics analysis to break down the current metabolic paradigm
JO  - Sci. Rep.
PY  - 2021
SP  - 21904
AU  - Herrera-Rocha, F.
AU  - Cala, M. P.
AU  - Aguirre Mejía, J. L.
AU  - Rodríguez-López, C. M.
AU  - Chica, M. J.
AU  - Olarte, H. H.
AU  - Fernández-Niño, M.
AU  - González Barrios, A. F.
AU  - 
VL  - 11
UR  - https://doi.org/10.1038/s41598-021-01427-8
DO  - 10.1038/s41598-021-01427-8
AB  - AbstractCocoa fermentation plays a crucial role in producing flavor and bioactive compounds of high demand for food and nutraceutical industries. Such fermentations are frequently described as a succession of three main groups of microorganisms (i.e., yeast, lactic acid, and acetic acid bacteria), each producing a relevant metabolite (i.e., ethanol, lactic acid, and acetic acid). Nevertheless, this view of fermentation overlooks two critical observations: the role of minor groups of microorganisms to produce valuable compounds and the influence of environmental factors (other than oxygen availability) on their biosynthesis. Dissecting the metabolome during spontaneous cocoa fermentation is a current challenge for the rational design of controlled fermentations. This study evaluates variations in the metabolic fingerprint during spontaneous fermentation of fine flavor cocoa through a multiplatform metabolomics approach. Our data suggested the presence of two phases of differential metabolic activity that correlate with the observed variations on temperature over fermentations: an exothermic and an isothermic phase. We observed a continuous increase in temperature from day 0 to day 4 of fermentation and a significant variation in flavonoids and peptides between phases. While the second phase, from day four on, was characterized for lower metabolic activity, concomitant with small upward and downward fluctuations in temperature. Our work is the first to reveal two phases of metabolic activity concomitant with two temperature phases during spontaneous cocoa fermentation. Here, we proposed a new paradigm of cocoa fermentation that considers the changes in the global metabolic activity over fermentation, thus changing the current paradigm based only on three main groups of microorganism and their primary metabolic products.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 453
TI  - Semi-quantification of lectins in rice (Oryza sativa L.) genotypes via hemagglutination
JO  - Agronomy
PY  - 2021
SP  - 1899
AU  - Gulzar, H.
AU  - Nawaz, M. A.
AU  - Jan, A.
AU  - Khan, F. A.
AU  - Naz, S.
AU  - Zahoor, M.
AU  - Naz, D.
AU  - Ullah, R.
AU  - Ali, E. A.
AU  - Hussain, H.
AU  - 
VL  - 11
UR  - https://doi.org/10.3390/agronomy11101899
DO  - 10.3390/agronomy11101899
AB  - Lectins are unique glycoproteins that react with specific sugar residues on cell surfaces resulting in agglutination. They offer enormous applications in therapeutics, diagnostics, medicine, and agriculture. Rice lectins are naturally expressed during biotic and abiotic stresses suggesting their importance in stress resistance physiology. The objective of this study was to determine the presence and relative concentration of lectins in different accessions of rice obtained from IABGR/NARC Islamabad mainly originated from Pakistan. About 210 rice accessions including 02 local varieties and 05 transgenic seeds were screened for seed lectins using a hemagglutination (HA) assay with 5% Californian bred rabbits’ erythrocytes. A protein concentration of 3–8 mg/100 mg of seed flour was measured for all the rice accessions; the highest was 8.03 mg for accession 7600, while the lowest noted was 3.05 mg for accession 7753. Out of 210 accessions, 106 showed the highest HA activity. These 106 genotypes were further screened for titer analysis and specific activity. The highest titer and specific activity were observed for accession 7271 as 1024 and 236 hemagglutination unit (HAU), respectively. The selected accessions’ relative affinity and HA capability were evaluated using blood from four different sources: human, broiler chicken, local rabbit, and Californian-breed rabbit. The highest HA activity was observed with Californian-breed rabbit RBCs. The lectin assay was stable for about 1–2 h. After the required investigations, the accessions with higher lectin concentration and HA capability could be used as a readily available source of lectins for further characterization and utilization in crop improvement programs.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 449
TI  - Probing glycation potential of dietary sugars in human blood by anintegrated in vitro approach
JO  - Food Chem.
PY  - 2021
SP  - 128951
AU  - Frolova, N.
AU  - Soboleva, A.
AU  - Nguyen, V. D.
AU  - Kim, A.
AU  - Ihling, C.
AU  - Eisenschmidt-Bönn, D.
AU  - Mamontova, T.
AU  - Herfurth, U. M.
AU  - Wessjohann, L. A.
AU  - Sinz, A.
AU  - Birkenmeyer, C.
AU  - Frolov, A.
AU  - 
VL  - 347
UR  - https://doi.org/10.1016/j.foodchem.2020.128951
DO  - 10.1016/j.foodchem.2020.128951
AB  - Glycation is referred to as the interaction of protein amino and guanidino groups with reducing sugars and carbonyl products of their degradation. Resulting advanced glycation end-products (AGEs) contribute to pathogenesis of diabetes mellitus and neurodegenerative disorders. Upon their intestinal absorption, dietary sugars and á-dicarbonyl compounds interact with blood proteins yielding AGEs. Although the differences in glycation potential of monosaccharides are well characterized, the underlying mechanisms are poorly understood. To address this question, D-glucose, D-fructose and L-ascorbic acid were incubated with human serum albumin (HSA). The sugars and á-dicarbonyl intermediates of their degradation were analyzed in parallel to protein glycation patterns (exemplified with hydroimidazolone modifications of arginine residues and products of their hydrolysis) by bottom-up proteomics and computational chemistry. Glycation of HSA with sugars revealed 9 glyoxal- and 14 methylglyoxal-derived modification sites. Their dynamics was sugar-specific and depended on concentrations of á-dicarbonyls, their formation kinetics, and presence of stabilizing residues in close proximity to the glycation sites.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 448
TI  - Highly tunable TetR-dependent target gene expression in the acetic acid bacterium Gluconobacter oxydans
JO  - Applied Microbiology and Biotechnology
PY  - 2021
SP  - 6835-6852
AU  - Fricke, P. M.
AU  - Lürkens, M.
AU  - Hünnefeld, M.
AU  - Sonntag, C. K.
AU  - Bott, M.
AU  - Davari, M. D.
AU  - Polen, T.
AU  - 
VL  - 105
UR  - https://doi.org/10.1007/s00253-021-11473-x
DO  - 10.1007/s00253-021-11473-x
AB  - Abstract
                For the acetic acid bacterium (AAB) Gluconobacter oxydans only recently the first tight system for regulatable target gene expression became available based on the heterologous repressor-activator protein AraC from Escherichia coli and the target promoter ParaBAD. In this study, we tested pure repressor-based TetR- and LacI-dependent target gene expression in G. oxydans by applying the same plasmid backbone and construction principles that we have used successfully for the araC-ParaBAD system. When using a pBBR1MCS-5-based plasmid, the non-induced basal expression of the Tn10-based TetR-dependent expression system was extremely low. This allowed calculated induction ratios of up to more than 3500-fold with the fluorescence reporter protein mNeonGreen (mNG). The induction was highly homogeneous and tunable by varying the anhydrotetracycline concentration from 10 to 200 ng/mL. The already strong reporter gene expression could be doubled by inserting the ribosome binding site AGGAGA into the 3’ region of the Ptet sequence upstream from mNG. Alternative plasmid constructs used as controls revealed a strong influence of transcription terminators and antibiotics resistance gene of the plasmid backbone on the resulting expression performance. In contrast to the TetR-Ptet-system, pBBR1MCS-5-based LacI-dependent expression from PlacUV5 always exhibited some non-induced basal reporter expression and was therefore tunable only up to 40-fold induction by IPTG. The leakiness of PlacUV5 when not induced was independent of potential read-through from the lacI promoter. Protein-DNA binding simulations for pH 7, 6, 5, and 4 by computational modeling of LacI, TetR, and AraC with DNA suggested a decreased DNA binding of LacI when pH is below 6, the latter possibly causing the leakiness of LacI-dependent systems hitherto tested in AAB. In summary, the expression performance of the pBBR1MCS-5-based TetR-Ptet system makes this system highly suitable for applications in G. oxydans and possibly in other AAB.
              
                Key Points
                • A pBBR1MCS-5-based TetR-Ptet system was tunable up to more than 3500-fold induction.
                • A pBBR1MCS-5-based LacI-PlacUV5 system was leaky and tunable only up to 40-fold.
                • Modeling of protein-DNA binding suggested decreased DNA binding of LacI at pH &lt; 6.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 447
TI  - Dissecting industrial fermentations of fine flavour cocoa through metagenomic analysis
JO  - Sci. Rep.
PY  - 2021
SP  - 8638
AU  - Fernández-Niño, M.
AU  - Rodríguez-Cubillos, M. J.
AU  - Herrera-Rocha, F.
AU  - Anzola, J. M.
AU  - Cepeda-Hernández, M. L.
AU  - Aguirre Mejía, J. L.
AU  - Chica, M. J.
AU  - Olarte, H. H.
AU  - Rodríguez-López, C.
AU  - Calderón, D.
AU  - Ramírez-Rojas, A.
AU  - Del Portillo, P.
AU  - Restrepo, S.
AU  - González Barrios, A. F.
AU  - 
VL  - 11
UR  - https://doi.org/10.1038/s41598-021-88048-3
DO  - 10.1038/s41598-021-88048-3
AB  - The global demand for fine-flavour cocoa has increased worldwide during the last years. Fine-flavour cocoa offers exceptional quality and unique fruity and floral flavour attributes of high demand by the world\'s elite chocolatiers. Several studies have highlighted the relevance of cocoa fermentation to produce such attributes. Nevertheless, little is known regarding the microbial interactions and biochemistry that lead to the production of these attributes on farms of industrial relevance, where traditional fermentation methods have been pre-standardized and scaled up. In this study, we have used metagenomic approaches to dissect on-farm industrial fermentations of fine-flavour cocoa. Our results revealed the presence of a shared core of nine dominant microorganisms (i.e. Limosilactobacillus fermentum, Saccharomyces cerevisiae, Pestalotiopsis rhododendri, Acetobacter aceti group, Bacillus subtilis group, Weissella ghanensis group, Lactobacillus_uc, Malassezia restricta and Malassezia globosa) between two farms located at completely different agro-ecological zones. Moreover, a community metabolic model was reconstructed and proposed as a tool to further elucidate the interactions among microorganisms and flavour biochemistry. Our work is the first to reveal a core of microorganisms shared among industrial farms, which is an essential step to process engineering aimed to design starter cultures, reducing fermentation times, and controlling the expression of undesirable phenotypes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 526
TI  - A single cytochrome P450 oxidase from Solanum habrochaites sequentially oxidizes 7-epi-zingiberene to derivatives toxic to whiteflies and various microorganisms
JO  - Plant J.
PY  - 2021
SP  - 1309-1325
AU  - Zabel, S.
AU  - Brandt, W.
AU  - Porzel, A.
AU  - Athmer, B.
AU  - Bennewitz, S.
AU  - Schäfer, P.
AU  - Kortbeek, R. W. J.
AU  - Bleeker, P. M.
AU  - Tissier, A.
AU  - 
VL  - 105
UR  - https://doi.org/10.1111/tpj.15113
DO  - 10.1111/tpj.15113
AB  - Secretions from glandular trichomes potentially protect plants against a variety of aggressors. In the tomato clade of the Solanum genus, glandular trichomes of wild species produce a rich source of chemical diversity at the leaf surface. Previously, 7-epi-zingiberene produced in several accessions of Solanum habrochaites was found to confer resistance to whiteflies (Bemisia tabaci) and other insect pests. Here, we report the identification and characterisation of 9-hydroxy-zingiberene (9HZ) and 9-hydroxy-10,11-epoxyzingiberene (9H10epoZ), two derivatives of 7-epi-zingiberene produced in glandular trichomes of S. habrochaites LA2167. Using a combination of transcriptomics and genetics, we identified a gene coding for a cytochrome P450 oxygenase, ShCYP71D184, that is highly expressed in trichomes and co-segregates with the presence of the zingiberene derivatives. Transient expression assays in Nicotiana benthamiana showed that ShCYP71D184 carries out two successive oxidations to generate 9HZ and 9H10epoZ. Bioactivity assays showed that 9-hydroxy-10,11-epoxyzingiberene in particular exhibits substantial toxicity against B. tabaci and various microorganisms including Phytophthora infestans and Botrytis cinerea. Our work shows that trichome secretions from wild tomato species can provide protection against a wide variety of organisms. In addition, the availability of the genes encoding the enzymes for the pathway of 7-epi-zingiberene derivatives makes it possible to introduce this trait in cultivated tomato by precision breeding.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 518
TI  - Dehydroquinate dehydratase/shikimate dehydrogenases involved in gallate biosynthesis of the aluminum-tolerant tree species Eucalyptus camaldulensis
JO  - Planta
PY  - 2021
SP  - 3
AU  - Tahara, K.
AU  - Nishiguchi, M.
AU  - Funke, E.
AU  - Miyazawa, S.-I.
AU  - Miyama, T.
AU  - Milkowski, C.
AU  - 
VL  - 253
UR  - https://link.springer.com/article/10.1007/s00425-020-03516-w#Sec31
DO  - 10.1007/s00425-020-03516-w
AB  - The tree species Eucalyptus camaldulensis shows exceptionally high tolerance against aluminum, a widespread toxic metal in acidic soils. In the roots of E. camaldulensis, aluminum is detoxified via the complexation with oenothein B, a hydrolyzable tannin. In our approach to elucidate the biosynthesis of oenothein B, we here report on the identification of E. camaldulensis enzymes that catalyze the formation of gallate, which is the phenolic constituent of hydrolyzable tannins. By systematical screening of E. camaldulensis dehydroquinate dehydratase/shikimate dehydrogenases (EcDQD/SDHs), we found two enzymes, EcDQD/SDH2 and 3, catalyzing the NADP+-dependent oxidation of 3-dehydroshikimate to produce gallate. Based on extensive in vitro assays using recombinant EcDQD/SDH2 and 3 enzymes, we present for the first time a detailed characterization of the enzymatic gallate formation activity, including the cofactor preferences, pH optima, and kinetic constants. Sequence analyses and structure modeling suggest the gallate formation activity of EcDQD/SDHs is based on the reorientation of 3-dehydroshikimate in the catalytic center, which facilitates the proton abstraction from the C5 position. Additionally, EcDQD/SDH2 and 3 maintain DQD and SDH activities, resulting in a 3-dehydroshikimate supply for gallate formation. In E. camaldulensis, EcDQD/SDH2 and 3 are co-expressed with UGT84A25a/b and UGT84A26a/b involved in hydrolyzable tannin biosynthesis. We further identified EcDQD/SDH1 as a “classical” bifunctional plant shikimate pathway enzyme and EcDQD/SDH4a/b as functional quinate dehydrogenases of the NAD+/NADH-dependent clade. Our data indicate that in E. camaldulensis the enzymes EcDQD/SDH2 and 3 provide the essential gallate for the biosynthesis of the aluminum-detoxifying metabolite oenothein B.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 517
TI  - Access to new cytotoxic triterpene and steroidal Acid-TEMPO Conjugates by ugi multicomponent-reactions
JO  - Int. J. Mol. Sci.
PY  - 2021
SP  - 7125
AU  - Sultani, H. N.
AU  - Morgan, I.
AU  - Hussain, H.
AU  - Roos, A. H.
AU  - Haeri, H. H.
AU  - Kaluđerović, G. N.
AU  - Hinderberger, D.
AU  - Westermann, B.
AU  - 
VL  - 22
UR  - https://doi.org/10.3390/ijms22137125
DO  - 10.3390/ijms22137125
AB  - Multicomponent reactions, especially the Ugi-four component reaction (U-4CR), provide powerful protocols to efficiently access compounds having potent biological and pharmacological effects. Thus, a diverse library of betulinic acid (BA), fusidic acid (FA), cholic acid (CA) conjugates with TEMPO (nitroxide) have been prepared using this approach, which also makes them applicable in electron paramagnetic resonance (EPR) spectroscopy. Moreover, convertible amide modified spin-labelled fusidic acid derivatives were selected for post-Ugi modification utilizing a wide range of reaction conditions which kept the paramagnetic center intact. The nitroxide labelled betulinic acid analogue 6 possesses cytotoxic effects towards two investigated cell lines: prostate cancer PC3 (IC50 7.4 ± 0.7 μM) and colon cancer HT29 (IC50 9.0 ± 0.4 μM). Notably, spin-labelled fusidic acid derivative 8 acts strongly against these two cancer cell lines (PC3: IC50 6.0 ± 1.1 μM; HT29: IC50 7.4 ± 0.6 μM). Additionally, another fusidic acid analogue 9 was also found to be active towards HT29 with IC50 7.0 ± 0.3 μM (CV). Studies on the mode of action revealed that compound 8 increased the level of caspase-3 significantly which clearly indicates induction of apoptosis by activation of the caspase pathway. Furthermore, the exclusive mitochondria targeting of compound 18 was successfully achieved, since mitochondria are the major source of ROS generation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 515
TI  - Transition from seeds to seedlings: Hormonal and epigenetic aspects
JO  - Plants
PY  - 2021
SP  - 1884
AU  - Smolikova, G.
AU  - Strygina, K.
AU  - Krylova, E.
AU  - Leonova, T.
AU  - Frolov, A.
AU  - Khlestkina, E.
AU  - Medvedev, S.
AU  - 
VL  - 10
UR  - https://doi.org/10.3390/plants10091884
DO  - 10.3390/plants10091884
AB  - Transition from seed to seedling is one of the critical developmental steps, dramatically affecting plant growth and viability. Before plants enter the vegetative phase of their ontogenesis, massive rearrangements of signaling pathways and switching of gene expression programs are required. This results in suppression of the genes controlling seed maturation and activation of those involved in regulation of vegetative growth. At the level of hormonal regulation, these events are controlled by the balance of abscisic acid and gibberellins, although ethylene, auxins, brassinosteroids, cytokinins, and jasmonates are also involved. The key players include the members of the LAFL network—the transcription factors LEAFY COTYLEDON1 and 2 (LEC 1 and 2), ABSCISIC ACID INSENSITIVE3 (ABI3), and FUSCA3 (FUS3), as well as DELAY OF GERMINATION1 (DOG1). They are the negative regulators of seed germination and need to be suppressed before seedling development can be initiated. This repressive signal is mediated by chromatin remodeling complexes—POLYCOMB REPRESSIVE COMPLEX 1 and 2 (PRC1 and PRC2), as well as PICKLE (PKL) and PICKLE-RELATED2 (PKR2) proteins. Finally, epigenetic methylation of cytosine residues in DNA, histone post-translational modifications, and post-transcriptional downregulation of seed maturation genes with miRNA are discussed. Here, we summarize recent updates in the study of hormonal and epigenetic switches involved in regulation of the transition from seed germination to the post-germination stage.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 514
TI  - Desiccation tolerance as the basis of long-term seed viability
JO  - Int. J. Mol. Sci.
PY  - 2021
SP  - 101
AU  - Smolikova, G.
AU  - Leonova, T.
AU  - Vashurina, N.
AU  - Frolov, A.
AU  - Medvedev, S.
AU  - 
VL  - 22
UR  - https://www.mdpi.com/1422-0067/22/1/101
DO  - 10.3390/ijms22010101
AB  - Desiccation tolerance appeared as the key adaptation feature of photoautotrophic organisms for survival in terrestrial habitats. During the further evolution, vascular plants developed complex anatomy structures and molecular mechanisms to maintain the hydrated state of cell environment and sustain dehydration. However, the role of the genes encoding the mechanisms behind this adaptive feature of terrestrial plants changed with their evolution. Thus, in higher vascular plants it is restricted to protection of spores, seeds and pollen from dehydration, whereas the mature vegetative stages became sensitive to desiccation. During maturation, orthodox seeds lose up to 95% of water and successfully enter dormancy. This feature allows seeds maintaining their viability even under strongly fluctuating environmental conditions. The mechanisms behind the desiccation tolerance are activated at the late seed maturation stage and are associated with the accumulation of late embryogenesis abundant (LEA) proteins, small heat shock proteins (sHSP), non-reducing oligosaccharides, and antioxidants of different chemical nature. The main regulators of maturation and desiccation tolerance are abscisic acid and protein DOG1, which control the network of transcription factors, represented by LEC1, LEC2, FUS3, ABI3, ABI5, AGL67, PLATZ1, PLATZ2. This network is complemented by epigenetic regulation of gene expression via methylation of DNA, post-translational modifications of histones and chromatin remodeling. These fine regulatory mechanisms allow orthodox seeds maintaining desiccation tolerance during the whole period of germination up to the stage of radicle protrusion. This time point, in which seeds lose desiccation tolerance, is critical for the whole process of seed development.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 513
TI  - In vitro antileishmanial and antischistosomal activities of anemonin isolated from the fresh leaves of Ranunculus multifidus Forsk
JO  - Molecules
PY  - 2021
SP  - 7473
AU  - Sirak, B.
AU  - Asres, K.
AU  - Hailu, A.
AU  - Dube, M.
AU  - Arnold, N.
AU  - Häberli, C.
AU  - Keiser, J.
AU  - Imming, P.
AU  - 
VL  - 26
UR  - https://doi.org/10.3390/molecules26247473
DO  - 10.3390/molecules26247473
AB  - Leishmaniasis and schistosomiasis are neglected tropical diseases (NTDs) infecting the world’s poorest populations. Effectiveness of the current antileishmanial and antischistosomal therapies are significantly declining, which calls for an urgent need of new effective and safe drugs. In Ethiopia fresh leaves of Ranunculus multifidus Forsk. are traditionally used for the treatment of various ailments including leishmaniasis and eradication of intestinal worms. In the current study, anemonin isolated from the fresh leaves of R. multifidus was assessed for its in vitro antileishmanial and antischistosomal activities. Anemonin was isolated from the hydro-distilled extract of the leaves of R. multifidus. Antileishmanial activity was assessed on clinical isolates of the promastigote and amastigote forms of Leishmania aethiopica and L. donovani clinical isolates. Resazurin reduction assay was used to determine antipromastigote activity, while macrophages were employed for antiamastigote and cytotoxicity assays. Antischistosomal assays were performed against adult Schistosoma mansoni and newly transformed schistosomules (NTS). Anemonin displayed significant antileishmanial activity with IC50 values of 1.33 nM and 1.58 nM against promastigotes and 1.24 nM and 1.91 nM against amastigotes of L. aethiopica and L. donovani, respectively. It also showed moderate activity against adult S. mansoni and NTS (49% activity against adult S. mansoni at 10 µM and 41% activity against NTS at 1 µM). The results obtained in this investigation indicate that anemonin has the potential to be used as a template for designing novel antileishmanial and antischistosomal pharmacophores.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 512
TI  - Expression and refolding of the plant chitinase from Drosera capensis for applications as a sustainable and integrated pest management
JO  - Front. Bioeng. Biotechnol.
PY  - 2021
SP  - 728501
AU  - Sinelnikov, I. G.
AU  - Siedhoff, N. E.
AU  - Chulkin, A. M.
AU  - Zorov, I. N.
AU  - Schwaneberg, U.
AU  - Davari, M. D.
AU  - Sinitsyna, O. A.
AU  - Shcherbakova, L. A.
AU  - Sinitsyn, A. P.
AU  - Rozhkova, A. M.
AU  - 
VL  - 9
UR  - https://doi.org/10.3389/fbioe.2021.728501
DO  - 10.3389/fbioe.2021.728501
AB  - Recently, the study of chitinases has become an important target of numerous research projects due to their potential for applications, such as biocontrol pest agents. Plant chitinases from carnivorous plants of the genus Drosera are most aggressive against a wide range of phytopathogens. However, low solubility or insolubility of the target protein hampered application of chitinases as biofungicides. To obtain plant chitinase from carnivorous plants of the genus Drosera in soluble form in E.coli expression strains, three different approaches including dialysis, rapid dilution, and refolding on Ni-NTA agarose to renaturation were tested. The developed « Rapid dilution » protocol with renaturation buffer supplemented by 10% glycerol and 2M arginine in combination with the redox pair of reduced/oxidized glutathione, increased the yield of active soluble protein to 9.5 mg per 1 g of wet biomass. A structure-based removal of free cysteines in the core domain based on homology modeling of the structure was carried out in order to improve the soluble of chitinase. One improved chitinase variant (C191A/C231S/C286T) was identified which shows improved expression and solubility in E. coli expression systems compared to wild type. Computational analyzes of the wild-type and the improved variant revealed overall higher fluctuations of the structure while maintaining a global protein stability. It was shown that free cysteines on the surface of the protein globule which are not involved in the formation of inner disulfide bonds contribute to the insolubility of chitinase from Drosera capensis. The functional characteristics showed that chitinase exhibits high activity against colloidal chitin (360 units/g) and high fungicidal properties of recombinant chitinases against Parastagonospora nodorum. Latter highlights the application of chitinase from D. capensis as a promising enzyme for the control of fungal pathogens in agriculture.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 510
TI  - Solvent mediated fabrication of ditched hollow indium sulfide (In2S3) spheres for overall electrocatalytic water splitting
JO  - Journal of The Electrochemical Society
PY  - 2021
SP  - 066510
AU  - Shamraiz, U.
AU  - Elizbit, .
AU  - Badshah, A.
AU  - Alfantazi, A.
AU  - Hussain, H.
AU  - Raza, B.
AU  - Ullah, S.
AU  - Green, I. R.
AU  - 
VL  - 168
UR  - https://doi.org/10.1149/1945-7111/ac0605
DO  - 10.1149/1945-7111/ac0605
AB  - The controlled synthesis of nanomaterials is of prime importance in modern-day science. We report the shape-controlled synthesis of In2S3 spheres via a one-step solvent-mediated method. The process is very economical as it only requires the switching of solvent during synthesis (pure ethylene glycol, ethylene glycol/water, and ethylene glycol/ethanol mixtures) to fabricate porous and hollow In2S3 spheres. We have deliberately chosen a high boiling solvent and a combination of high and low boiling solvents to control the morphology. The synthesized In2S3 hollow spheres proved to be electrocatalytically active for an overall electrocatalytic water splitting and drive the oxygen evolution reactions at 230 mV and the hydrogen evolution reactions at 239 mV to produce a current density of 10 mA cm-2, respectively.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 505
TI  - Metabolism of photosynthetic organisms
JO  - Life
PY  - 2021
SP  - 946
AU  - Savchenko, T.
AU  - Frolov, A.
AU  - 
VL  - 11
UR  - https://doi.org/10.3390/life11090946
DO  - 10.3390/life11090946
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 501
TI  - Total synthesis of Aetokthonotoxin, the cyanobacterial neurotoxin causing vacuolar myelinopathy
JO  - Chem.-Eur. J.
PY  - 2021
SP  - 12032-12035
AU  - Ricardo, M. G.
AU  - Schwark, M.
AU  - Llanes, D.
AU  - Niedermeyer, T. H. J.
AU  - Westermann, B.
AU  - 
VL  - 27
UR  - https://doi.org/10.1002/chem.202101848
DO  - 10.1002/chem.202101848
AB  - Aetokthonotoxin has recently been identified as the cyanobacterial neurotoxin causing Vacuolar Myelinopathy, a fatal neurologic disease, spreading through a trophic cascade and affecting birds of prey such as the bald eagle in the USA. Here, we describe the total synthesis of this specialized metabolite. The complex, highly brominated 1,2’-biindole could be synthesized via a Somei-type Michael reaction as key step. The optimised sequence yielded the natural product in five steps with an overall yield of 29 %.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 497
TI  - A modular two yeast species secretion system for the production and preparative application of unspecific peroxygenases
JO  - Commun. Biol.
PY  - 2021
SP  - 562
AU  - Püllmann, P.
AU  - Knorrscheidt, A.
AU  - Münch, J.
AU  - Palme, P. R.
AU  - Hoehenwarter, W.
AU  - Marillonnet, S.
AU  - Alcalde, M.
AU  - Westermann, B.
AU  - Weissenborn, M. J.
AU  - 
VL  - 4
UR  - https://www.nature.com/articles/s42003-021-02076-3
DO  - 10.1038/s42003-021-02076-3
AB  - AbstractFungal unspecific peroxygenases (UPOs) represent an enzyme class catalysing versatile oxyfunctionalisation reactions on a broad substrate scope. They are occurring as secreted, glycosylated proteins bearing a haem-thiolate active site and rely on hydrogen peroxide as the oxygen source. However, their heterologous production in a fast-growing organism suitable for high throughput screening has only succeeded once—enabled by an intensive directed evolution campaign. We developed and applied a modular Golden Gate-based secretion system, allowing the first production of four active UPOs in yeast, their one-step purification and application in an enantioselective conversion on a preparative scale. The Golden Gate setup was designed to be universally applicable and consists of the three module types: i) signal peptides for secretion, ii) UPO genes, and iii) protein tags for purification and split-GFP detection. The modular episomal system is suitable for use in Saccharomyces cerevisiae and was transferred to episomal and chromosomally integrated expression cassettes in Pichia pastoris. Shake flask productions in Pichia pastoris yielded up to 24 mg/L secreted UPO enzyme, which was employed for the preparative scale conversion of a phenethylamine derivative reaching 98.6 % ee. Our results demonstrate a rapid, modular yeast secretion workflow of UPOs yielding preparative scale enantioselective biotransformations.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 493
TI  - In Vitro Evaluation of Antiproliferative Properties of Novel Organotin(IV) Carboxylate Compounds with Propanoic Acid Derivatives on a Panel of Human Cancer Cell Lines
JO  - Molecules
PY  - 2021
SP  - 3199
AU  - Pantelić, N. ?.
AU  - Božić, B.
AU  - Zmejkovski, B. B.
AU  - Banjac, N. R.
AU  - Dojčinović, B.
AU  - Wessjohann, L. A.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 26
UR  - https://www.mdpi.com/1420-3049/26/11/3199
DO  - 10.3390/molecules26113199
AB  - The synthesis of novel triphenyltin(IV) compounds, Ph3SnLn (n = 1–3), with oxaprozin (3-(4,5-diphenyloxazol-2-yl)propanoic acid), HL1, and the new propanoic acid derivatives 3-(4,5-bis(4-methoxylphenyl)oxazol-2-yl)propanoic acid, HL2, and 3-(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)propanoic acid, HL3, has been performed. The ligands represent commercial drugs or their derivatives and the tin complexes have been characterized by standard analytical methods. The in vitro antiproliferative activity of both ligands and organotin(IV) compounds has been evaluated on the following tumour cell lines: human prostate cancer (PC-3), human colorectal adenocarcinoma (HT-29), breast cancer (MCF-7), and hepatocellular cancer (HepG2), as well as on normal mouse embryonic fibroblast cells (NIH3T3) with the aid of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystal violet) assays. Contrary to the inactive ligand precursors, all organotin(IV) carboxylates showed very good activity with IC50 values ranging from 0.100 to 0.758 µM. According to the CV assay (IC50 = 0.218 ± 0.025 µM), complex Ph3SnL1 demonstrated the highest cytotoxicity against the caspase 3 deficient MCF-7 cell line. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated a two-fold lower concentration of tin in MCF-7 cells in comparison to platinum. To investigate the mechanism of action of the compound Ph3SnL1 on MCF-7 cells, morphological, autophagy and cell cycle analysis, as well as the activation of caspase and ROS/RNS and NO production, has been performed. Results suggest that Ph3SnL1 induces caspase-independent apoptosis in MCF-7 cells.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 491
TI  - Anthelmintic and antimicrobial activities of three new depsides and ten known depsides and phenols from Indonesian lichen: Parmelia cetrata Ach.
JO  - Nat. Prod. Res.
PY  - 2021
SP  - 5001-5010
AU  - Nugraha, A. S.
AU  - Untari, L. F.
AU  - Laub, A.
AU  - Porzel, A.
AU  - Franke, K.
AU  - Wessjohann, L. A.
AU  - 
VL  - 35
UR  - https://doi.org/10.1080/14786419.2020.1761361
DO  - 10.1080/14786419.2020.1761361
AB  - An extensive phytochemical study of a foliose lichen from Indonesia, Parmelia cetrata, resulted in the successful isolation of 13 phenol and depside derivatives (1–13) including the previously unreported depsides 3′-hydroxyl-5′-pentylphenyl 2,4-dihydroxyl-6-methylbenzoate (7), 3′-hydroxyl-5′-propylphenyl 2,4-dihydroxyl-6-methylbenzoate (8) and 3′-hydroxyl-5′-methylphenyl 2-hydroxyl-4-methoxyl-6-propylbenzoate (9). The anti-infective activity of isolated compounds was evaluated against the gram-negative bacterium Aliivibrio fischeri and the nematode Caenorhabditis elegans. 2,4-Dihydroxyl-6-pentylbenzoate (5) and lecanoric acid (6) induced growth inhibition of A. fischeri with inhibition values of 49% and 100% at a concentration of 100 µM, respectively. The antibacterial activity might be due to their free carboxyl group. A phenolic group at C4 also contributed to the antimicrobial activity of the depsides as shown for compounds 7 and 8, which caused 89% and 96% growth inhibition at 100 µM, respectively. Lecanoric acid (6) in addition possesses significant anthelmintic effects causing 80% mortality of C. elegans at 100 µg/mL.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 528
TI  - A multifaceted review on dihydromyricetin resources, extraction, bioavailability, biotransformation, bioactivities, and food applications with future perspectives to maximize its value
JO  - eFood
PY  - 2021
SP  - 164-184
AU  - Zhang, H.
AU  - Caprioli, G.
AU  - Hussain, H.
AU  - Khoi Le, N. P.
AU  - Farag, M. A.
AU  - Xiao, J.
AU  - 
VL  - 2
UR  - https://doi.org/10.53365/efood.k/143518
DO  - 10.53365/efood.k/143518
AB  - Natural bioactive compounds present a better alternative to prevent and treat chronic diseases owing to their lower toxicity and abundant resources. (+)-Dihydromyricetin (DMY) is a flavanonol, possessing numerous interesting bioactivities with abundant resources. This review provides a comprehensive overview of the recent advances in DMY natural resources, stereoisomerism, physicochemical properties, extraction, biosynthesis, pharmacokinetics, and biotransformation. Stereoisomerism of DMY should be considered for better indication of its efficacy. Biotechnological approach presents a potential tool for the production of DMY using microbial cell factories. DMY high instability is related to its powerful antioxidant capacity due to pyrogallol moiety in ring B, and whether preparation of other analogues could demonstrate improved properties. DMY demonstrates poor bioavailability based on its low solubility and permeability with several attempts to improve its pharmacokinetics and efficacy. DMY possesses various pharmacological effects, which have been proven by many in vitro and in vivo experiments, while clinical trials are rather scarce, with underlying action mechanisms remaining unclear. Consequently, to maximize the usefulness of DMY in nutraceuticals, improvement in bioavailability, and better understanding of its actions mechanisms and drug interactions ought to be examined in the future along with more clinical evidence.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 530
TI  - Extraction and purification of cis/trans asarone from Acorus tatarinowii Schott: Accelerated solvent extraction and silver ion coordination high-speed counter-current chromatography
JO  - J. Chromatogr. A
PY  - 2021
SP  - 462080
AU  - Zhu, H.
AU  - Ali, I.
AU  - Hussain, H.
AU  - Hussain, M.
AU  - Wang, X.-B.
AU  - Song, X.
AU  - Luo, G.
AU  - Zhang, Z.
AU  - Wang, Z.
AU  - Wang, D.
AU  - 
VL  - 1643
UR  - https://doi.org/10.1016/j.chroma.2021.462080
DO  - 10.1016/j.chroma.2021.462080
AB  - Acorus tatarinowii Schott is a traditional Chinese medicine used to treat memory and cognitive dysfunction. Because of their efficacy and lower toxic effects, research on α- and β-asarone, the phytoconstituents, has attracted attention owing to their remarkable pharmacological activities. Silver ion coordination complexation high-speed counter-current chromatography was used to separate these isomers from A. tatarinowii extract, coupled with accelerated solvent extraction. Accelerated solvent extraction parameters were investigated with single-factor and orthogonal testing. A two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (2:1:2:1, v/v) with 0.50 mol/L silver ions was selected for separation. From 2.0 g crude extract, 1.4 g of β-asarone and 0.09 g of α-asarone were obtained with purities over 98% by sequential sample loading in 20 h. The isolated compounds were identified by electrospray ionization mass spectrometry, 1H and 13C NMR. Silver ions significantly increased the separation factor and retention of the stationary phase. The chromatographic behavior indicated that cis-configuration was more strongly complexed with the silver ion. This was further demonstrated with the help of computational analysis. In conclusion, the established method could be employed to separate other cis-trans or E/Z isomers that form coordination complexes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 529
TI  - Silver ion-complexation high-speed countercurrent chromatography coupled with prep-HPLC for separation of sesquiterpenoids from germacrene A fermentation broth
JO  - Fermentation
PY  - 2021
SP  - 230
AU  - Zhao, H.
AU  - Song, X.
AU  - Ali, I.
AU  - Hussain, M.
AU  - Mehmood, A.
AU  - Siyo, B.
AU  - Gao, Q.
AU  - Cui, L.
AU  - Aziz, S.
AU  - Hussain, H.
AU  - Ma, W.
AU  - Qin, D.
AU  - Wang, D.
AU  - 
VL  - 7
UR  - https://doi.org/10.3390/fermentation7040230
DO  - 10.3390/fermentation7040230
AB  - A silver ion high-speed counter-current chromatography ([Ag+]-HSCCC) was developed to separate and purify five sesquiterpenoids from germacrene A fermentation broth. The solvent system was consisted of n-hexane-methanol-silver nitrate (3 mol/L) solution (10:9.5:0.5, v/v). By employing this chromatographic protocol, five sesquiterpenoids named β-elemene (1; 54.1 mg), germacrene A (2; 28.5 mg), γ-selinene (3; 4.6 mg), β-selinene (4; 3.4 mg), and α-selinene (5; 1.3 mg) were obtained successfully from 500 mg extracted crude sample with purities of 97.1%, 95.2%, 98.2%, 96.3% and 98.5%, respectively, combined with preparative HPLC. The results reveal that the addition of metal ion in biphasic solvent system significantly improved the HSCCC separation factor of sesquiterpenoids. Meanwhile, our study also provided an alternate approach to separate the compounds with less polarity, also geometrical isomers and various natural product classes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 424
TI  - Anti-inflammatory potential of daturaolone from Datura innoxia Mill.: In silico, in vitro and in vivo studies
JO  - Pharmaceuticals
PY  - 2021
SP  - 1248
AU  - Baig, M. W.
AU  - Fatima, H.
AU  - Akhtar, N.
AU  - Hussain, H.
AU  - Okla, M. K.
AU  - Al-Hashimi, A.
AU  - Al-Qahtani, W. H.
AU  - AbdElgawad, H.
AU  - Haq, I.-u.
AU  - 
VL  - 14
UR  - https://doi.org/10.3390/ph14121248
DO  - 10.3390/ph14121248
AB  - Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood–brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC50) value in normal lymphocytes was &gt;20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC50 values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 422
TI  - Phyto-extract-mediated synthesis of silver nanoparticles using aqueous extract of Sanvitalia procumbens, and characterization, optimization and photocatalytic degradation of Azo Dyes Orange G and Direct Blue-15
JO  - Molecules
PY  - 2021
SP  - 6144
AU  - Aslam, M.
AU  - Fozia, F.
AU  - Gul, A.
AU  - Ahmad, I.
AU  - Ullah, R.
AU  - Bari, A.
AU  - Mothana, R. A.
AU  - Hussain, H.
AU  - 
VL  - 26
UR  - https://doi.org/10.3390/molecules26206144
DO  - 10.3390/molecules26206144
AB  - Green synthesis of silver nanoparticles (AgNPs) employing an aqueous plant extract has emerged as a viable eco-friendly method. The aim of the study was to synthesize AgNPs by using plant extract of Sanvitalia procumbens (creeping zinnia) in which the phytochemicals present in plant extract act as a stabilizing and reducing agent. For the stability of the synthesized AgNPs, different parameters like AgNO3 concentration, volume ratios of AgNO3, temperature, pH, and contact time were studied. Further, AgNPs were characterized by UV–visible spectroscopy, FT-IR (Fourier Transform Infrared Spectroscopy), XRD (X-ray Diffraction), SEM (Scanning Electron Microscopy), and EDX (Energy Dispersive X-ray Spectrometer) analysis. FT-IR analysis showed that the plant extract contained essential functional groups like O–H stretching of carboxylic acid, N–H stretching of secondary amides, and C–N stretching of aromatic amines, and C–O indicates the vibration of alcohol, ester, and carboxylic acid that facilitated in the green synthesis of AgNPs. The crystalline nature of synthesized AgNPs was confirmed by XRD, while the elemental composition of AgNPs was detected by energy dispersive X-ray analysis (EDX). SEM studies showed the mean particle diameter of silver nanoparticles. The synthesized AgNPs were used for photocatalytic degradation of Orange G and Direct blue-15 (OG and DB-15), which were analyzed by UV-visible spectroscopy. Maximum degradation percentage of OG and DB-15 azo dyes was observed, without any significant silver leaching, thereby signifying notable photocatalytic properties of AgNPs.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 420
TI  - Separation and anti-inflammatory evaluation of phytochemical constituents from Pleurospermum candollei (Apiaceae) by high-speed countercurrent chromatography with continuous sample load
JO  - J Sep Sci
PY  - 2021
SP  - 2663-2673
AU  - Ali, I.
AU  - Mu, Y.
AU  - Atif, M.
AU  - Hussain, H.
AU  - Li, J.
AU  - Li, D.
AU  - Shabbir, M.
AU  - Bankeu, J. J. K.
AU  - Cui, L.
AU  - Sajjad, S.
AU  - Wang, D.
AU  - Wang, X.
AU  - 
VL  - 44
UR  - https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/jssc.202100155
DO  - 10.1002/jssc.202100155
AB  - Pleurospermum (Apiaceae) species possess a wide range of biological properties viz. analgesic, anti-inflammatory, antimalarial, and so on. Pleurospermum candollei (DC.) Benth. Ex C. B. Clark. is reported to cure diarrhea, gastric, respiratory, stomach, abdominal, joint, and back pain problems. In addition, it is also used for both male and female infertility. The present study deals with an efficient technique using high-speed countercurrent chromatography for separation of chemical components from the methanol extract of P. candollei. Notably, nine main compounds namely luteolin 7-O-glucoside (1), oxypeucedanin hydrate (2), pabulenol (3), bergapten (4), heptadecanoic acid (5), (E)-isoelemicin (6), trans-asarone (7), α-linolenic acid (8), and isoimperatorin (9) were very efficiently separated and isolated in pure form. Multiple injections were applied followed by two off-line recycling high-speed countercurrent chromatography. The inhibitory effect of nitric oxide production of all compounds was tested in the presence of 200 ng/mL lipopolysaccharide in RAW264.7 mice macrophage cells. The results demonstrated that compounds 7 and 8 effectively inhibited nitric oxide production, with IC50 values of 28.44 and 53.18 μM, respectively. This study thus validates the traditional claim of using P. candollei. Taken together, these findings will be useful in future research to find a potential candidate with anti-inflammatory properties.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 419
TI  - Phytochemical analysis and biological activities of “Cherchoomoro” (Nepeta adenophyta Hedge)
JO  - J. Ethnopharmacol.
PY  - 2021
SP  - 114402
AU  - Ali, I.
AU  - Ali, M.
AU  - Shareef, H.
AU  - Naeem, S.
AU  - Khadim, A.
AU  - Ali, M.
AU  - Amber, F.
AU  - Hussain, H.
AU  - Ismail, M.
AU  - Shah, S. T. A.
AU  - Noor, A.
AU  - Wang, D.
AU  - 
VL  - 279
UR  - https://doi.org/10.1016/j.jep.2021.114402
DO  - 10.1016/j.jep.2021.114402
AB  - Ethnopharmacological relevance: Nepeta adenophyta Hedge (Lamiaceae) is an endemic therapeutic herb from Astore, Gilgit (Pakistan). This plant species has been reported among the local communities, especially for treating abdominal pain, kidney pain, menstrual pain, headache, and controlling bleeding disorders. Therefore, the scientific basis is provided for the relief of pain as it is used in various pain management among the natives, especially as ethnogynecological herbal remedy.
Aim of the study: The present study investigates the analgesic and anti-inflammatory effects of the ethanolic extract of N. adenophyta in animal models. Furthermore, the extract was also studied to determine their valuable phytoconstituents.
Material and methods: The biological effects were determined via tail-flick, hot plate, and acetic-acid-induced abdominal writhing methods. At the same time, anti-inflammatory activity was assesed via oxidative burst and antioxidant DPPH assay. Gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS) techniques were employed to understand the phytochemicals present in the crude ethanolic extract of Nepeta adenophyta.
Results: In the current study, Nepeta adenophyta extract exhibited potent analgesic and anti-inflammatory effects on different pain models and indicated that the analgesic effect of N. adenophyta extract is mediated both in central and peripheral ways. Dose-dependent and significant (P &lt; 0.05) increases were shown in pain threshold, at 45 min post-treatment, with 20 and 40 mg/kg of the extract in the tail-flick model. The effects of the extract were similar to aspirin but lower to those by morphine (2.5 mg/kg) in the same tests. The extract (20–40 mg/kg) showed dose-dependent inhibition of writhing with a significant (P &lt; 0.001) increase protection against thermal stimuli in hot plate test as compared to control and similar to aspirin and morphine. Further, the anti-inflammatory activity of the crude in oxidative burst and DPPH assays showed significant inhibitory activity. The chemical profile analysis showed major phytochemicals, including long chain derivatives of alkane and alcohol, phenolics, naphthalene, naphthopyran, androsten phenanthrenone, nepetalactones, flavonoids etc.
Conclusions: Nepeta adenophyta Hedge is suggested as a natural alternative for mild pain relief. Our findings endorse the folklore use of N. adenophyta in different pain managements which can be attributed to the presence of polyphenolic compounds, naphthalene derivatives, flavanoids and nepetalactones etc.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 418
TI  - Hepatoprotective screening of Seriphidium kurramense (Qazilb.) Y.R. Ling
JO  - BioMed Research International
PY  - 2021
SP  - 9026731
AU  - Ali, M.
AU  - Hussain, H.
AU  - Hussain, A.
AU  - Rauf, A.
AU  - Hussain, W.
AU  - Ullah, M.
AU  - Abbas, S.
AU  - Al-Awthan, Y. S.
AU  - Bahattab, O.
AU  - Khan, M.
AU  - Olatunde, A.
AU  - Almarhoon, Z. M.
AU  - Mabkhot, Y. N.
AU  - Alshehri, M. M.
AU  - Daştan, S. D.
AU  - Ramadan, M. F.
AU  - Sharifi-Rad, J.
AU  - 
VL  - 2021
UR  - https://doi.org/10.1155/2021/9026731
DO  - 10.1155/2021/9026731
AB  - Investigation on medicinal plants’ therapeutic potential has gained substantial importance in the discovery of novel effective and safe therapeutic agents. The present study is aimed at investigating the hepatoprotective potential of Seriphidium kurramense methanolic extract (SKM) against carbon tetrachloride- (CCl4-) induced hepatotoxicity in rats. S. kurramense is one of the most imperative plants for its various pharmacological activities. Therefore, this study was aimed at evaluating the hepatoprotective potential against CCl4-induced liver toxicity. The serum samples were analyzed for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) together with the oxidative stress mediator levels as nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), reduced glutathione (GSH), and superoxide dismutase (SOD) as well as peroxidation and H2O2 activity. CCl4 administration resulted in an elevated free radical generation, altered liver marker (AST and ALT) enzymes, reduced antioxidant enzyme, and increased DNA damage. Methanolic extract of S. kurramense decreased CCl4-induced hepatotoxicity by increasing the antioxidant status and reducing H2O2 and nitrate content generation as well as reducing DNA damage. Additionally, SKM reversed the morphological alterations induced by CCl4 in the SKM-treated groups. These results demonstrated that SKM displayed hepatoprotective activity against CCl4-induced hepatic damage in experimental rats.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 417
TI  - Sugar containing compounds and biological activities of Lagochilus setulosus
JO  - Molecules
PY  - 2021
SP  - 1755
AU  - Akramov, D. K.
AU  - Mamadalieva, N. Z.
AU  - Porzel, A.
AU  - Hussain, H.
AU  - Dube, M.
AU  - Akhmedov, A.
AU  - Altyar, A. E.
AU  - Ashour, M. L.
AU  - Wessjohann, L. A.
AU  - 
VL  - 26
UR  - https://www.mdpi.com/1420-3049/26/6/1755
DO  - 10.3390/molecules26061755
AB  - Phytochemical investigation of the methanolic extract obtained from the aerial parts of Lagochilus setulosus (Lamiaceae) afforded the new compound 1-methoxy-3-O-β-glucopyranosyl-α-l-oliose (1) together with five known glycosides, namely sitosterol-3-O-β-glucoside (2), stigmasterol-3-O-β-glucoside (3), pinitol (4), 6β-hydroxyl-7-epi-loganin (5), and chlorotuberoside (6). The structures of these compounds were elucidated by extensive spectroscopic analyses, especially HR-MS, 1D and 2D NMR spectroscopy. The in vitro cytotoxic activity of the methanolic extract and the isolated compounds was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and crystal violet (CV) staining assays. In addition, the antifungal activities of the components were evaluated against Botrytis cinerea, Septoria tritici, and Phytophthora infestans. The anthelmintic potential was determined against Caenorhabditis elegans nematodes. Neither the extract nor the isolated compounds showed promising activity in all the bioassays.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 415
TI  - Structural characterization of plant glucosylceramides and thecorresponding ceramides by UHPLC-LTQ-Orbitrap mass spectrometry
JO  - J. Pharm. Biomed. Anal.
PY  - 2021
SP  - 113677
AU  - Adem, A. A.
AU  - Belete, A.
AU  - Soboleva, A.
AU  - Frolov, A.
AU  - Tessema, E. N.
AU  - Gebre-Mariam, T.
AU  - Neubert, R. H.
AU  - 
VL  - 192
UR  - https://doi.org/10.1016/j.jpba.2020.113677
DO  - 10.1016/j.jpba.2020.113677
AB  - Ceramides (CERs) play a major role in skin barrier function and direct replacement of depleted skin CERs,due to skin disorder or aging, has beneficial effects in improving skin barrier function and skin hydration.Though, plants are reliable source of CERs, absence of economical and effective method of hydrolysis toconvert the dominant plant sphingolipid, glucosylceramides (GlcCERs), into CERs remains a challenge.This study aims at exploring alternative GlcCERs sources and chemical method of hydrolysis into CERsfor dermal application. GlcCERs isolated from lupin bean (Lupinus albus), mung bean (Vigna radiate) andnaked barley (Hordium vulgare) were identified using ultra high performance liquid chromatographyhyphenated with atmospheric pressure chemical ionization - high resolution tandem mass spectrometer(UHPLC/APCI-HRMS/MS) and quantified with validated automated multiple development-high perfor-mance thin layer chromatography (AMD-HPTLC) method. Plant GlcCERs were hydrolyzed into CERs withmild acid hydrolysis (0.1 N HCl) after treating them with oxidizing agent, NaIO4,and reducing agent,NaBH4. GlcCERs with 4,8-sphingadienine, 8-sphingenine and 4-hydroxy-8-sphingenine sphingoid baseslinked with C14 to C26  -hydroxylated fatty acids (FAs) were identified. Single GlcCER (m/z 714.5520)was dominant in lupin and mung beans while five major GlcCERs species (m/z 714.5520, m/z 742.5829,m/z 770.6144, m/z 842.6719 and m/z 844.56875) were obtained from naked barley. The GlcCERs con-tents of the three plants were comparable. However, lupin bean contains predominantly (&gt; 98 %) a singleGlcCER (m/z 714.5520). Considering the affordability, GlcCER content and yield, lupin bean would bethe preferred alternative commercial source of GlcCERs. CER species bearing 4,8-sphingadienine and 8-sphingenine sphingoid bases attached to C14 to 24 FAs were found after mild acid hydrolysis. CER specieswith m/z 552.4992 was the main component in the beans while CER with m/z 608.5613 was dominantin the naked barley. However, CERs with 4-hydroxy-8-sphingenine sphingoid base were not detected inUHPLC-HRMS/MS study suggesting that the method works for mainly GlcCERs carrying dihydroxy sph-ingoid bases. The method is economical and effective which potentiates the commercialization of plantCERs for dermal application.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 446
TI  - Downy mildew resistance is genetically mediated by prophylactic production of phenylpropanoids in hop
JO  - Plant Cell Environ.
PY  - 2021
SP  - 323-338
AU  - Feiner, A.
AU  - Pitra, N.
AU  - Matthews, P.
AU  - Pillen, K.
AU  - Wessjohann, L. A.
AU  - Riewe, D.
AU  - 
VL  - 44
UR  - https://onlinelibrary.wiley.com/doi/10.1111/pce.13906
DO  - 10.1111/pce.13906
AB  - Downy mildew in hop (Humulus lupulus L.) is caused by Pseudoperonospora humuli and generates significant losses in quality and yield. To identify the biochemical processes that confer natural downy mildew resistance (DMR), a metabolome- and genomewide association study was performed. Inoculation of a high density genotyped F1 hop population (n = 192) with the obligate biotrophic oomycete P. humuli led to variation in both the levels of thousands of specialized metabolites and DMR. We observed that metabolites of almost all major phytochemical classes were induced 48 hr after inoculation. But only a small number of metabolites were found to be correlated with DMR and these were enriched with phenylpropanoids. These metabolites were also correlated with DMR when measured from the non-infected control set. A genome-wide association study revealed co-localization of the major DMR loci and the phenylpropanoid pathway markers indicating that the major contribution to resistance is mediated by these metabolites in a heritable manner. The application of three putative prophylactic phenylpropanoids led to a reduced degree of leaf infection in susceptible genotypes, confirming their protective activity either directly or as precursors of active compounds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 445
TI  - UPLC-MS Metabolome-Based Seed Classification of 16 Vicia Species: A Prospect for Phyto-Equivalency and Chemotaxonomy of Different Accessions
JO  - J. Agr. Food Chem.
PY  - 2021
SP  - 5252-5266
AU  - Fayek, N. M.
AU  - Mekky, R. H.
AU  - Dias, C. N.
AU  - Kropf, M.
AU  - Heiss, A. G.
AU  - Wessjohann, L. A.
AU  - Farag, M. A.
AU  - 
VL  - 69
UR  - 
DO  - 10.1021/acs.jafc.0c06054
AB  - Seeds of domesticated Vicia (vetch) species (family Fabaceae-Faboideae) 
are produced and consumed worldwide for their nutritional value. Seed 
accessions belonging to 16 different species of Vicia—both domesticated 
and wild taxa—were subjected to a chemotaxonomic study using 
ultraperformance liquid chromatography–mass spectrometry (UPLC-MS) 
analyzed by chemometrics. A total of 89 metabolites were observed in the
 examined Vicia accessions. Seventy-eight out of the 89 detected 
metabolites were annotated. Metabolites quantified belonged to several 
classes, viz., flavonoids, procyanidins, prodelphinidins, anthocyanins, 
stilbenes, dihydrochalcones, phenolic acids, coumarins, alkaloids, 
jasmonates, fatty acids, terpenoids, and cyanogenics, with flavonoids 
and fatty acids amounting to the major classes. Flavonoids, fatty acids,
 and anthocyanins showed up as potential chemotaxonomic markers in Vicia
 species discrimination. Fatty acids were more enriched in Vicia faba specimens, while the abundance of flavonoids was the highest in Vicia parviflora. Anthocyanins allowed for discrimination between Vicia hirsuta and Vicia sepium.
 To the best of our knowledge, this is the first report on employing 
UPLC-MS metabolomics to discern the diversity of metabolites at the 
intrageneric level among Vicia species.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 444
TI  - Unraveling the metabolome composition and its implication for Salvadora persica L. use as dental brush via a multiplex approach of NMR and LC–MS metabolomics
JO  - J. Pharm. Biomed. Anal.
PY  - 2021
SP  - 113727
AU  - Farag, M. A.
AU  - Shakour, Z. T.
AU  - Lübken, T.
AU  - Frolov, A.
AU  - Wessjohann, L. A.
AU  - Mahrous, E.
AU  - 
VL  - 193
UR  - https://doi.org/10.1016/j.jpba.2020.113727
DO  - 10.1016/j.jpba.2020.113727
AB  - Salvadora persica L. (toothbrush tree, Miswak) is well recognized in most Middle Eastern and African countries for its potential role in dental care, albeit the underlying mechanism for its effectiveness is still not fully understood. A comparative MS and NMR metabolomics approach was employed to investigate the major primary and secondary metabolites composition of S. persica in context of its organ type viz., root or stem to rationalize for its use as a tooth brush. NMR metabolomics revealed its enrichment in nitrogenous compounds including proline-betaines i.e., 4-hydroxy-stachydrine and stachydrine reported for the first time in S. persica. LC/MS metabolomics identified flavonoids (8), benzylurea derivatives (5), butanediamides (3), phenolic acids (8) and 5 sulfur compounds, with 21 constituents reported for the first time in S. persica. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) of either NMR or LC/MS dataset clearly separated stem from root specimens based on nitrogenous compounds abundance in roots and is justifying for its preference as toothbrush versus stems. The presence of betaines at high levels in S. persica (9−12 μg/mg dry weight) offers novel insights into its functioning as an osmoprotectant that maintains the hydration of oral mucosa. Additionally, the previously described anti-inflammatory activity of stachydrine along with the antimicrobial effects of sulfonated flavonoids, benzylisothiocynate and ellagic acid derivatives are likely contributors to S. persica oral hygiene health benefits. Among root samples, variation in sugars and organic acids levels were the main discriminatory criterion. This study provides the first standardization of S. persica extract using qNMR for further inclusion in nutraceuticals.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 443
TI  - Nuclear magnetic resonance metabolomics approach for the analysis of major legume sprouts coupled to chemometrics
JO  - Molecules
PY  - 2021
SP  - 761
AU  - Farag, M. A.
AU  - Sharaf El-Din, M. G.
AU  - Selim, M. A.
AU  - Owis, A. I.
AU  - Abouzid, S. F.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - Otify, A.
AU  - 
VL  - 26
UR  - https://www.mdpi.com/1420-3049/26/3/761
DO  - 10.3390/molecules26030761
AB  - Legume sprouts are a fresh nutritive source of phytochemicals of increasing attention worldwide owing to their many health benefits. Nuclear magnetic resonance (NMR) was utilized for the metabolite fingerprinting of 4 major legume sprouts, belonging to family Fabaceae, to be exploited for quality control purposes. Thirty-two metabolites were identified belonging to different classes, i.e., fatty acids, sugars, amino acids, nucleobases, organic acids, sterols, alkaloids, and isoflavonoids. Quantitative NMR was employed for assessing the major identified metabolite levels and multivariate data analysis was utilized to assess metabolome heterogeneity among sprout samples. Isoflavones were detected exclusively in Cicer sprouts, whereas Trigonella was characterized by 4-hydroxyisoleucine. Vicia sprouts were distinguished from other legume sprouts by the presence of L-Dopa versus acetate abundance in Lens. A common alkaloid in all sprouts was trigonelline, detected at 8–25 µg/mg, suggesting its potential role in legume seeds’ germination. Trigonelline was found at highest levels in Trigonella sprouts. The aromatic NMR region data (δ 11.0–5.0 ppm) provided a better classification power than the full range (δ 11.0–0.0 ppm) as sprout variations mostly originated from secondary metabolites, which can serve as chemotaxonomic markers.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 441
TI  - Anthelmintic activity and cytotoxic effects of compounds isolated from the fruits of Ozoroa insignis Del. (Anacardiaceae)
JO  - Biomolecules
PY  - 2021
SP  - 1893
AU  - Dube, M.
AU  - Saoud, M.
AU  - Rennert, R.
AU  - Fotso, G. W.
AU  - Andrae-Marobela, K.
AU  - Imming, P.
AU  - Häberli, C.
AU  - Keiser, J.
AU  - Arnold, N.
AU  - 
VL  - 11
UR  - https://doi.org/10.3390/biom11121893
DO  - 10.3390/biom11121893
AB  - Ozoroa insignis Del. is an ethnobotanical plant widely used in traditional medicine for various ailments, including schistosomiasis, tapeworm, and hookworm infections. From the so far not investigated fruits of Ozoroa insignis, the anthelmintic principles could be isolated through bioassay-guided isolation using Caenorhabditis elegans and identified by NMR spectroscopic analysis and mass spectrometric studies. Isolated 6-[8(Z)-pentadecenyl] anacardic (1), 6-[10(Z)-heptadecenyl] anacardic acid (2), and 3-[7(Z)-pentadecenyl] phenol (3) were evaluated against the 5 parasitic organisms Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum, which mainly infect humans and other mammals. Compounds 1–3 showed good activity against Schistosoma mansoni, with compound 1 showing the best activity against newly transformed schistosomula with 50% activity at 1µM. The isolated compounds were also evaluated for their cytotoxic properties against PC-3 (human prostate adenocarcinoma) and HT-29 (human colorectal adenocarcinoma) cell lines, whereby compounds 2 and 3 showed antiproliferative activity in both cancer cell lines, while compound 1 exhibited antiproliferative activity only on PC-3 cells. With an IC50 value of 43.2 µM, compound 3 was found to be the most active of the 3 investigated compounds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 440
TI  - Antitumor potential of cisplatin loaded into SBA-15 mesoporous silica nanoparticles against B16F1 melanoma cells: in vitro and in vivo studies
JO  - J. Inorg. Biochem.
PY  - 2021
SP  - 111383
AU  - Drača, D.
AU  - Edeler, D.
AU  - Saoud, M.
AU  - Dojčinović, B.
AU  - Dunđerović, D.
AU  - Đmura, G.
AU  - Maksimović-Ivanić, D.
AU  - Mijatović, S.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 217
UR  - https://doi.org/10.1016/j.jinorgbio.2021.111383
DO  - 10.1016/j.jinorgbio.2021.111383
AB  - CP (cisplatin) and mesoporous silica SBA-15 (Santa Barbara amorphous 15) loaded with CP (→SBA-15&#124;CP) were tested in vitro and in vivo against low metastatic mouse melanoma B16F1 cell line. SBA-15 only, as drug carrier, is found to be not active, while CP and SBA-15&#124;CP revealed high cytotoxicity in lower μM range. The activity of SBA-15&#124;CP was found similar to the activity of CP alone. Both CP and SBA-15&#124;CP induced inhibition of cell proliferation (carboxyfluorescein succinimidyl ester - CFSE assay) along with G2/M arrest (4′,6-diamidino-2-phenylindole - DAPI assay). Apoptosis (Annexin V/ propidium iodide - PI assay), through caspase activation (apostat assay) and nitric oxide (NO) production (diacetate(4-amino-5-methylamino-2′,7′-difluorofluorescein-diacetat) - DAF FM assay), was identified as main mode of cell death. However, slight elevated autophagy (acridine orange - AO assay) was detected in treated B16F1 cells. CP and SBA-15&#124;CP did not affect production of ROS (reactive oxygen species) in B16F1 cells. Both SBA-15&#124;CP and CP induced in B16F1 G2 arrest and subsequent senescence. SBA-15&#124;CP, but not CP, blocked the growth of melanoma in C57BL/6 mice. Moreover, hepato- and nephrotoxicity in SBA-15&#124;CP treated animals were diminished in comparison to CP confirming multiply improved antitumor potential of immobilized CP. Outstandingly, SBA-15 boosted in vivo activity and diminished side effects of CP.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 438
TI  - Synthesis and biological evaluation of highly potent fungicidal deoxy‐hygrophorones
JO  - Eur. J. Org. Chem.
PY  - 2021
SP  - 3827-3836
AU  - Ditfe, T.
AU  - Bette, E.
AU  - N. Sultani, H.
AU  - Otto, A.
AU  - Wessjohann, L. A.
AU  - Arnold, N.
AU  - Westermann, B.
AU  - 
VL  - 2021
UR  - https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/ejoc.202100729
DO  - 10.1002/ejoc.202100729
AB  - Although stripped from hydroxyl-groups, deoxygenated
 hygrophorones remain highly active against severe phytopathogens. The 
synthesis to these natural product congeners is achieved in 
rearrangement sequences, with an optimized deprotection strategy 
avoiding retro-aldol reactions. The activities are comparable to 
fungicides used in agriculture.
            
               
            Based on naturally occurring hygrophorones, racemic di- 
and mono-hydroxylated cyclopentenones bearing an aliphatic side chain 
have been produced in short synthetic sequences starting from furfuryl 
aldehyde. For the series of dihydroxylated trans-configured derivatives, an Achmatowicz-rearrangement and a Caddick-ring contraction were employed, and for the series of trans-configured
 mono-hydroxylated derivatives a Piancatelli-rearrangement. All final 
products showed good to excellent fungicidal activities against the 
plant pathogens B. cinerea, S. tritici and P. infestans.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 437
TI  - Role of ABCA7 in human health and in alzheimer’s disease
JO  - Int. J. Mol. Sci.
PY  - 2021
SP  - 4603
AU  - Dib, S.
AU  - Pahnke, J.
AU  - Gosselet, F.
AU  - 
VL  - 22
UR  - https://doi.org/10.3390/ijms22094603
DO  - 10.3390/ijms22094603
AB  - Several studies, including genome wide association studies (GWAS), have strongly suggested a central role for the ATP-binding cassette transporter subfamily A member 7 (ABCA7) in Alzheimer’s disease (AD). This ABC transporter is now considered as an important genetic determinant for late onset Alzheimer disease (LOAD) by regulating several molecular processes such as cholesterol metabolism and amyloid processing and clearance. In this review we shed light on these new functions and their cross-talk, explaining its implication in brain functioning, and therefore in AD onset and development.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 436
TI  - UHPLC-ESI-Orbitrap-HR-MS analysis of cyclopeptide alkaloids from Ziziphus joazeiro
JO  - Nat. Prod. Commun.
PY  - 2021
SP  - 1-13
AU  - Corrêa dos Santos, C. H.
AU  - Geraldo de Carvalho, M.
AU  - Laub, A.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - 
VL  - 16
UR  - https://doi.org/10.1177/1934578X211054955
DO  - 10.1177/1934578x211054955
AB  - Ziziphus joazeiro Mart., popularly known as “juazeiro”, is a tree widely found in the northeast of Brazil. It is commonly used as an anti-inflammatory, antibacterial, antifungal, and analgesic agent. The stem extract exhibited, beside cytotoxic properties, substantial activity against the Gram-negative bacterium Allivibrio fischeri. UHPLC-ESI-Orbitrap-HR-MS analysis of the alkaloidal fraction of the crude methanolic stem extract of this species enabled the detection and putative identification of sixteen cyclopeptide alkaloids (CPAs), including four possibly new structures. According to the MS2 fragmentation analysis, from the sixteen identified CPAs, three possess a type-Ia1, one a type-Ia2, and twelve a type-Ib cyclopeptide alkaloid core. The structures of paliurine-C and -D were supported by NMR data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 434
TI  - Efficient enzyme-catalyzed production of diosgenin: inspired by the biotransformation mechanisms of steroid saponins in Talaromyces stollii CLY-6
JO  - Green Chemistry
PY  - 2021
SP  - 5896-5910
AU  - Cheng, L.
AU  - Zhang, H.
AU  - Cui, H.
AU  - Davari, M. D.
AU  - Wei, B.
AU  - Wang, W.
AU  - Yuan, Q.
AU  - 
VL  - 23
UR  - https://doi.org/10.1039/D0GC04152A
DO  - 10.1039/d0gc04152a
AB  - Diosgenin is an important raw material of numerous synthetic steroidal drugs, such as sex hormones, contraceptives, and cortisone. Diosgenin production by enzymatic catalysis provides a solution for avoiding severe environmental issues caused by conventional acid hydrolysis. However, exploring high-efficiency enzymes and setting up catalytic processes still remain challenging. Herein, we identified a strain named Talaromyces stollii CLY-6, which showed efficient transformation of steroid saponins into diosgenin. Through genomic analysis and protein fingerprinting, two novel steroid saponin glycosidases (Rhase-TS: α-L-rhamnosidase; Gluase-TS: β-D-glucosidase) were discovered from Talaromyces stollii CLY-6. Enzyme over-expression and functional investigation suggested that Rhase-TS is capable of specifically hydrolyzing the terminal α-L-1,2-rhamnoside of steroid saponins, and Gluase-TS can release the residual glucose groups, thereby revealing a microbial transformation mechanism of steroid saponins and providing an enzymatic foundation for guiding diosgenin production. Notably, Rhase-TS exhibited excellent enzymatic properties with high thermostability (&lt;70 °C), broad pH stability (pH 3.0 to 10.0), high rhamnose tolerance (Ki: 0.5 M), and high catalytic activity (136.34 U mg−1). Inspired by the above studies, a whole-enzyme-catalyzed approach was explored and optimized to efficiently prepare diosgenin at the gram-level (up to 96.5% yield). Compared with conventional acid hydrolysis, this enzyme-based approach showed a significant advantage in reducing environmental pollution and increasing economic benefits, offering a promising alternative for green and eco-friendly diosgenin production.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 432
TI  - Structural modeling of two plant UDP-dependent sugar-sugar glycosyltransferases reveals a conserved glutamic acid residue that is a hallmark for sugar acceptor recognition
JO  - Journal of Structural Biology
PY  - 2021
SP  - 107777
AU  - Brandt, W.
AU  - Schulze, E.
AU  - Liberman-Aloni, R.
AU  - Bartelt, R.
AU  - Pienkny, S.
AU  - Carmeli-Weissberg, M.
AU  - Frydman, A.
AU  - Eyal, Y.
AU  - 
VL  - 213
UR  - https://doi.org/10.1016/j.jsb.2021.107777
DO  - 10.1016/j.jsb.2021.107777
AB  - Glycosylation is one of the common modifications of plant metabolites, playing a major role in the chemical/biological diversity of a wide range of compounds. Plant metabolite glycosylation is catalyzed almost exclusively by glycosyltransferases, mainly by Uridine-diphosphate dependent Glycosyltransferases (UGTs). Several X-ray structures have been determined for primary glycosyltransferases, however, little is known regarding structure–function aspects of sugar-sugar/branch-forming O-linked UGTs (SBGTs) that catalyze the transfer of a sugar from the UDP-sugar donor to an acceptor sugar moiety of a previously glycosylated metabolite substrate.In this study we developed novel insights into the structural basis for SBGT catalytic activity by modelling the 3d-structures of two enzymes; a rhamnosyl-transferase Cs1,6RhaT – that catalyzes rhamnosylation of flavonoid-3-glucosides and flavonoid-7-glucosides and a UGT94D1 – that catalyzes glucosylation of (+)-Sesaminol 2-O-β-Dglucoside at the C6 of the primary sugar moiety.Based on these structural models and docking studies a glutamate (E290 or E268 in Cs1,6RhaT or UGT94D1, respectively) and a tryptophan (W28 or W15 in Cs1,6RhaT or UGT94D1, respectively) appear to interact with the sugar acceptor and are suggested to be important for the recognition of the sugar-moiety of the acceptorsubstrate.Functional analysis of substitution mutants for the glutamate and tryptophan residues in Cs1,6RhaT further support their role in determining sugar-sugar/branch-forming GT specificity.Phylogenetic analysis of the UGT family in plants demonstrates that the glutamic-acid residue is a hallmark of SBGTs that is entirely absent from the corresponding position in primary UGTs.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 429
TI  - Diversity and host relationships of the mycoparasite Sepedonium (Hypocreales, Ascomycota) in temperate central Chile
JO  - Microorganisms
PY  - 2021
SP  - 2261
AU  - Binimelis-Salazar, J.
AU  - CASANOVA-KATNY, A.
AU  - Arnold, N.
AU  - Lima, C. A.
AU  - Norambuena, H. V.
AU  - González-Rocha, G.
AU  - Palfner, G.
AU  - 
VL  - 9
UR  - https://doi.org/10.3390/microorganisms9112261
DO  - 10.3390/microorganisms9112261
AB  - We present the first major survey of regional diversity, distribution and host-association of Sepedonium. Whereas the rather scarce worldwide records of this mycoparasitic fungus suggested no specific distribution pattern of most species before, we provide new evidence of endemic and specific host-parasite guilds of Sepedonium in Southern South America, including the description of a new species. The corresponding inventory was performed in temperate central Chile. The regional landscape, a mosaic of exotic timber plantations and remnants of native Nothofagus forests, facilitates a unique combination of endemic and adventitious Boletales hosts. During a two-year survey, 35 Sepedonium strains were isolated and cultured from infected basidiomata of allochthonous Chalciporus piperatus, Paxillus involutus, Rhizopogon spp. and Suillus spp., as well as from the native Boletus loyita, B. loyo, B. putidus and Gastroboletus valdivianus. Taxonomic diagnosis included morphology of conidia and conidiophores, sequences of ITS, RPB2 and EF1 molecular markers and characteristics of in vitro cultures. Phylogenetic reconstructions were performed using Bayesian methods. Four Sepedonium species could be identified and characterized, viz.: S. ampullosporum, S. chrysospermum, S. laevigatum and the newly described species S. loyorum. The most frequent species on introduced Boletales was S. ampullosporum, followed by S. chrysospermum and S. laevigatum. S. loyorum sp. nov. was found exclusively on native boletacean hosts, separated from its closest relative S. chalcipori by micromorphological and molecular attributes. Species descriptions and identification keys are provided. Ecological and biogeographical aspects of endemic and allochthonous symbiotic units consisting of mycoparasite, ectomycorrhizal fungal host and respective mycorrhizal tree are discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 428
TI  - New derivatives of 11-keto-β-boswellic acid (KBA) induce apoptosis in breast and prostate cancers cells
JO  - Nat. Prod. Res.
PY  - 2021
SP  - 707-716
AU  - Bini Araba, A.
AU  - Ur Rehman, N.
AU  - Al-Araimi, A.
AU  - Al-Hashmi, S.
AU  - Al-Shidhani, S.
AU  - Csuk, R.
AU  - Hussain, H.
AU  - Al-Harrasi, A.
AU  - Zadjali, F.
AU  - 
VL  - 35
UR  - https://doi.org/10.1080/14786419.2019.1593165
DO  - 10.1080/14786419.2019.1593165
AB  - A series of new 11-keto-β-boswellic acid were partially-synthesized by modifying the hydroxyl and carboxylic acid functional groups of ring A. The structures of the new analogs were confirmed by detailed spectral data analysis. Compounds 4, 5 and 9 exhibited potent anti-cancer results against two human tumor cancer cell lines having IC50 value of MCF-7 (breast) and LNCaP (prostate): 123.6, 9.6 and 88.94 μM and 9.6, 44.12 and 12.03 μM, respectively. Additionally, a maximum nuclear fragmentation was observed for 4 (78.44%) in AKBA treated cells after 24 hr followed by 5 and 9 with (74.25 and 66.9% respectively). This study suggests that the presence of hydrazone functionality (4 and 9) has effectively improved the potency of AKBA. Interestingly, compound 5 with a lost carboxylic acid group of ring A showed comparable potent activity. Highly selective AKBA requires further modification to improve its bioavailability and solubility inside the cancer cells.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 427
TI  - Implication and evaluations of indoor soot particles from domestic fuel energy sources using characterization techniques in northern Pakistan
JO  - Microsc. Res. Tech.
PY  - 2021
SP  - 3161-3170
AU  - Bibi, S. D.
AU  - Baig, S. A.
AU  - Zeb, I.
AU  - Ali, M.
AU  - Shams, D. F.
AU  - Nawab, J.
AU  - Yosifova Aneva, I.
AU  - Hussain, H.
AU  - Xu, X.
AU  - 
VL  - 84
UR  - https://doi.org/10.1002/jemt.23873
DO  - 10.1002/jemt.23873
AB  - Soot particles emitted from the burning of solid fuel sources in the households carry important environmental and public health implications. In this study, the indoor soot particles released from firewood, cow dung, and bagasse burning at households of selected rural areas of Khyber Pakhtunkhwa province of Pakistan were investigated by characterization analyses to study its morphological and elemental compositions. Results demonstrated diverse compositions of soot particles from each fuel source. The surface areas of soot particles emitted by the firewood, cow dung, and bagasse were about 0.3, 0.4, and 8.64 m2 g−1, respectively. For the soot particles emitted by the firewood burning, the major functional groups for aromatic compounds were C═C at the 1,431–1,599 at 1,000–2,000 cm−1. The absorbance rate of alkanes was about 1,599–1,431 at 1,000–2,000 cm−1. However, silicon band vibration was more prominent in bagasse soot particles as compared to other samples. The emission of soot particles with high surface area in the atmosphere could provide an elevated adsorption sites for atmospheric pollution and trap more energy resulting in increased atmospheric temperature. Findings from the present study suggest that current households\' fuel combustion practices significantly contribute to increase the particulate matter in the atmosphere and possible enhance climate change phenomenon and related disasters in northern Pakistan.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 426
TI  - Machine learning-supported analyses improve quantitative histological assessments of amyloid-β deposits and activated Microglia
JO  - J. Alzheimers Dis.
PY  - 2021
SP  - 597-605
AU  - Bascuñana, P.
AU  - Brackhan, M.
AU  - Pahnke, J.
AU  - 
VL  - 79
UR  - https://content.iospress.com/articles/journal-of-alzheimers-disease/jad201120
DO  - 10.3233/JAD-201120
AB  - Background: Detailed pathology analysis and morphological quantification is tedious and prone to errors. Automatic image analysis can help to increase objectivity and reduce time. Here, we present the evaluation of the DeePathology STUDIO™
for automatic analysis of histological whole-slide images using machine learning/artificial intelligence.
Objective: To evaluate and validate the use of DeePathology STUDIO for the analysis of histological slides at high resolution.
Methods: We compared the DeePathology STUDIO and our current standard method using macros in AxioVision for the analysis of amyloid-β (Aβ) plaques and microglia in APP-transgenic mice at different ages. We analyzed density variables and total time invested with each approach. In addition, we correlated Aβ concentration in brain tissue measured by ELISA with the results of Aβ staining analysis.
Results: DeePathology STUDIO showed a significant decrease of the time for establishing new analyses and the total analysis time by up to 90%. On the other hand, both approaches showed similar quantitative results in plaque and activated microglia density in the different experimental groups. DeePathology STUDIO showed higher sensitivity and accuracy for small-sized plaques. In addition, DeePathology STUDIO allowed the classification of plaques in diffuse- and dense-packed, which was not possible with our traditional analysis.
Conclusion: DeePathology STUDIO substantially reduced the effort needed for a new analysis showing comparable quantitative results to the traditional approach. In addition, it allowed including different objects (categories) or cell types in a single analysis, which is not possible with conventional methods.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 12
TI  - Individual glycation sites as biomarkers of Type 2 diabetes mellitus
T2  - Type 2 Diabetes from Pathophysiology to Cyber Systems
PB  - IntechOpen
PY  - 2021
SP  - 
AU  - Soboleva, A.
AU  - Vashurina, N.
AU  - Frolov, A.
AU  - 
VL  - 
UR  - http://dx.doi.org/10.5772/intechopen.95532
SN  - 978-1-83881-903-3
DO  - 10.5772/intechopen.95532
AB  - Type 2 diabetes mellitus (T2DM) is a widely spread metabolic disease, the initial stages of which are asymptomatic and have no clinically recognizable manifestation. At the molecular level, T2DM is manifested with essential non-enzymatic structural changes of intra- and extracellular proteins, mostly represented with oxidation and glycation of multiple residues. Protein glycation is one of the most universal markers of T2DM, and is recognized as an indirect, but adequate indicator of plasma glucose levels over prolonged periods of time. Unfortunately, glycated hemoglobin (HbA1c) – the universally accepted T2DM marker, is insensitive for short-term excursions of blood glucose, which are known to precede the onset of disease. Therefore, new generation biomarkers, giving access to the time dimension of Maillard reaction in blood, are desired. In this context, establishment of individual glycation sites of plasma proteins as new T2DM biomarkers might be a promising approach. Indeed, involvement of proteins with different half-life times in such analysis will make the time dimension of protein glycation in blood available and will allow early recognition of blood sugar fluctuations, occurring within few weeks or even days.
A2  - Dr. Anca Pantea Stoian
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 11
TI  - Multi-Omics data mining: A novel tool for BioBrick design
T2  - Synthetic Genomics - From BioBricks to Synthetic Genomes [Working Title]
PB  - IntechOpen
PY  - 2021
SP  - 
AU  - Burgos-Toro, A.
AU  - Dippe, M.
AU  - Vásquez, A. F.
AU  - Pierschel, E.
AU  - Wessjohann, L. A.
AU  - Fernández-Niño, M.
AU  - 
VL  - 
UR  - http://dx.doi.org/10.5772/intechopen.101351
DO  - 10.5772/intechopen.101351
AB  - Currently, billions of nucleotide and amino acid sequences accumulate in free-access databases as a result of the omics revolution, the improvement in sequencing technologies, and the systematic storage of shotgun sequencing data from a large and diverse number of organisms. In this chapter, multi-omics data mining approaches will be discussed as a novel tool for the identification and characterization of novel DNA sequences encoding elementary parts of complex biological systems (BioBricks) using omics libraries. Multi-omics data mining opens up the possibility to identify novel unknown sequences from free-access databases. It also provides an excellent platform for the identification and design of novel BioBricks by using previously well-characterized biological bricks as scaffolds for homology searching and BioBrick design. In this chapter, the most recent mining approaches will be discussed, and several examples will be presented to highlight its relevance as a novel tool for synthetic biology.
A2  - Iva Ribic
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2523
TI  - Two novel 7-epi-zingiberene derivatives with biological activity from Solanum habrochaites are produced by a single cytochrome P450 monooxygenase
JO  - bioRxiv
PY  - 2020
SP  - 
AU  - Zabel, S.
AU  - Brandt, W.
AU  - Porzel, A.
AU  - Athmer, B.
AU  - Kortbeek, R. W. J.
AU  - Bleeker, P. M.
AU  - Tissier, A.
AU  - 
VL  - 
UR  - 
DO  - 10.1101/2020.04.21.052571
AB  - Secretions from glandular trichomes potentially protect the plant against a variety of aggressors. In the tomato genus, wild species constitute a rich source of chemical diversity produced at the leaf surface by glandular trichomes. Previously, 7-epi-zingiberene produced in several accessions of Solanum habrochaites was found to confer resistance to whiteflies (Bemisia tabaci) and other insect pests. Here, we identify two derivatives of 7-epi-zingiberene from S. habrochaites that had not been reported as yet. We identified them as 9-hydroxy-zingiberene and 9-hydroxy-10,11-epoxyzingiberene. Using a combination of genetics and transcriptomics we identified a single cytochrome P450 oxygenase, ShCYP71D184 that carries out two successive oxidations to generate the two sesquiterpenoids. Bioactivity assays showed that only 9-hydroxy-10,11-epoxyzingiberene exhibits substantial toxicity against B. tabaci. In addition, both 9-hydroxy-zingiberene and 9-hydroxy-10,11-epoxyzingiberene display substantial growth inhibitory activities against a range of microorganisms, including Bacillus subtilis, Phytophtora infestans and Botrytis cinerea. Our work shows that trichome secretions from wild tomato species can provide protection against a wide variety of organisms. In addition, the availability of the genes encoding the enzymes for the pathway of 7-epi-zingiberene derivatives makes it possible to introduce this trait in cultivated tomato by precision breeding.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2519
TI  - A modular two yeast species secretion system for the production and preparative application of fungal peroxygenases
JO  - bioRxiv
PY  - 2020
SP  - 
AU  - Püllmann, P.
AU  - Knorrscheidt, A.
AU  - Münch, J.
AU  - Palme, P. R.
AU  - Hoehenwarter, W.
AU  - Marillonnet, S.
AU  - Alcalde, M.
AU  - Westermann, B.
AU  - Weissenborn, M. J.
AU  - 
VL  - 
UR  - 
DO  - 10.1101/2020.07.22.216432
AB  - Fungal unspecific peroxygenases (UPOs) are biocatalysts of outstanding interest. Providing access to novel UPOs using a modular secretion system was the central goal of this work. UPOs represent an enzyme class, catalysing versatile oxyfunctionalisation reactions on a broad substrate scope. They are occurring as secreted, glycosylated proteins bearing a haem-thiolate active site and solely rely on hydrogen peroxide as the oxygen source. Fungal peroxygenases are widespread throughout the fungal kingdom and hence a huge variety of UPO gene sequences is available. However, the heterologous production of UPOs in a fast-growing organism suitable for high throughput screening has only succeeded once—enabled by an intensive directed evolution campaign. Here, we developed and applied a modular Golden Gate-based secretion system, allowing the first yeast production of four active UPOs, their one-step purification and application in an enantioselective conversion on a preparative scale. The Golden Gate setup was designed to be broadly applicable and consists of the three module types: i) a signal peptide panel guiding secretion, ii) UPO genes, and iii) protein tags for purification and split-GFP detection. We show that optimal signal peptides could be selected for successful UPO secretion by combinatorial testing of 17 signal peptides for each UPO gene. The modular episomal system is suitable for use in Saccharomyces cerevisiae and was transferred to episomal and chromosomally integrated expression cassettes in Pichia pastoris. Shake flask productions in Pichia pastoris yielded up to 24 mg/L secreted UPO enzyme, which was employed for the preparative scale conversion of a phenethylamine derivative reaching 98.6 % ee. Our results demonstrate a rapid workflow from putative UPO gene to preparative scale enantioselective biotransformations.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - DATA
ID  - 2506
TI  - PSYCHE - a valuable experiment in plant NMR-metabolomics
JO  - RADAR
PY  - 2020
SP  - 
AU  - Stark, P.
AU  - Zab, C.
AU  - Porzel, A.
AU  - Franke, K.
AU  - Rizzo, P.
AU  - Wessjohann, L. A.
AU  - 
VL  - 
UR  - https://www.radar-service.eu/radar/en/dataset/nUwWpwHaWREjQglm
DO  - 10.22000/338
AB  - Dataset: NMR raw dataInstrument: Agilent VNMRS 600 NMR spectrometer
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 580
TI  - Hypericibacter terrae gen. nov., sp. nov. and Hypericibacter adhaerens sp. nov., two new members of the family Rhodospirillaceae isolated from the rhizosphere of Hypericum perforatum
JO  - Int. J. Syst. Evol. Microbiol.
PY  - 2020
SP  - 1850-1860
AU  - Noviana, Z.
AU  - Vieira, S.
AU  - Pascual, J.
AU  - Fobofou, S. A. T.
AU  - Rohde, M.
AU  - Spröer, C.
AU  - Bunk, B.
AU  - Overmann, J.
AU  - 
VL  - 70
UR  - 
DO  - 10.1099/ijsem.0.003983
AB  - Two strains of the family Rhodospirillaceae were isolated from the rhizosphere of the medicinal plant Hypericum perforatum. Cells of both strains were Gram-stain-negative, motile by means of a single polar flagellum, non-spore-forming, non-capsulated, short rods that divided by binary fission. Colonies were small and white. Strains R5913T and R5959T were oxidase-positive, mesophilic, neutrophilic and grew optimally without NaCl. Both grew under aerobic and microaerophilic conditions and on a limited range of substrates with best results on yeast extract. Major fatty acids were C19 : 0 cyclo ω8c and C16 : 0; in addition, C18 : 1ω7c was also found as a predominant fatty acid in strain R5913T. The major respiratory quinone was ubiquinone 10 (Q-10). The DNA G+C contents of strains R5913T and R5959T were 66.0 and 67.4 mol%, respectively. 16S rRNA gene sequence comparison revealed that the closest relatives (&lt;92 % similarity) of the strains are Oceanibaculum pacificum MCCC 1A02656T, Dongia mobilis CGMCC 1.7660T, Dongia soli D78T and Dongia rigui 04SU4-PT. The two novel strains shared 98.6 % sequence similarity and represent different species on the basis of low average nucleotide identity of their genomes (83.8 %). Based on the combined phenotypic, genomic and phylogenetic investigations, the two strains represent two novel species of a new genus in the family Rhodospirillaceae , for which the name Hypericibacter gen. nov. is proposed, comprising the type species Hypericibacter terrae sp. nov. (type strain R5913T=DSM 109816T=CECT 9472T) and Hypericibacter adhaerens sp. nov. (type strain R5959T=DSM 109817T=CECT 9620T).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 577
TI  - Predicting the substrate scope of the flavin‐dependent halogenase BrvH
JO  - ChemBioChem
PY  - 2020
SP  - 3282–3288
AU  - Neubauer, P. R.
AU  - Pienkny, S.
AU  - Wessjohann, L. A.
AU  - Wessjohann, L.
AU  - Brandt, W.
AU  - Sewald, N.
AU  - 
VL  - 21
UR  - https://doi.org/10.1002/cbic.202000444
DO  - 10.1002/cbic.202000444
AB  - The recently described flavin‐dependent halogenase BrvH is able to catalyze both bromination and chlorination of indole, but shows significantly higher bromination activity. BrvH was annotated as a tryptophan halogenase, but does not accept tryptophan as a substrate. Its native substrate remains unknown. A predictive model with the data available for BrvH was analysed. A training set of compounds tested in vitro was docked into the active site of a complete protein model based on the X‐ray structure of BrvH. The atoms not resolved experimentally have been modelled using molecular mechanics force fields to obtain this protein model. Furthermore, docking poses for the substrates and known non‐substrates have been calculated. Parameters like distance, partial charge, and hybridization state have been analysed to derive rules for prediction of activity. With this model for activity of the BrvH, a virtual screening suggested several structures for potential substrates. Some of the thus preselected compounds were tested in vitro and several could be verified as convertible substrates. Based on information on halogenated natural products, a new dataset was created to specifically search for natural products as substrates/products, and virtual screening in this database yielded further hits.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 576
TI  - Direct Delivery of Health Promoting β-Asp-Arg Dipeptides via Stable Co-expression of Cyanophycin and the Cyanophycinase CphE241 in Tobacco Plants
JO  - Front. Plant Sci.
PY  - 2020
SP  - 842
AU  - Nausch, H.
AU  - Dorn, M.
AU  - Frolov, A.
AU  - Hoedtke, S.
AU  - Wolf, P.
AU  - Broer, I.
AU  - 
VL  - 11
UR  - 
DO  - 10.3389/fpls.2020.00842
AB  - Feed supplementation with β-arginine-aspartate dipeptides (β-Asp-Arg DP) shows growth promoting effects in feeding trials with fish and might also be beneficial for pig and poultry farming. Currently, these DPs are generated from purified cyanophycin (CGP), with the help of the CGP-degrading enzyme cyanophycinase (CGPase). As alternative to an in vitro production, the DPs might be directly produced in feed crops. We already demonstrated that CGP can be produced in plastids of tobacco and potato, yielding up to 9.4% of the dry weight (DW). We also transiently co-expressed CGPases in the cytosol without degrading CGP in intact cells, while degradation occurs in the homogenized plant tissue. However, transient co-expression is not feasible for field-grown CGP plants, which is necessary for bulk production. In the present study, we proved that stable co-expression of the CGPase CphE241 in CGP-producing tobacco is sufficient to degrade 2.0% CGP/DW nearly completely within 3 h after homogenization of the leaves. In intact senescing leaves, CGP is partially released to the cytosol and degraded into DPs which limits the overall accumulation of CGP but not the level of the stable DPs. Even after 48 h, 54 μmol β-Asp-Arg DP/g DW could be detected in the extract, which correspond to 1.5% DP/DW and represents 84% of the expected amount. Thus, we developed a system for the production of β-Asp-Arg DP in field-grown plants.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 575
TI  - Using a qPCR device to screen for modulators of ABC transporter activity: A step-by-step protocol
JO  - J. Pharmacol. Toxicol. Methods
PY  - 2020
SP  - 106882
AU  - Möhle, L.
AU  - Schwarzová, B.
AU  - Krohn, M.
AU  - Stefan, S. M.
AU  - Pahnke, J.
AU  - 
VL  - 104
UR  - 
DO  - 10.1016/j.vascn.2020.106882
AB  - IntroductionAdenosine triphosphate (ATP)-binding cassette (ABC) transporters are transmembrane proteins which actively transport a large variety of substrates across biological membranes. ABC transporter overexpression can be the underlying cause of multidrug resistance in oncology. Moreover, it has been revealed that increased ABCC1 transporter activity can ameliorate behavioural changes and Aβ pathology in a rodent model of Alzheimer&#39;s disease and it is currently tested in AD patients.MethodsFinding substances that modulate ABC transporter activity (inhibitors and activators) is of high relevance and thus, different methods have been developed to screen for potential modulators. For this purpose, we have developed a cell-based assay to measure the kinetics of ABCC1-mediated efflux of a fluorescent dye using a common qPCR device (Agilent AriaMx).ResultsWe validated the specificity of our method with vanadate and benzbromarone controls. Furthermore, we provide a step-by-step protocol including statistical analysis of the resulting data and suggestions how to modify the protocol specifically to screen for activators of ABCC1.DiscussionOur approach is biologically more relevant than cell-free assays. The continuous detection of kinetics allows for a more precise quantification compared with assays with single end-point measurements.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 574
TI  - Rewarding compounds identified from the medicinal plant Rhodiola rosea
JO  - J. Exp. Biol.
PY  - 2020
SP  - jeb223982
AU  - Michels, B.
AU  - Franke, K.
AU  - Weiglein, A.
AU  - Sultani, H.
AU  - Gerber, B.
AU  - Wessjohann, L. A.
AU  - 
VL  - 223
UR  - https://doi.org/10.1242/jeb.223982
DO  - 10.1242/jeb.223982
AB  - Preparations of Rhodiola rosea root are widely used in traditional medicine. They can increase life span in worms and flies, and have various effects related to nervous system function in different animal species and humans. However, which of the compounds in R. rosea is mediating any one of these effects has remained unknown in most cases. Here, an analysis of the volatile and non-volatile low-molecular-weight constituents of R. rosea root samples was accompanied by an investigation of their behavioral impact on Drosophila melanogaster larvae. Rhodiola rosea root samples have an attractive smell and taste to the larvae, and exert a rewarding effect. This rewarding effect was also observed for R. rosea root extracts, and did not require activity of dopamine neurons that mediate known rewards such as sugar. Based on the chemical profiles of R. rosea root extracts and resultant fractions, a bioactivity-correlation analysis (AcorA) was performed to identify candidate rewarding compounds. This suggested positive correlations for – among related compounds – ferulic acid eicosyl ester (FAE-20) and β-sitosterol glucoside. A validation using these as pure compounds confirmed that the correlations were causal. Their rewarding effects can be observed even at low micromolar concentrations and thus at remarkably lower doses than for any known taste reward in the larva. We discuss whether similar rewarding effects, should they be observed in humans, would indicate a habit-forming or addictive potential.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 573
TI  - SpCas9- and LbCas12a-Mediated DNA Editing Produce Different Gene Knockout Outcomes in Zebrafish Embryos
JO  - Genes
PY  - 2020
SP  - 740
AU  - Meshalkina, D. A.
AU  - Glushchenko, A. S.
AU  - Kysil, E. V.
AU  - Mizgirev, I. V.
AU  - Frolov, A.
AU  - 
VL  - 11
UR  - 
DO  - 10.3390/genes11070740
AB  - CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein) genome editing is a powerful technology widely used in current genetic research. In the most simple and straightforward way it can be applied for a gene knockout resulting from repair errors, induced by dsDNA cleavage by Cas nuclease. For decades, zebrafish (Danio rerio) has been known as a convenient model object of developmental biology. Both commonly used nucleases SpCas9 (Streptococcus pyogenes Cas9) and LbCas12a (Lachnospiraceae bacterium Cas12a) are extensively used in this model. Among them, LbCas12a is featured with higher specificity and efficiency of homology-directed editing in human cells and mouse. But the editing outcomes for these two nucleases in zebrafish are still not compared quantitatively. Therefore, to reveal possible advantages of one nuclease in comparison to the other in the context of gene knockout generation, we compare here the outcomes of repair of the DNA breaks introduced by these two commonly used nucleases in zebrafish embryos. To address this question, we microinjected the ribonucleoprotein complexes of the both nucleases with the corresponding guide RNAs in zebrafish zygotes and sequenced the target gene regions after three days of development. We found that LbCas12a editing resulted in longer deletions and more rare inserts, in comparison to those generated by SpCas9, while the editing efficiencies (percentage of mutated copies of the target gene to all gene copies in the embryo) of both nucleases were the same. On the other hand, overlapping of protospacers resulted in similarities in repair outcome, although they were cut by two different nucleases. Thus, our results indicate that the repair outcome depends both on the nuclease mode of action and on protospacer sequence.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 572
TI  - Isonitriles: Versatile handles for the bioorthogonal functionalization of proteins
JO  - ACS Omega
PY  - 2020
SP  - 25505-25510
AU  - Méndez, Y.
AU  - Vasco, A. V.
AU  - Humpierre, A. R.
AU  - Westermann, B.
AU  - 
VL  - 5
UR  - 
DO  - 10.1021/acsomega.0c03728
AB  - The property of the isonitrile group to enable the simultaneous α-addition of a strong electrophile and a nucleophile has always attracted the attention of organic chemists. Its versatility is augmented when recognizing that its high structural compactness, the inertia to most of the naturally occurring functional groups, and relatively prolonged physiological and metabolical stability, convert it into the smallest bioorthogonal group. The discovery and optimization of the isonitrile-tetrazine [4+1] cycloaddition as an alternative tool for the development of ligation and decaging strategies and the recently reported reaction of isonitriles with chlorooximes bring new opportunities for the utilization of this functional group in biological systems. Although several approaches have been reported for the synthesis of isonitrile-modified carbohydrates and polysaccharides, its incorporation in proteins has been barely explored. Besides compiling the reported methods for the assembly of isonitrile-modified proteins, this Mini-Review aims at calling attention to the real potential of this modification for protein ligation, decaging, immobilization, imaging, and many other applications at a low structural and functional cost.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 570
TI  - Recent advances in genus
            Mentha
            : Phytochemistry, antimicrobial effects, and food applications
JO  - Food Frontiers
PY  - 2020
SP  - 435-458
AU  - Mamadalieva, N. Z.
AU  - Hussain, H.
AU  - Xiao, J.
AU  - 
VL  - 1
UR  - https://onlinelibrary.wiley.com/doi/full/10.1002/fft2.53
DO  - 10.1002/fft2.53
AB  - The genus Mentha (mint) belongs to the Lamiaceae family, which 
includes 25 to 30 species. The species of this genus have been known for their medicinal and aromatherapeutic properties since ancient times and possess a significant economical and commercial reputation. Several 
species of Mentha are widely used in culinary and traditional medicines in many parts of the world. Essential oils from Mentha
 species have been commonly used as flavoring substance in beverages, 
providing a “fresh-like” aroma and taste. Chemical analyses of Mentha species have yielded a number of important phytocompounds belonging to different classes, such as organic acids, flavonoids, sterols, alkaloids, lignans, hydrocarbons, fatty acids, tocopherols, proteins, free sugars, etc. Moreover, the main compounds in mints are essential oils, phenolics, and flavonoids. This review reports the available information on the present status (literature up to early 2020) of the Mentha species and summarizes the chemical constituents, traditional and culinary uses, cultivation, and biological properties. In addition, comprehensive analysis of the antibacterial studies conducted on Mentha species is represented. In effect, Mentha species have been presented here as a viable alternative source of many biological and chemically active compounds which are already known to be of great economic, pharmaceutical, and nutritional importance.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 569
TI  - Natural and Semisynthetic Chalcones as Dual FLT3 and Microtubule Polymerization Inhibitors
JO  - J. Nat. Prod.
PY  - 2020
SP  - 3111-3121
AU  - Malik, H. S.
AU  - Bilal, A.
AU  - Ullah, R.
AU  - Iqbal, M.
AU  - Khan, S.
AU  - Ahmed, I.
AU  - Krohn, K.
AU  - Saleem, R. S. Z.
AU  - Hussain, H.
AU  - Faisal, A.
AU  - 
VL  - 83
UR  - 
DO  - 10.1021/acs.jnatprod.0c00699
AB  - Activating mutations in FLT3 receptor tyrosine kinase are found in a third of acute myeloid leukemia (AML) patients and are associated with disease relapse and a poor prognosis. The majority of these mutations are internal tandem duplications (ITDs) in the juxtamembrane domain of FLT3, which have been validated as a therapeutic target. The clinical success of selective inhibitors targeting oncogenic FLT3, however, has been limited due to the acquisition of drug resistance. Herein the identification of a dual FLT3/microtubule polymerization inhibitor, chalcone 4 (2′-allyloxy-4,4′-dimethoxychalcone), is reported through screening of 15 related chalcones for differential antiproliferative activity in leukemia cell lines dependent on FLT3-ITD (MV-4-11) or BCR-ABL (K562) oncogenes and by subsequent screening for mitotic inducers in the HCT116 cell line. Three natural chalcones (1–3) were found to be differentially more potent toward the MV-4-11 (FLT3-ITD) cell line compared to the K562 (BCR-ABL) cell line. Notably, the new semisynthetic chalcone 4, which is a 2′-O-allyl analogue of the natural chalcone 3, was found to be more potent toward the FLT3-ITD+ cell line and inhibited FLT3 signaling in FLT3-dependent cells. An in vitro kinase assay confirmed that chalcone 4 directly inhibited FLT3. Moreover, chalcone 4 induced mitotic arrest in these cells and inhibited tubulin polymerization in both cellular and biochemical assays. Treatment of MV-4-11 cells with this inhibitor for 24 and 48 h resulted in apoptotic cell death. Finally, chalcone 4 was able to overcome TKD mutation-mediated acquired resistance to FLT3 inhibitors in a MOLM-13 cell line expressing FLT3-ITD with the D835Y mutation. Chalcone 4 is, therefore, a promising lead for the discovery of dual-target FLT3 inhibitors.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 568
TI  - Does Protein Glycation Impact on the Drought-Related Changes in Metabolism and Nutritional Properties of Mature Pea (Pisum sativum L.) Seeds?
JO  - Int. J. Mol. Sci.
PY  - 2020
SP  - 567
AU  - Leonova, T.
AU  - Popova, V.
AU  - Tsarev, A.
AU  - Henning, C.
AU  - Antonova, K.
AU  - Rogovskaya, N.
AU  - Vikhnina, M.
AU  - Baldensperger, T.
AU  - Soboleva, A.
AU  - Dinastia, E.
AU  - Dorn, M.
AU  - Shiroglasova, O.
AU  - Grishina, T.
AU  - Balcke, G. U.
AU  - Ihling, C.
AU  - Smolikova, G.
AU  - Medvedev, S.
AU  - Zhukov, V. A.
AU  - Babakov, V.
AU  - Tikhonovich, I. A.
AU  - Glomb, M. A.
AU  - Bilova, T.
AU  - Frolov, A.
AU  - 
VL  - 21
UR  - 
DO  - 10.3390/ijms21020567
AB  - Protein glycation is usually referred to as an array of non-enzymatic post-translational modifications formed by reducing sugars and carbonyl products of their degradation. The resulting advanced glycation end products (AGEs) represent a heterogeneous group of covalent adducts, known for their pro-inflammatory effects in mammals, and impacting on pathogenesis of metabolic diseases and ageing. In plants, AGEs are the markers of tissue ageing and response to environmental stressors, the most prominent of which is drought. Although water deficit enhances protein glycation in leaves, its effect on seed glycation profiles is still unknown. Moreover, the effect of drought on biological activities of seed protein in mammalian systems is still unstudied with respect to glycation. Therefore, here we address the effects of a short-term drought on the patterns of seed protein-bound AGEs and accompanying alterations in pro-inflammatory properties of seed protein in the context of seed metabolome dynamics. A short-term drought, simulated as polyethylene glycol-induced osmotic stress and applied at the stage of seed filling, resulted in the dramatic suppression of primary seed metabolism, although the secondary metabolome was minimally affected. This was accompanied with significant suppression of NF-kB activation in human SH-SY5Y neuroblastoma cells after a treatment with protein hydrolyzates, isolated from the mature seeds of drought-treated plants. This effect could not be attributed to formation of known AGEs. Most likely, the prospective anti-inflammatory effect of short-term drought is related to antioxidant effect of unknown secondary metabolite protein adducts, or down-regulation of unknown plant-specific AGEs due to suppression of energy metabolism during seed filling.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 567
TI  - HPTLC-DESI-HRMS-Based Profiling of Anthraquinones in Complex Mixtures—A Proof-of-Concept Study Using Crude Extracts of Chilean Mushrooms
JO  - Foods
PY  - 2020
SP  - 156
AU  - Laub, A.
AU  - Sendatzki, A.-K.
AU  - Palfner, G.
AU  - Wessjohann, L. A.
AU  - Schmidt, J.
AU  - Arnold, N.
AU  - 
VL  - 9
UR  - 
DO  - 10.3390/foods9020156
AB  - High-performance thin-layer chromatography (HPTLC) coupled with negative ion desorption electrospray ionization high-resolution mass spectrometry (DESI-HRMS) was used for the analysis of anthraquinones in complex crude extracts of Chilean dermocyboid Cortinarii. For this proof-of-concept study, the known anthraquinones emodin, physcion, endocrocin, dermolutein, hypericin, and skyrin were identified by their elemental composition. HRMS also allowed the differentiation of the investigated anthraquinones from accompanying compounds with the same nominal mass in the crude extracts. An investigation of the characteristic fragmentation pattern of skyrin in comparison with a reference compound showed, exemplarily, the feasibility of the method for the determination of these coloring, bioactive and chemotaxonomically important marker compounds. Accordingly, we demonstrate that the coupling of HPTLC with DESI-HRMS represents an advanced and efficient technique for the detection of anthraquinones in complex matrices. This analytical approach may be applied in the field of anthraquinone-containing food and plants such as Rheum spp. (rhubarb), Aloe spp., Morinda spp., Cassia spp. and others. Furthermore, the described method can be suitable for the analysis of anthraquinone-based colorants and dyes, which are used in the food, cosmetic, and pharmaceutical industry.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 563
TI  - Cardenolide glycosides from Streptocaulon tomentosum WIGHT &amp; ARNOTT(Asclepiadaceae) in MYANMAR
JO  - J. Myanmar Acad. Arts Sci.
PY  - 2020
SP  - 1-11
AU  - Khine, M. M.
AU  - Arnold, N.
AU  - Franke, K.
AU  - Wessjohann, L. A.
AU  - 
VL  - XVIII No. 1A
UR  - 
AB  - This  paper describes  the isolation and comparative studies on NMR spectra of cardenolide glycosides from Streptocaulon tomentosum Wight &amp; Arnott (Asclepiadaceae).  Nine cardenolides were isolated from the roots of Streptocaulon tomentosum. by column chromatography and identified by NMR spectroscopy. They are 17α-H-periplogenin, 17α-H-periplogenin-β-D digitoxose,17α-H-periplogenin-β-D cymarose, 17α-H-periplogenin-β-glucosyl-(1-4)-2-O-acetyl-digitalose, 17β-H-periplogenin, 17β-H-periplogenin-β-D digitoxose, 17β-H-periplogenin-β-D cymarose, 17α -H-digitoxigenin, and 17 α-H-digitoxigenin-β-D-digitoxoside. Comparative studies on NMR spectra of cardenolide glycosides were carried out. Six cardenolides isolated from Streptocaulon tomentosum were tested for their antiproliferative activity in vitro against MCF-7 (human breast cancer cell line) and L 929 (mouse fibroblast cell line). Among these six cardenolides, 17α-H-periplogenin-3-O-β-D-digitoxoside and 17α-H-periplogenin-3-O-β-D-cymaroside exhibit significant antiproliferative activity (IC50 values, &lt; 1μM) against MCF-7. Four cardenolides  were examined for their cellular viability in the tumor cell and  U 937  (human leukemic cell line) at concentrations 100 μM, 10 μM, and 1 μM. All these four cardenolides  show the induction of apoptosis at 100 μM and 10 μM in both cell lines.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 562
TI  - Cichorins D–F: Three New Compounds from Cichorium intybus and Their Biological Effects
JO  - Molecules
PY  - 2020
SP  - 4160
AU  - Khan, M. F.
AU  - Nasr, F. A.
AU  - Noman, O. M.
AU  - Alyhya, N. A.
AU  - Ali, I.
AU  - Saoud, M.
AU  - Rennert, R.
AU  - Dube, M.
AU  - Hussain, W.
AU  - Green, I. R.
AU  - Basudan, O. A. M.
AU  - Ullah, R.
AU  - Anazi, S. H.
AU  - Hussain, H.
AU  - 
VL  - 25
UR  - https://doi.org/10.3390/molecules25184160
DO  - 10.3390/molecules25184160
AB  - Cichorium intybus L., (chicory) is employed in various traditional medicines to treat a wide range of diseases and disorders. In the current investigation, two new naphthalane derivatives viz., cichorins D (1) and E (2), along with one new anthraquinone cichorin F (3), were isolated from Cichorium intybus. In addition, three previously reported compounds viz., β-sitosterol (4), β-sitosterol β-glucopyranoside (5), and stigmasterol (6) were also isolated from Cichorium intybus. Their structures were established via extensive spectroscopic data, including 1D (1H and 13C) and 2D NMR (COSY, HSQC and HMBC), and ESIMS. Cichorin E (2) has a weak cytotoxic effect on breast cancer cells (MDA-MB-468: IC50: 85.9 µM) and Ewing’s sarcoma cells (SK-N-MC: IC50: 71.1 µM); cichorin F (3) also illustrated weak cytotoxic effects on breast cancer cells (MDA-MB-468: IC50: 41.0 µM and MDA-MB-231: IC50: 45.6 µM), and SK-N-MC cells (IC50: 71.9 µM). Moreover compounds 1–3 did not show any promising anthelmintic effects.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 561
TI  - Natural Polyketides Isolated from the Endophytic Fungus
                        Phomopsis sp. CAM212 with a Semisynthetic Derivative Downregulating
                    the ERK/IκBα Signaling Pathways
JO  - Planta Med.
PY  - 2020
SP  - 1032-1042
AU  - Jouda, J.-B.
AU  - Njoya, E. M.
AU  - Fobofou, S. A. T.
AU  - Zhou, Z. Y.
AU  - Qiang, Z.
AU  - Mbazoa, C. D.
AU  - Brandt, W.
AU  - Zhang, G.-l.
AU  - Wandji, J.
AU  - Wang, F.
AU  - 
VL  - 86
UR  - https://www.thieme-connect.com/products/ejournals/abstract/10.1055/a-1212-2930
DO  - 10.1055/a-1212-2930
AB  - AbstractThree previously undescribed natural products, phomopsinin A – C
                        (1 – 3), together with three known compounds, namely,
                        cis-hydroxymellein (4), phomoxanthone A (5) and
                    cytochalasin L-696,474 (6), were isolated from the solid culture of
                        Phomopsis sp. CAM212, an endophytic fungus obtained from Garcinia
                        xanthochymus. Their structures were determined on the basis of
                    spectroscopic data, including IR, NMR, and MS. The absolute configurations of
                        1 and 2 were assigned by comparing their experimental and
                    calculated ECD spectra. Acetylation of compound 1 yielded 1a, a
                    new natural product derivative that was tested together with other isolated
                    compounds on lipopolysaccharide-stimulated RAW 264.7 cells. Cytochalasin
                    L-696,474 (6) was found to significantly inhibit nitric oxide production,
                    but was highly cytotoxic to the treated cells, whereas compound 1
                    slightly inhibited nitric oxide production, which was not significantly
                    different compared to lipopolysaccharide-treated cells. Remarkably, the
                    acetylated derivative of 1, compound 1a, significantly inhibited
                    nitric oxide production with an IC50 value of 14.8 µM and no
                    cytotoxic effect on treated cells, thereby showing the importance of the acetyl
                    group in the anti-inflammatory activity of 1a. The study of the mechanism
                    of action revealed that 1a decreases the expression of inducible nitric
                    oxide synthase, cyclooxygenase 2, and proinflammatory cytokine IL-6 without an
                    effect on IL-1β expression. Moreover, it was found that 1a exerts
                    its anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7
                    macrophage cells by downregulating the activation of ERK1/2 and by preventing
                    the translocation of nuclear factor κB. Thus, derivatives of phomopsinin
                    A (1), such as compound 1a, could provide new anti-inflammatory
                    leads.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 559
TI  - Synthetic Studies towards Fungal glycosides: An Overview
JO  - Curr. Org. Chem.
PY  - 2020
SP  - 2865-2901
AU  - Hussain, H.
AU  - Ali, I.
AU  - Elizbit, .
AU  - Hussain, W.
AU  - Mamadalieva, N. Z.
AU  - Hussain, A.
AU  - Ali, M.
AU  - Ahmed, I.
AU  - Ullah, I.
AU  - Green, I. R.
AU  - 
VL  - 24
UR  - https://www.eurekaselect.com/187638/article
DO  - 10.2174/1385272824999201105160034
AB  - Fungi have provided intriguing chemical diversity and have additionally proven to
be a tremendous source for a great variety of therapeutic molecules. Various fungal glycosides
have been reported from fungi and the majority of these metabolites possess cytotoxic and
antimicrobial effects. Although natural products are obtained in most cases in small amounts
from the specific natural source, total syntheses of these valuable commodities remain one of
the most important ways of obtaining them on a large scale for more detailed and comprehensive
biological studies. In addition, the total synthesis of secondary metabolites is a useful
tool, not only for the disclosure of novel complex pharmacologically active molecules but also
for the establishment of cutting-edge methodologies in synthetic chemistry. Numerous fungal
glycosides have been synthesized in the last four decades regarding the following natural
product classes viz., tetramic acid glycosides (epicoccamides A and D), polyketide glycosides (TMC-151C), 2-pyrone
glycosides (epipyrone A), diterpene glycosides (sordarin), depside glycosides (CRM646-A and –B, KS-501 and KS-
502), caloporosides (caloporoside A), glycolipids (emmyguyacins A and B, acremomannolipin A), and cerebrosides
(cerebroside B, Asperamide B, phalluside-1, Sch II). The current literature review about fungal glycoside synthetic
studies is, therefore, of interest for a wide range of scientists and researchers in the field of organic, natural product,
and medicinal chemists as it outlines key strategies of fungal glycosides and, in particular, glycosylation, the known
biological and pharmacological effects of these natural compounds have afforded a new dimension of exposure.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 558
TI  - Ethnopharmacological survey of herbal remedies used in the treatment of hepatitis
JO  - Ethnobot. Res. App.
PY  - 2020
SP  - 1-29
AU  - Hussain, W.
AU  - Batool, S.
AU  - Bahar, S.
AU  - Shahida, B.
AU  - Bangash, B.
AU  - Ali, A.
AU  - Hussain, H.
AU  - Ali, I.
AU  - Ali, M.
AU  - Bussmann, R. W.
AU  - 
VL  - 20
UR  - https://www.researchgate.net/publication/344295669_Ethnopharmacological_survey_of_herbal_remedies_used_in_the_treatment_of_hepatitis
DO  - 10.32859/era.20.24.1-29
AB  - Background: Hepatitis is a serious illness and can be fatal, which has 
caused a dangerous ratio round the globe especially in the developed and underdeveloping countries. About 1.4 million deaths are reported each year from the different types of hepatitis especially hepatitis B virus (HBV) and hepatitis C virus (HCV) which cause 90% mortality and the other 10% deaths are caused due to all other hepatitis types. Methods: By using different online database such as Google scholar, Science Direct Navigator, ISI Web of Knowledge, Elsevier, springer link, Test databases, research gate and PubMed, date were retrieved by giving different keywords. Various keywords were used on plants used 
traditionally to treat hepatitis. Results: A total of 128 medicinal 
plant species were identified, belonging to 108 genera and 61 botanical 
families by reviewing 220 research articles. From the study, it showed 
that the medicinal plants are used from the very ancient time to cure 
hepatitis worldwide. These medicinal plants are used in different parts 
of the world as a traditional herbal medicine for the control of 
hepatitis. Conclusion: Our literature review will help the scientific 
communities to identify anti-hepatitis plant in order to isolate novel 
anti-hepatitis natural products.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 557
TI  - 4-Benzyloxylonchocarpin and Muracatanes A-C from Ranunculus muricatus L. and Their Biological Effects
JO  - Biomolecules
PY  - 2020
SP  - 1562
AU  - Hussain, H.
AU  - Ali, I.
AU  - Wang, D.
AU  - Mamadalieva, N. Z.
AU  - Hussain, W.
AU  - Csuk, R.
AU  - Loesche, A.
AU  - Fischer, L.
AU  - Staerk, D.
AU  - Anam, S.
AU  - AlZain, M. N.
AU  - Mushtaq, M.
AU  - Ul-Haq, Z.
AU  - Ullah, R.
AU  - Noman, O. M.
AU  - Abbas, G.
AU  - Green, I. R.
AU  - 
VL  - 10
UR  - 
DO  - 10.3390/biom10111562
AB  - Ranunculus muricatus L. is a spiny fruit buttercup that is used in various traditional medicinal systems. In the current investigation of R. muricatus, the new chalcone 4-benzyloxylonchocarpin (1), the new anthraquinone muracatanes A (2), the new-to-nature anthraquinone muracatanes B (3), and the new naphthalene analog muracatanes C (4) were isolated, in addition to the three previously reported compounds, 4-methoxylonchocarpin (5), β-sitosterol (6), and β-sitosterol β-D-glucopyranoside (7). Their structures were elucidated using 1D (1H and 13C) and 2D (COSY, HSQC, and HMBC) NMR spectroscopy and HR-ESI-MS. Chalcone 1 showed potent acetylcholinesterase inhibitory effects with Ki of 5.39 µM and Ki′ of 3.54 µM, but none of the isolated compounds showed inhibitory activity towards butyrylcholinesterase. Anthraquinone 3 illustrated α-glucosidase inhibitory effects with IC50-values of 164.46 ± 83.04 µM. Compound 5 displayed moderate cytotoxic activity towards ovarian carcinoma (A2780, IC50 = 25.4 µM), colorectal adenocarcinoma (HT29, IC50 = 20.2 µM), breast cancer (MCF7, IC50 = 23.7 µM), and thyroid carcinoma (SW1736, IC50 = 26.2 µM) while it was inactive towards pharynx carcinoma (FaDu: IC50 &gt; 30 µM).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 556
TI  - Expanding the Scope of Ugi Multicomponent Bioconjugation to Produce Pneumococcal Multivalent Glycoconjugates as Vaccine Candidates
JO  - Bioconjugate Chem.
PY  - 2020
SP  - 2231-2240
AU  - Humpierre, A. R.
AU  - Zanuy, A.
AU  - Saenz, M.
AU  - Garrido, R.
AU  - Vasco, A. V.
AU  - Pérez-Nicado, R.
AU  - Soroa-Milán, Y.
AU  - Santana-Mederos, D.
AU  - Westermann, B.
AU  - Vérez-Bencomo, V.
AU  - Méndez, Y.
AU  - García-Rivera, D.
AU  - Rivera, D. G.
AU  - 
VL  - 31
UR  - 
DO  - 10.1021/acs.bioconjchem.0c00423
AB  - Conjugate vaccines against encapsulated pathogens like Streptococcus pneumoniae face many challenges, including the existence of multiple serotypes with a diverse global distribution that constantly requires new formulations and higher coverage. Multivalency is usually achieved by combining capsular polysaccharide–protein conjugates from invasive serotypes, and for S. pneumoniae, this has evolved from 7- up to 20-valent vaccines. These glycoconjugate formulations often contain high concentrations of carrier proteins, which may negatively affect glycoconjugate immune response. This work broadens the scope of an efficient multicomponent strategy, leading to multivalent pneumococcal glycoconjugates assembled in a single synthetic operation. The bioconjugation method, based on the Ugi four-component reaction, enables the one-pot incorporation of two different polysaccharide antigens to a tetanus toxoid carrier, thus representing the fastest approach to achieve multivalency. The reported glycoconjugates incorporate three combinations of capsular polysaccharides 1, 6B, 14, and 18C from S. pneumoniae. The glycoconjugates were able to elicit functional specific antibodies against pneumococcal strains comparable to those shown by mixtures of the two monovalent glycoconjugates.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 555
TI  - Evaluation of plant sources for antiinfective lead compound discovery by correlating phylogenetic, spatial, and bioactivity data
JO  - Proc. Natl. Acad. Sci. U.S.A.
PY  - 2020
SP  - 12444-12451
AU  - Holzmeyer, L.
AU  - Hartig, A.-K.
AU  - Franke, K.
AU  - Brandt, W.
AU  - Muellner-Riehl, A. N.
AU  - Wessjohann, L. A.
AU  - Schnitzler, J.
AU  - 
VL  - 117
UR  - 
DO  - 10.1073/pnas.1915277117
AB  - The continued high rates of using antibiotics in healthcare and livestock, without sufficient new compounds reaching the market, has led to a dramatic increase in antimicrobial resistance, with multidrug-resistant bacteria emerging as a major public health threat worldwide. Because the vast majority of antiinfectives are natural products or have originated from them, we assessed the predictive power of plant molecular phylogenies and species distribution modeling in the search for clades and areas which promise to provide a higher probability of delivering new antiinfective compound leads. Our approach enables taxonomically and spatially targeted bioprospecting and supports the battle against the global antimicrobial crisis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 554
TI  - Calcium‐dependent protein kinase 5 links calcium‐signaling with N‐Hydroxy‐L‐pipecolic acid‐ and SARD1‐dependent immune memory in systemic acquired resistance
JO  - New Phytol.
PY  - 2020
SP  - 310-325
AU  - Guerra, T.
AU  - Schilling, S.
AU  - Hake, K.
AU  - Gorzolka, K.
AU  - Sylvester, F.-P.
AU  - Conrads, B.
AU  - Westermann, B.
AU  - Romeis, T.
AU  - 
VL  - 225
UR  - 
DO  - 10.1111/nph.16147
AB  - Systemic acquired resistance (SAR) prepares infected plants for faster and stronger defense activation upon subsequent attacks. SAR requires an information relay from primary infection to distal tissue and the initiation and maintenance of a self‐maintaining phytohormone salicylic acid (SA)‐defense loop.In spatial and temporal resolution, we show that calcium‐dependent protein kinase CPK5 contributes to immunity and SAR. In local basal resistance, CPK5 functions upstream of SA synthesis, perception, and signaling. In systemic tissue, CPK5 signaling leads to accumulation of SAR‐inducing metabolite N‐hydroxy‐L‐pipecolic acid (NHP) and SAR marker genes, including Systemic Acquired Resistance Deficient 1 (SARD1)Plants of increased CPK5, but not CPK6, signaling display an ‘enhanced SAR’ phenotype towards a secondary bacterial infection. In the sard1‐1 background, CPK5‐mediated basal resistance is still mounted, but NHP concentration is reduced and enhanced SAR is lost.The biochemical analysis estimated CPK5 half maximal kinase activity for calcium, K50 [Ca2+], to be c. 100 nM, close to the cytoplasmic resting level. This low threshold uniquely qualifies CPK5 to decode subtle changes in calcium, a prerequisite to signal relay and onset and maintenance of priming at later time points in distal tissue. Our data explain why CPK5 functions as a hub in basal and systemic plant immunity.
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions
ER  - 


TY  - JOUR
ID  - 551
TI  - High-Throughput Fingerprinting of Rhizobial Free Fatty Acids by Chemical Thin-Film Deposition and Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry
JO  - Methods Protoc.
PY  - 2020
SP  - 36
AU  - Gladchuk, A.
AU  - Shumilina, J.
AU  - Kusnetsova, A.
AU  - Bureiko, K.
AU  - Billig, S.
AU  - Tsarev, A.
AU  - Alexandrova, I.
AU  - Leonova, L.
AU  - Zhukov, V. A.
AU  - Tikhonovich, I. A.
AU  - Birkemeyer, C.
AU  - Podolskaya, E.
AU  - Frolov, A.
AU  - 
VL  - 3
UR  - 
DO  - 10.3390/mps3020036
AB  - Fatty acids (FAs) represent an important class of metabolites, impacting on membrane building blocks and signaling compounds in cellular regulatory networks. In nature, prokaryotes are characterized with the most impressing FA structural diversity and the highest relative content of free fatty acids (FFAs). In this context, nitrogen-fixing bacteria (order Rhizobiales), the symbionts of legumes, are particularly interesting. Indeed, the FA profiles influence the structure of rhizobial nodulation factors, required for successful infection of plant root. Although FA patterns can be assessed by gas chromatography—(GC-) and liquid chromatography—mass spectrometry (LC-MS), sample preparation for these methods is time-consuming and quantification suffers from compromised sensitivity, low stability of derivatives and artifacts. In contrast, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) represents an excellent platform for high-efficient metabolite fingerprinting, also applicable to FFAs. Therefore, here we propose a simple and straightforward protocol for high-throughput relative quantification of FFAs in rhizobia by combination of Langmuir technology and MALDI-TOF-MS featuring a high sensitivity, accuracy and precision of quantification. We describe a step-by-step procedure comprising rhizobia culturing, pre-cleaning, extraction, sample preparation, mass spectrometric analysis, data processing and post-processing. As a case study, a comparison of the FFA metabolomes of two rhizobia species—Rhizobium leguminosarum and Sinorhizobium meliloti, demonstrates the analytical potential of the protocol.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 549
TI  - Discovery of salicyl benzoate UDP‐glycosyltransferase, a central enzyme in poplar salicinoid phenolic glycoside biosynthesis
JO  - Plant J.
PY  - 2020
SP  - 99-115
AU  - Fellenberg, C.
AU  - Corea, O.
AU  - Yan, L.
AU  - Archinuk, F.
AU  - Piirtola, E.
AU  - Gordon, H.
AU  - Reichelt, M.
AU  - Brandt, W.
AU  - Wulff, J.
AU  - Ehlting, J.
AU  - Constabel, C. P.
AU  - 
VL  - 102
UR  - 
DO  - 10.1111/tpj.14615
AB  - The salicinoids are anti‐herbivore phenolic glycosides unique to the Salicaceae (Populus and Salix). They consist of a salicyl alcohol glucoside core, which is usually further acylated with benzoic, cinnamic, or phenolic acids. While salicinoid structures are well known, their biosynthesis remains enigmatic. Recently, two enzymes from poplar, salicyl alcohol benzoyl transferase and benzyl alcohol benzoyl transferase, were shown to catalyze the production of salicyl benzoate, a predicted potential intermediate in salicinoid biosynthesis. Here, we used transcriptomics and co‐expression analysis with these two genes to identify two UDP‐glucose dependent glycosyltransferases (UGT71L1 and UGT78M1) as candidate enzymes in this pathway. Both recombinant enzymes accepted only salicyl benzoate, salicyl aldehyde, and 2‐hydroxycinnamic acid as glucose acceptors. Knocking out the UGT71L1 gene by CRISPR/Cas9 in poplar hairy root cultures led to the complete loss of salicortin, tremulacin, and tremuloidin, and a partial reduction of salicin content. This demonstrated that UGT71L1 is required for synthesis of the major salicinoids, and suggested that an additional route can lead to salicin. CRISPR/Cas9 knockouts for UGT78M1 were not successful, and its in vivo role thus remains to be determined. Although it has a similar substrate preference and predicted structure as UGT71L1, it appears not to contribute to the synthesis of salicortin, tremulacin, and tremuloidin, at least in roots. The demonstration of UGT71L1 as an enzyme of salicinoid biosynthesis will open up new avenues for the elucidation of this pathway.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 548
TI  - Metabolomics reveals impact of seven functional foods on metabolic pathways in a gut microbiota model
JO  - J. Adv. Res.
PY  - 2020
SP  - 47-59
AU  - Farag, M. A.
AU  - Abdelwareth, A.
AU  - Sallam, I. E.
AU  - el Shorbagi, M.
AU  - Jehmlich, N.
AU  - Fritz-Wallace, K.
AU  - Serena Schäpe, S.
AU  - Rolle-Kampczyk, U.
AU  - Ehrlich, A.
AU  - Wessjohann, L. A.
AU  - von Bergen, M.
AU  - 
VL  - 23
UR  - 
DO  - 10.1016/j.jare.2020.01.001
AB  - Functional food defined as dietary supplements that in addition to their nutritional values, can beneficially modulate body functions becomes more and more popular but the reaction of the intestinal microbiota to it is largely unknown. In order to analyse the impact of functional food on the microbiota itself it is necessary to focus on the physiology of the microbiota, which can be assessed in a whole by untargeted metabolomics. Obtaining a detailed description of the gut microbiota reaction to food ingredients can be a key to understand how these organisms regulate and bioprocess many of these food components. Extracts prepared from seven chief functional foods, namely green tea, black tea, Opuntia ficus-indica (prickly pear, cactus pear), black coffee, green coffee, pomegranate, and sumac were administered to a gut consortium culture encompassing 8 microbes which are resembling, to a large extent, the metabolic activities found in the human gut. Samples were harvested at 0.5 and 24 h post addition of functional food extract and from blank culture in parallel and analysed for its metabolites composition using gas chromatography coupled to mass spectrometry detection (GC-MS). A total of 131 metabolites were identified belonging to organic acids, alcohols, amino acids, fatty acids, inorganic compounds, nitrogenous compounds, nucleic acids, phenolics, steroids and sugars, with amino acids as the most abundant class in cultures. Considering the complexity of such datasets, multivariate data analyses were employed to classify samples and investigate how functional foods influence gut microbiota metabolisms. Results from this study provided a first insights regarding how functional foods alter gut metabolism through either induction or inhibition of certain metabolic pathways, i.e. GABA production in the presence of higher acidity induced by functional food metabolites such as polyphenols. Likewise, functional food metabolites i.e., purine alkaloids acted themselves as direct substrate in microbiota metabolism.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 547
TI  - Foliar Application of Chitosan Increases Tomato Growth and Influences Mycorrhization and Expression of Endochitinase-Encoding Genes
JO  - Int. J. Mol. Sci.
PY  - 2020
SP  - 535
AU  - El Amerany, F.
AU  - Meddich, A.
AU  - Wahbi, S.
AU  - Porzel, A.
AU  - Taourirte, M.
AU  - Rhazi, M.
AU  - Hause, B.
AU  - 
VL  - 21
UR  - 
DO  - 10.3390/ijms21020535
AB  - Nowadays, applying bio-organic fertilizer (e.g., chitosan, Ch) or integrating beneficial microorganisms (e.g., arbuscular mycorrhizal fungi, AMF) are among the successful strategies to promote plant growth. Here, the effect of two application modes of Ch (foliar spray or root treatment) and Ch-derived nanoparticles (NPs) on tomato plants colonized with the AMF Rhizophagus irregularis were analyzed, thereby focusing on plant biomass, flowering and mycorrhization. An increase of shoot biomass and flower number was observed in arbuscular mycorrhizal (AM) plants sprayed with Ch. The interaction with AMF, however, was reduced as shown by decreased mycorrhization rates and AM-specific gene expression. To get insights into Ch effect on mycorrhization, levels of sugars, jasmonates, abscisic acid, and the expression of two chitinase-encoding genes were determined in mycorrhizal roots. Ch had no effect on sugar and phytohormone levels, but the reduced mycorrhization was correlated with down- and upregulated expression of Chi3 and Chi9, respectively. In contrast, application of NPs to leaves and Ch applied to the soil did not show any effect, neither on mycorrhization rate nor on growth of mycorrhizal plants. Concluding, Ch application to leaves enhanced plant growth and flowering and reduced interaction with AMF, whereas root treatment did not affect these parameters.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 543
TI  - Characterization of antibacterial proanthocyanidins of Dalbergia monetaria, an amazonian medicinal plant, by UHPLC-HRMS/MS
JO  - Planta Med.
PY  - 2020
SP  - 858– 866
AU  - de Moura, P. H. B.
AU  - de Sousa, A. A.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - Leal, I. C. R.
AU  - Martins, R. C. C.
AU  - 
VL  - 86
UR  - https://doi.org/10.1055/a-1170-8016
DO  - 10.1055/a-1170-8016
AB  - Dalbergia monetaria is an Amazonian plant whose bark is widely used to treat urinary tract infections. This paper describes a bio-guided study of ethanolic extracts from the bark and leaves of D. monetaria, in a search for metabolites active against human pathogenic bacteria. In vitro assays were performed against 10 bacterial strains, highlighting methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Fractioning of the extracts was performed using instrumental and classical techniques, and samples were characterized by UHPLC-HRMS/MS. Ethyl acetate fractions from bark and leaves showed similar antibacterial activities. EAFB is enriched in isoflavone C-glucosides and EAFL enriched in proanthocyanidins. Subfractions from EAFL presented higher activity and showed a complex profile of proanthocyanidins constructed by (epi)-cassiaflavan and (epi)-catechin units, including dimers, trimers and tetramers. The fragmentation pattern emphasized the neutral loss of cassiaflavan units by quinone-methide fission. Fraction SL7-6, constituted by (ent)-cassiaflavan-(ent)-cassiaflavan-(epi)-catechin isomers, showed the lowest MIC against the S. aureus and P. aeruginosa with values corresponding to 64 and 32 µg/mL, respectively. Cassiaflavan-proanthocyanidins have not been found previously in another botanical genus, except in Cassia, and the traditional medicinal use of D. monetaria might be related to the antibacterial activity of proanthocyanidins characterized in the species.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 541
TI  - Passiflora mucronata leaves extracts obtained from different methodologies: a phytochemical study based on cytotoxic and apoptosis activities of triterpenes and phytosterols constituents
JO  - Braz. J. Pharm. Sci.
PY  - 2020
SP  - e17666
AU  - da Silva, I. C. V.
AU  - Silva, I. C. V. d.
AU  - de Oliveira, P. F.
AU  - Oliveira, P. F. d.
AU  - Barbosa, G. M.
AU  - Wessjohann, L. A.
AU  - Cardozo-Filho, L.
AU  - Holandino, C.
AU  - Muzitano, M. F.
AU  - Leal, I. C. R.
AU  - 
VL  - 56
UR  - http://dx.doi.org/10.1590/s2175-97902019000417666
DO  - 10.1590/s2175-97902019000417666
AB  - Cancer is one of the most prevalent diseases worldwide and the natural products could be a source of bioactive compounds. Passiflora mucronata (PM) belongs to a very known vegetal genus, although, there are no studies about cytotoxic activity or isolated compounds. Different extracts from PM were obtained by liquid-liquid partition (P), Soxhlet (Sox) and supercritical fluid (SFE1-5) extraction techniques, being compared concerning their yields, chemical profile and cytotoxicity. The Sox extracts showed the highest yields (6.03%: hexane; 2.51%: dichloromethane) followed by SFE (from 4.34 to 1.63%) and partitions (1.06 and 2.26%). The hexane partition (HP) showed the best cytotoxic activity against K562 cell line (IC50 = 18.72 µg.mL-1). From HP, the following compounds were identified and analysed its cytotoxic activities: β-amyrin (IC50 = 3.92 µg.mL-1), β-sitosterol (IC50 = 3.37 µg.mL-1), stigmasterol (IC50 = 3.31 µg.mL-1) and oleanolic acid. Stigmasterol induced about 75% of K562 total apoptosis. The compounds were tested against MA-104 cell line and the selective index (SI) attributed (SI &gt;10 for all compounds). This indicates good selectivity to K562 cell line at the expense of MA-104. This is the first time, identifying those compounds to PM .
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 540
TI  - Secondary metabolites of Phlebopus species from Northern Thailand
JO  - Mycol. Prog.
PY  - 2020
SP  - 1525-1536
AU  - Chuankid, B.
AU  - Schrey, H.
AU  - Thongbai, B.
AU  - Raspé, O.
AU  - Arnold, N.
AU  - Hyde, K. D.
AU  - Stadler, M.
AU  - 
VL  - 19
UR  - 
DO  - 10.1007/s11557-020-01643-y
AB  - AbstractSubmerged cultures of the edible mushrooms Phlebopus portentosus and Phlebopus spongiosus were screened for their secondary metabolites by HPLC-UV/Vis and HR-LC-ESI-MS. Two new compounds, 9′-hydroxyphenyl pulvinone (1), containing an unusual pulvinone structure, and phlebopyron (2), together with the seven known pigments, atromentic acid (3), xerocomic acid (4), variegatic acid (5), methyl atromentate (6), methyl isoxerocomate (7), methyl variegatate (8), and variegatorubin (9) were isolated from the cultures. Their structures were assigned on the basis of extensive 1D/2D NMR spectroscopic analyses, as well as HR-ESI-MS, and HR-ESI-MS/MS measurements. Furthermore, the isolated compounds were evaluated for their antimicrobial and cytotoxic properties. 9′-hydroxyphenyl pulvinone (1), xerocomic acid (4), and methyl variegatate (8) exhibited weak to moderate cytotoxic activities against several tumor cell lines. The present paper provides a comprehensive characterization of pigments from the class of pulvinic acids that are present in the basidiomes of many edible bolete species.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 539
TI  - Chemical constituents of the roots of Ormocarpum sennoides subsp. zanzibaricum
JO  - Biochem. Syst. Ecol.
PY  - 2020
SP  - 104142
AU  - Chalo, D. M.
AU  - Kakudidi, E.
AU  - Origa-Oryem, H.
AU  - Namukobe, J.
AU  - Franke, K.
AU  - Yenesew, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 93
UR  - https://doi.org/10.1016/j.bse.2020.104142
DO  - 10.1016/j.bse.2020.104142
AB  - Phytochemical investigation of the roots of O. sennoides subsp. zanzibaricum Brenan &amp; J.B. Gillett resulted in the isolation of three biflavonoids (trime-chamaejasmin, (+)- chamaejasmin, (+)-liquiritigeninyl-(I-3,II-3)-naringenin), one bi-4-phenyldihydrocoumarin (diphysin), one isoflavan (glabridin), one triterpenoid (3-O-acetyloleanoic acid) and a phytosterol (β-sitosterol). Compounds were identified by detailed MS, 1D and 2D NMR spectroscopic analyses. Their absolute configurations were elucidated based on ECD spectra. The previously undescribed trime-chamaejasmin represents a bis-epi-chamaejasmenin C diastereomer. The chemophenetic significance is discussed in detail. The results contribute to the phytochemical characterization of the genus Ormocarpum and suggest a close chemophenetic relationship with other genera within the subfamily Papilionoideae. Furthermore, this report provides baseline data for comparing the two infraspecific taxa of O. sennoides (Willd.) DC.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 538
TI  - Enzymatic activity and thermoresistance of improved microbial transglutaminase variants
JO  - Amino Acids
PY  - 2020
SP  - 313-326
AU  - Böhme, B.
AU  - Moritz, B.
AU  - Wendler, J.
AU  - Hertel, T. C.
AU  - Ihling, C.
AU  - Brandt, W.
AU  - Pietzsch, M.
AU  - 
VL  - 52
UR  - 
DO  - 10.1007/s00726-019-02764-9
AB  - Microbial transglutaminase (MTG, EC 2.3.2.13) of Streptomyces mobaraensis is widely used in industry for its ability to synthesize isopeptide bonds between the proteinogenic side chains of glutamine and lysine. The activated wild-type enzyme irreversibly denatures at 60 °C with a pseudo-first-order kinetics and a half-life time (t1/2) of 2 min. To increase the thermoresistance of MTG for higher temperature applications, we generated 31 variants based on previous results obtained by random mutagenesis, DNA shuffling and saturation mutagenesis. The best variant TG16 with a specific combination of five of seven substitutions (S2P, S23Y, S24 N, H289Y, K294L) shows a 19-fold increased half-life at 60 °C (t1/2 = 38 min). As measured by differential scanning fluorimetry, the transition point of thermal unfolding was increased by 7.9 °C. Also for the thermoresistant variants, it was shown that inactivation process follows a pseudo-first-order reaction which is accompanied by irreversible aggregation and intramolecular self-crosslinking of the enzyme. Although the mutations are mostly located on the surface of the enzyme, kinetic constants determined with the standard substrate CBZ-Gln-Gly-OH revealed a decrease in KM from 8.6 mM (± 0.1) to 3.5 mM (± 0.1) for the recombinant wild-type MTG and TG16, respectively. The improved performance of TG16 at higher temperatures is exemplary demonstrated with the crosslinking of the substrate protein β-casein at 60 °C. Using molecular dynamics simulations, it was shown that the increased thermoresistance is caused by a higher backbone rigidity as well as increased hydrophobic interactions and newly formed hydrogen bridges.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 535
TI  - Fingolimod as a Treatment in Neurologic Disorders Beyond Multiple Sclerosis
JO  - Drugs R. D.
PY  - 2020
SP  - 197-207
AU  - Bascuñana, P.
AU  - Möhle, L.
AU  - Brackhan, M.
AU  - Pahnke, J.
AU  - 
VL  - 20
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419396/
DO  - 10.1007/s40268-020-00316-1
AB  - Fingolimod is an approved treatment for relapsing–remitting multiple sclerosis (MS), and its properties in different pathways have raised interest in therapy research for other neurodegenerative diseases. Fingolimod is an agonist of sphingosine-1-phosphate (S1P) receptors. Its main pharmacologic effect is immunomodulation by lymphocyte homing, thereby reducing the numbers of T and B cells in circulation. Because of the ubiquitous expression of S1P receptors, other effects have also been described. Here, we review preclinical experiments evaluating the effects of treatment with fingolimod in neurodegenerative diseases other than MS, such as Alzheimer’s disease or epilepsy. Fingolimod has shown neuroprotective effects in different animal models of neurodegenerative diseases, summarized here, correlating with increased brain-derived neurotrophic factor and improved disease phenotype (cognition and/or motor abilities). As expected, treatment also induced reductions in different neuroinflammatory markers because of not only inhibition of lymphocytes but also direct effects on astrocytes and microglia. Furthermore, fingolimod treatment exhibited additional effects for specific neurodegenerative disorders, such as reduction of amyloid-β production, and antiepileptogenic properties. The neuroprotective effects exerted by fingolimod in these preclinical studies are reviewed and support the translation of fingolimod into clinical trials as treatment in neurodegenerative diseases beyond neuroinflammatory conditions (MS).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 532
TI  - Glucagon and Glucagon-like Peptide-1 Receptors: Promising Therapeutic Targets for an Effective Management of Diabetes Mellitus
JO  - Curr. Pharm. Des.
PY  - 2020
SP  - 501-508
AU  - Abbas, G.
AU  - Haq, Q. M. I.
AU  - Hamaed, A.
AU  - Al-Sibani, M.
AU  - Hussain, H.
AU  - 
VL  - 26
UR  - 
DO  - 10.2174/1381612826666200131143231
AB  - G-protein-coupled receptors (GPCRs) are membrane-bound proteins which are responsible for the detection of extracellular stimuli and the origination of intracellular responses. Both glucagon and glucagon-like peptide-1 (GLP-1) receptors belong to G protein-coupled receptor (GPCR) superfamily. Along with insulin, glucagon and GLP-1 are critical hormones for maintaining normal serum glucose within human body. Glucagon generally plays its role in the liver through cyclic adenosine monophosphate (cAMP), where it compensates the action of insulin. GLP-1 is secreted by the L-cells of the small intestine to stimulate insulin secretion and inhibit glucagon action. Despite the extensive research efforts and the multiple approaches adopted, the glycemic control in the case of type-2 diabetes mellitus remains a major challenge. Therefore, a deep understanding of the structure-function relationship of these receptors will have great implications on future therapies in order to maintain a normal glucose level for an extended period of time. The antagonists of glucagon receptor that can effectively block the hepatic glucose production, as a result of glucagon action, are highly desirable for the tuning of the hyperglycemic state in type 2 diabetes mellitus. In the same manner, GLP-1R agonists act as important treatment modalities thanks to their multiple anti-diabetic actions to attain normal glucose level. In this review article, the structural diversity of glucagon and GLP-1 receptors along with their signaling pathways, site-directed mutations and significance in drug discovery against type-2 diabetes will be illustrated. Moreover, the promising non-peptide antagonists of glucagon receptor and agonists of GLP-1 receptor, for the management of diabetes will be presented with elaboration on the structure-activity relationship (SAR).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 623
TI  - Imaging P-Glycoprotein Induction at the Blood–Brain Barrier of a β-Amyloidosis Mouse Model with 11C-Metoclopramide PET
JO  - J. Nucl. Med.
PY  - 2020
SP  - 1050-1057
AU  - Zoufal, V.
AU  - Mairinger, S.
AU  - Brackhan, M.
AU  - Krohn, M.
AU  - Filip, T.
AU  - Sauberer, M.
AU  - Stanek, J.
AU  - Wanek, T.
AU  - Tournier, N.
AU  - Bauer, M.
AU  - Pahnke, J.
AU  - Langer, O.
AU  - 
VL  - 61
UR  - https://doi.org/10.2967/jnumed.119.237198
DO  - 10.2967/jnumed.119.237198
AB  - P-glycoprotein (ABC subfamily B member 1, ABCB1) plays an important role at the blood-brain barrier (BBB) in promoting clearance of neurotoxic β-amyloid (Aβ) peptides from the brain into the blood. ABCB1 expression and activity were found to be decreased in the brains of Alzheimer disease patients. Treatment with drugs that induce cerebral ABCB1 activity may be a promising approach to delay the build-up of Aβ deposits in the brain by enhancing clearance of Aβ peptides from the brain. The aim of this study was to investigate whether PET with the weak ABCB1 substrate radiotracer 11C-metoclopramide can measure ABCB1 induction at the BBB in a β-amyloidosis mouse model (APP/PS1-21 mice) and in wild-type mice. Methods: Groups of wild-type and APP/PS1-21 mice aged 50 or 170 d underwent 11C-metoclopramide baseline PET scans or scans after intraperitoneal treatment with the rodent pregnane X receptor activator 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN, 25 mg/kg) or its vehicle over 7 d. At the end of the PET scans, brains were harvested for immunohistochemical analysis of ABCB1 and Aβ levels. In separate groups of mice, radiolabeled metabolites of 11C-metoclopramide were determined in plasma and brain at 15 min after radiotracer injection. As an outcome parameter of cerebral ABCB1 activity, the elimination slope of radioactivity washout from the brain (k E,brain) was calculated. Results: PCN treatment resulted in an increased clearance of radioactivity from the brain as reflected by significant increases in k E,brain (from +26% to +54% relative to baseline). Immunohistochemical analysis confirmed ABCB1 induction in the brains of PCN-treated APP/PS1-21 mice with a concomitant decrease in Aβ levels. There was a significant positive correlation between k E,brain and ABCB1 levels in the brain. In wild-type mice, a significant age-related decrease in k E,brain was found. Metabolite analysis showed that most radioactivity in the brain comprised unmetabolized 11C-metoclopramide in all animal groups. Conclusion: 11C-metoclopramide can measure ABCB1 induction in the mouse brain without the need to consider an arterial input function and may find potential application in Alzheimer disease patients to noninvasively evaluate strategies to enhance the clearance properties of the BBB.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 622
TI  - Age dependency of cerebral P-glycoprotein function in wild-type and APPPS1 mice measured with PET
JO  - J. Cereb. Blood Flow Metab.
PY  - 2020
SP  - 150-162
AU  - Zoufal, V.
AU  - Wanek, T.
AU  - Krohn, M.
AU  - Mairinger, S.
AU  - Filip, T.
AU  - Sauberer, M.
AU  - Stanek, J.
AU  - Pekar, T.
AU  - Bauer, M.
AU  - Pahnke, J.
AU  - Langer, O.
AU  - 
VL  - 40
UR  - 
DO  - 10.1177/0271678X18806640
AB  - P-glycoprotein (P-gp, ABCB1) is an efflux transporter at the blood–brain barrier (BBB), which mediates clearance of beta-amyloid (Aβ) from brain into blood. We used (R)-[11C]verapamil PET in combination with partial P-gp inhibition with tariquidar to measure cerebral P-gp function in a beta-amyloidosis mouse model (APPtg) and in control mice at three different ages (50, 200 and 380 days). Following tariquidar pre-treatment (4 mg/kg), whole brain-to-plasma radioactivity concentration ratios (Kp,brain) were significantly higher in APPtg than in wild-type mice aged 50 days, pointing to decreased cerebral P-gp function. Moreover, we found an age-dependent decrease in cerebral P-gp function in both wild-type and APPtg mice of up to −50%. Alterations in P-gp function were more pronounced in Aβ-rich brain regions (hippocampus, cortex) than in a control region with negligible Aβ load (cerebellum). PET results were confirmed by immunohistochemical staining of P-gp in brain microvessels. Our results confirm previous findings of reduced P-gp function in Alzheimer’s disease mouse models and show that our PET protocol possesses adequate sensitivity to measure these functional changes in vivo. Our PET protocol may find use in clinical studies to test the efficacy of drugs to induce P-gp function at the human BBB to enhance Aβ clearance.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 621
TI  - Chemical profiling and discrimination of essential oils from six Ferula species using GC analyses coupled with chemometrics and evaluation of their antioxidant and enzyme inhibitory potential
JO  - Antibiotics
PY  - 2020
SP  - 518
AU  - Youssef, F. S.
AU  - Mamatkhanova, M. A.
AU  - Mamadalieva, N. Z.
AU  - Zengin, G.
AU  - Aripova, S. F.
AU  - Alshammari, E.
AU  - Ashour, M. L.
AU  - 
VL  - 9
UR  - https://www.mdpi.com/2079-6382/9/8/518
DO  - 10.3390/antibiotics9080518
AB  - The differences in the composition of essential oils obtained from the aerial parts of six Ferula species viz., F. caratavica (Fc), F. kuchistanica (Fk), F. pseudoreoselinum (Fp), F. samarcandica (Fs), F. tenuisecta (Ft) and F. varia (Fv) were detected both qualitatively and semi-quantitatively using GC-MS and GC-FID analyses. One hundred and six metabolites were identified that account for 92.1, 96.43, 87.43, 95.95, 92.90 and 89.48% of Fc, Fk, Fp, Fs, Ft and Fv whole essential oils, respectively. The data from the GC-MS analyses were subjected to unsupervised pattern recognition chemometric analysis utilizing principal component analysis (PCA) to improve the visualization of such differences among the six species. Fk and Ft are very closely related to each other and were gathered together in one cluster. The antioxidant potential was assessed in vitro using different assays including 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing power (FRAP) and phosphomolybdenum (PM) assays. Ft and Fp exhibited the most notable antioxidant properties as evidenced by their pronounced activities in most of the antioxidant assays performed, followed by Fc. Fk showed the most effective tyrosinase inhibitory potential, which was estimated as 119.67 mgKAE/g oil, while Fp exhibited the most potent α-amylase inhibitory potential, which was equivalent to 2.61 mmol ACAE/g oil. Thus, it was concluded that Ferula species could serve as a promising natural antioxidant drug that could be included in different products and spices to alleviate hyperglycemia and used as a natural ingredient in pharmaceutical cosmetics to counteract hyperpigmentation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 614
TI  - Synthesis of Lactam-Bridged and Lipidated Cyclo-Peptides as Promising Anti-Phytopathogenic Agents
JO  - Molecules
PY  - 2020
SP  - 811
AU  - Vasco, A. V.
AU  - Brode, M.
AU  - Méndez, Y.
AU  - Valdés, O.
AU  - Rivera, D. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 25
UR  - 
DO  - 10.3390/molecules25040811
AB  - Antimicrobial resistance to conventional antibiotics and the limited alternatives to combat plant-threatening pathogens are worldwide problems. Antibiotic lipopeptides exert remarkable membrane activity, which usually is not prone to fast resistance formation, and often show organism-type selectivity. Additional modes of action commonly complement the bioactivity profiles of such compounds. The present work describes a multicomponent-based methodology for the synthesis of cyclic polycationic lipopeptides with stabilized helical structures. The protocol comprises an on solid support Ugi-4-component macrocyclization in the presence of a lipidic isocyanide. Circular dichroism was employed to study the influence of both macrocyclization and lipidation on the amphiphilic helical structure in water and micellar media. First bioactivity studies against model phytopathogens demonstrated a positive effect of the lipidation on the antimicrobial activity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 613
TI  - Insights into the secondary structures of lactam N-substituted stapled peptides
JO  - Org. Biomol. Chem.
PY  - 2020
SP  - 3838-3842
AU  - Vasco, A. V.
AU  - Moya, C. G.
AU  - Gröger, S.
AU  - Brandt, W.
AU  - Balbach, J.
AU  - Pérez, C. S.
AU  - Wessjohann, L. A.
AU  - Rivera, D. G.
AU  - 
VL  - 18
UR  - 
DO  - 10.1039/D0OB00767F
AB  - Stapled peptides derived from the Ugi macrocyclization comprise a special class of cyclopeptides with an N-substituted lactam bridge cross-linking two amino acid side chains. Herein we report a comprehensive analysis of the structural factors influencing the secondary structure of these cyclic peptides in solution. Novel insights into the s-cis/s-trans isomerism and the effect of N-functionalization on the conformation are revealed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 612
TI  - Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing
JO  - Pharmaceuticals
PY  - 2020
SP  - 94
AU  - Ur Rehman, N.
AU  - Halim, S. A.
AU  - Khan, M.
AU  - Hussain, H.
AU  - Yar Khan, H.
AU  - Khan, A.
AU  - Abbas, G.
AU  - Rafiq, K.
AU  - Al-Harrasi, A.
AU  - 
VL  - 13
UR  - 
DO  - 10.3390/ph13050094
AB  - Lycium shawii Roem. &amp; Schult and resin of Aloe vera (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the isolation of 14 known compounds, viz., 1–9 from L. shawii and 10–20 from A. vera. Their structures were confirmed by combined spectroscopic techniques including 1D (1H and 13C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS). The cytotoxic potential of isolates was tested against the triple-negative breast cancer cell line (MDA-MB-231). Compound 5 exhibited excellent antiproliferative activity in a range of 31 μM, followed by compounds 1–3, 7, and 12, which depicted IC50 values in the range of 35–60 μM, while 8, 6, and 9 also demonstrated IC50 values &gt;72 μM. Subsequently, in silico target fishing was applied to predict the most potential cellular drug targets of the active compounds, using pharmacophore modeling and inverse molecular docking approach. The extensive in silico analysis suggests that our compounds may target carbonic anhydrase II (CA-II) to exert their anticancer activities. When tested on CA-II, compounds 5 (IC50 = 14.4 µM), 12 (IC50 = 23.3), and 2 (IC50 = 24.4 µM) showed excellent biological activities in vitro. Additionally, the ethyl acetate fraction of both plants showed promising antioxidant activity. Among the isolated compounds, 4 possesses the highest antioxidant (55 μM) activity followed by 14 (241 μM). The results indicated that compound 4 can be a promising candidate for antioxidant drugs, while compound 5 is a potential candidate for anticancer drugs.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 611
TI  - A New Anticancer Bisflavan-3-Ol from Boerhavia elegans
JO  - Chem. Nat. Compd.
PY  - 2020
SP  - 235-238
AU  - Ur Rehman, N.
AU  - Hussain, H.
AU  - Khan, H. Y.
AU  - Abbas, G.
AU  - Hidayatullah, .
AU  - Al-Harrasi, A.
AU  - 
VL  - 56
UR  - 
DO  - 10.1007/s10600-020-02995-3
AB  - A new a bisflavan-3-ol, boerhavianane (1), was isolated from Boerhavia elegans L. The structure of the flavanol dimer was elucidated by detailed spectroscopic analysis including 1H, 13C NMR, COSY, HMQC, HMBC, and ESI-MS. Boerhavianane (1) was evaluated for its anticancer activity and demonstrated a significant reduction in the viability of breast cancer cells in a concentration-dependent manner with an IC50 value of 38.48 μg/mL. Moreover, boerhavianane (1) was also screened for DPPH antioxidant activity and acetyl cholinesterase, xanthine oxidase, urease, and α-glucosidase enzyme inhibition activities. Preliminary results showed that it exhibited significant inhibition (81.0 ± 2.0%) against urease enzyme, whereas for DPPH radical scavenging it showed moderate activity (75.0 ± 1.5%).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 609
TI  - Mesomeric form of quaternary indoloquinazoline alkaloid and other constituents from the Cameroonian Rutaceae Araliopsis soyauxii Engl.
JO  - Biochem. Syst. Ecol.
PY  - 2020
SP  - 104050
AU  - Tchatchouang Noulala, C. G.
AU  - Fotso, G. W.
AU  - Rennert, R.
AU  - Lenta, B. N.
AU  - Sewald, N.
AU  - Arnold, N.
AU  - Happi, E. N.
AU  - Ngadjui, B. T.
AU  - 
VL  - 91
UR  - 
DO  - 10.1016/j.bse.2020.104050
AB  - A mesomeric form of quaternary indoloquinazoline alkaloid, soyauxinium chloride (1) was obtained through the chemical investigation of stem bark and roots of Araliopsis soyauxii Engl. [syn. Vepris soyauxii (Engl.) Mziray] (Rutaceae) together with fifteen known compounds, including three furoquinoline alkaloids, three 2-quinolones, two limonoids, two triterpenes, two steroids, a coumarin, an acridone alkaloid, and a flavonoid glycoside. Their structures were established by comprehensive spectroscopic and spectrometric analyses (1D and 2D NMR, ESI-HR-MS) and by comparison with previously reported data. 13C NMR data of araliopsinine are also reported here for the first time. The isolated compounds were screened in vitro for their effects on the viability of two different human cancer cell lines, namely prostate PC-3 adenocarcinoma cells and colorectal HT-29 adenocarcinoma cells. However, none of the tested compounds exhibited strong anti-proliferative or cytotoxic activities, to either prostate PC-3 cells or colon HT-29 cells. At 100 μM, the furoquinoline maculine showed a slightly increased anti-proliferative effect, however, exclusively on HT-29 cells. The chemotaxonomic significance of the isolated compounds has also been discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 607
TI  - Phosphorylation‐dependent control of an RNA granule‐localized protein that fine‐tunes defence gene expression at a post‐transcriptional level
JO  - Plant J.
PY  - 2020
SP  - 1023-1039
AU  - Tabassum, N.
AU  - Eschen-Lippold, L.
AU  - Athmer, B.
AU  - Baruah, M.
AU  - Brode, M.
AU  - Maldonado-Bonilla, L. D.
AU  - Hoehenwarter, W.
AU  - Hause, G.
AU  - Scheel, D.
AU  - Lee, J.
AU  - 
VL  - 101
UR  - 
DO  - 10.1111/tpj.14573
AB  - Mitogen‐activated protein kinase (MAPK) cascades are key signalling modules of plant defence responses to pathogen‐associated molecular patterns (PAMPs, e.g. bacterial flg22 peptide). The Tandem Zinc Finger Protein 9 (TZF9) is an RNA‐binding protein that is phosphorylated by two PAMP‐responsive MAPKs, MPK3 and MPK6. We mapped the major phosphosites in TZF9 and showed their importance for controlling in vitro RNA‐binding activity, in vivo flg22‐induced rapid disappearance of TZF9‐labelled processing body‐like structures and TZF9 protein turnover. Microarray analysis showed a strong discordance between transcriptome (total mRNA) and translatome (polysome‐associated mRNA) in the tzf9 mutant, with more mRNAs associated to ribosomes in the absence of TZF9. This suggests that TZF9 may sequester and inhibit translation of subsets of mRNAs. Fittingly, TZF9 physically interacts with poly(A)‐binding protein 2 (PAB2), a hallmark constituent of stress granules – a site for stress‐induced translational stalling/arrest. TZF9 even promotes stress granule assembly in the absence of stress. Hence, MAPKs may control defence gene expression post‐transcriptionally through release from translation arrest within TZF9‐PAB2‐containing RNA granules or perturbing PAB2 functions in translation control (e.g. in the mRNA closed‐loop model of translation).
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 605
TI  - NFDI4Chem - Towards a National Research Data Infrastructure for Chemistry in Germany
JO  - Res. Ideas Outcomes
PY  - 2020
SP  - e55852
AU  - Steinbeck, C.
AU  - Koepler, O.
AU  - Bach, F.
AU  - Herres-Pawlis, S.
AU  - Jung, N.
AU  - Liermann, J. C.
AU  - Neumann, S.
AU  - Razum, M.
AU  - Baldauf, C.
AU  - Biedermann, F.
AU  - Bocklitz, T. W.
AU  - Boehm, F.
AU  - Broda, F.
AU  - Czodrowski, P.
AU  - Engel, T.
AU  - Hicks, M. G.
AU  - Kast, S. M.
AU  - Kettner, C.
AU  - Koch, W.
AU  - Lanza, G.
AU  - Link, A.
AU  - Mata, R. A.
AU  - Nagel, W. E.
AU  - Porzel, A.
AU  - Schlörer, N.
AU  - Schulze, T.
AU  - Weinig, H.-G.
AU  - Wenzel, W.
AU  - Wessjohann, L. A.
AU  - Wulle, S.
AU  - 
VL  - 6
UR  - 
DO  - 10.3897/rio.6.e55852
AB  - The vision of NFDI4Chem is the digitalisation of all key steps in chemical research to support scientists in their efforts to collect, store, process, analyse, disclose and re-use research data. Measures to promote Open Science and Research Data Management (RDM) in agreement with the FAIR data principles are fundamental aims of NFDI4Chem to serve the chemistry community with a holistic concept for access to research data. To this end, the overarching objective is the development and maintenance of a national research data infrastructure for the research domain of chemistry in Germany, and to enable innovative and easy to use services and novel scientific approaches based on re-use of research data. NFDI4Chem intends to represent all disciplines of chemistry in academia. We aim to collaborate closely with thematically related consortia. In the initial phase, NFDI4Chem focuses on data related to molecules and reactions including data for their experimental and theoretical characterisation.This overarching goal is achieved by working towards a number of key objectives:Key Objective 1: Establish a virtual environment of federated repositories for storing, disclosing, searching and re-using research data across distributed data sources. Connect existing data repositories and, based on a requirements analysis, establish domain-specific research data repositories for the national research community, and link them to international repositories.Key Objective 2: Initiate international community processes to establish minimum information (MI) standards for data and machine-readable metadata as well as open data standards in key areas of chemistry. Identify and recommend open data standards in key areas of chemistry, in order to support the FAIR principles for research data. Finally, develop standards, if there is a lack.Key Objective 3: Foster cultural and digital change towards Smart Laboratory Environments by promoting the use of digital tools in all stages of research and promote subsequent Research Data Management (RDM) at all levels of academia, beginning in undergraduate studies curricula.Key Objective 4: Engage with the chemistry community in Germany through a wide range of measures to create awareness for and foster the adoption of FAIR data management. Initiate processes to integrate RDM and data science into curricula. Offer a wide range of training opportunities for researchers.Key Objective 5: Explore synergies with other consortia and promote cross-cutting development within the NFDI.Key Objective 6: Provide a legally reliable framework of policies and guidelines for FAIR and open RDM.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 604
TI  - Vesicular ATP-binding cassette transporters in human disease: relevant aspects of their organization for future drug development
JO  - Future Drug Discovery
PY  - 2020
SP  - FDD51
AU  - Stefan, K.
AU  - Wen Leck, L. Y.
AU  - Namasivayam, V.
AU  - Bascuñana, P.
AU  - Huang, M. L.-H.
AU  - Riss, P. J.
AU  - Pahnke, J.
AU  - Jansson, P. J.
AU  - Stefan, S. M.
AU  - 
VL  - 4
UR  - 
DO  - 10.4155/fdd-2020-0025
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 603
TI  - PSYCHE—A Valuable Experiment in Plant NMR-Metabolomics
JO  - Molecules
PY  - 2020
SP  - 5125
AU  - Stark, P.
AU  - Zab, C.
AU  - Porzel, A.
AU  - Franke, K.
AU  - Rizzo, P.
AU  - Wessjohann, L. A.
AU  - 
VL  - 25
UR  - https://doi.org/10.3390/molecules25215125
DO  - 10.3390/molecules25215125
AB  - 1H-NMR is a very reproducible spectroscopic method and, therefore, a powerful tool for the metabolomic analysis of biological samples. However, due to the high complexity of natural samples, such as plant extracts, the evaluation of spectra is difficult because of signal overlap. The new NMR “Pure Shift” methods improve spectral resolution by suppressing homonuclear coupling and turning multiplets into singlets. The PSYCHE (Pure Shift yielded by Chirp excitation) and the Zangger–Sterk pulse sequence were tested. The parameters of the more suitable PSYCHE experiment were optimized, and the extracts of 21 Hypericum species were measured. Different evaluation criteria were used to compare the suitability of the PSYCHE experiment with conventional 1H-NMR. The relationship between the integral of a signal and the related bin value established by linear regression demonstrates an equal representation of the integrals in binned PSYCHE spectra compared to conventional 1H-NMR. Using multivariate data analysis based on both techniques reveals comparable results. The obtained data demonstrate that Pure Shift spectra can support the evaluation of conventional 1H-NMR experiments.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 602
TI  - Two isostructural Co(II) flufenamato and niflumato complexes with bathocuproine: Analogues with a different cytotoxic activity
JO  - J. Inorg. Biochem.
PY  - 2020
SP  - 111160
AU  - Smolko, L.
AU  - Smolková, R.
AU  - Samoľová, E.
AU  - Morgan, I.
AU  - Saoud, M.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 210
UR  - https://doi.org/10.1016/j.jinorgbio.2020.111160
DO  - 10.1016/j.jinorgbio.2020.111160
AB  - Two novel Co(II) fenamato complexes containing bathocuproine (bcp), namely [Co(bcp)(flu)2] (1) and [Co(bcp)(nif)2] (2) (flu = flufenamato, nif = niflumato) were synthesized and characterized by elemental analysis, single-crystal X-ray structure analysis as well as absorption and fluorescence spectroscopy. Investigation of their molecular structure revealed that both complexes are isostructural and form analogous complex molecules, with a Co(II) atom hexacoordinated by two nitrogen atoms of bcp and four oxygen atoms of two chelate bonded flu (1) and nif (2) ligands in a distorted octahedral arrangement. Surprisingly, the results of cytotoxicity experiments on four cancer cell lines (HeLa, HT-29, PC-3 and MCF-7) have revealed that despite similar structure of the complexes, the nif complex exhibits significantly higher activity, being the most effective against the PC-3 cell line (IC50 (MTT) = 6.11 ± 1.95 μM). Further studies performed on PC-3 cell line have shown that the mechanism of the cytotoxic action of nif complex (2) might involve activation of autophagic processes and apoptosis, while for its flu analogue (1) apoptosis was detected.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 601
TI  - Comparative analysis of the plastid conversion, photochemical activity and chlorophyll degradation in developing embryos of green-seeded and yellow-seeded pea (Pisum sativum) cultivars
JO  - Funct. Plant Biol.
PY  - 2020
SP  - 409-424
AU  - Smolikova, G.
AU  - Shiroglazova, O.
AU  - Vinogradova, G.
AU  - Leppyanen, I.
AU  - Dinastiya, E.
AU  - Yakovleva, O.
AU  - Dolgikh, E.
AU  - Titova, G.
AU  - Frolov, A.
AU  - Medvedev, S.
AU  - 
VL  - 47
UR  - 
DO  - 10.1071/FP19270
AB  - Developing seeds of some higher plants are photosynthetically active and contain chlorophylls (Chl), which are typically destroyed at the late stages of seed maturation. However, in some crop plant cultivars, degradation of embryonic Chl remains incomplete, and mature seeds preserve green colour, as it is known for green-seeded cultivars of pea (Pisum sativum L.). The residual Chl compromise seed quality and represent a severe challenge for farmers. Hence, comprehensive understanding of the molecular mechanisms, underlying incomplete Chl degradation is required for maintaining sustainable agriculture. Therefore, here we address dynamics of plastid conversion and photochemical activity alterations, accompanying degradation of Chl in embryos of yellow- and green-seeded cultivars Frisson and Rondo respectively. The yellow-seeded cultivar demonstrated higher rate of Chl degradation at later maturation stage, accompanied with termination of photochemical activity, seed dehydration and conversion of green plastids into amyloplasts. In agreement with this, expression of genes encoding enzymes of Chl degradation was lower in the green seeded cultivar, with the major differences in the levels of Chl b reductase (NYC1) and pheophytinase (PPH) transcripts. Thus, the difference between yellow and green seeds can be attributed to incomplete Chl degradation in the latter at the end of maturation period.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 600
TI  - Bringing new methods to the seed proteomics platform: Challenges and perspectives
JO  - Int. J. Mol. Sci.
PY  - 2020
SP  - 9162
AU  - Smolikova, G.
AU  - Gorbach, D.
AU  - Lukasheva, E.
AU  - Mavropolo-Stolyarenko, G.
AU  - Bilova, T.
AU  - Soboleva, A.
AU  - Tsarev, A.
AU  - Romanovskaya, E.
AU  - Podolskaya, E.
AU  - Zhukov, V. A.
AU  - Tikhonovich, I.
AU  - Medvedev, S.
AU  - Hoehenwarter, W.
AU  - Frolov, A.
AU  - 
VL  - 21
UR  - https://www.mdpi.com/1422-0067/21/23/9162
DO  - 10.3390/ijms21239162
AB  - For centuries, crop plants have represented the basis of the daily human diet. Among them, cereals and legumes, accumulating oils, proteins, and carbohydrates in their seeds, distinctly dominate modern agriculture, thus play an essential role in food industry and fuel production. Therefore, seeds of crop plants are intensively studied by food chemists, biologists, biochemists, and nutritional physiologists. Accordingly, seed development and germination as well as age- and stress-related alterations in seed vigor, longevity, nutritional value, and safety can be addressed by a broad panel of analytical, biochemical, and physiological methods. Currently, functional genomics is one of the most powerful tools, giving direct access to characteristic metabolic changes accompanying plant development, senescence, and response to biotic or abiotic stress. Among individual post-genomic methodological platforms, proteomics represents one of the most effective ones, giving access to cellular metabolism at the level of proteins. During the recent decades, multiple methodological advances were introduced in different branches of life science, although only some of them were established in seed proteomics so far. Therefore, here we discuss main methodological approaches already employed in seed proteomics, as well as those still waiting for implementation in this field of plant research, with a special emphasis on sample preparation, data acquisition, processing, and post-processing. Thereby, the overall goal of this review is to bring new methodologies emerging in different areas of proteomics research (clinical, food, ecological, microbial, and plant proteomics) to the broad society of seed biologists.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 599
TI  - Expanding the diversity of plant monoterpenoid indole alkaloids employing human cytochrome P450 3A4
JO  - ChemBioChem
PY  - 2020
SP  - 1976-1980
AU  - Sheludko, Y. V.
AU  - Volk, J.
AU  - Brandt, W.
AU  - Warzecha, H.
AU  - 
VL  - 21
UR  - 
DO  - 10.1002/cbic.202000020
AB  - Human drug‐metabolizing cytochrome P450 monooxygenases (CYPs) have enormous substrate promiscuity; this makes them promising tools for the expansion of natural product diversity. Here, we used CYP3A4 for the targeted diversification of a plant biosynthetic route leading to monoterpenoid indole alkaloids. In silico, in vitro and in planta studies proved that CYP3A4 was able to convert the indole alkaloid vinorine into vomilenine, the former being one of the central intermediates in the ajmaline pathway in the medicinal plant Rauvolfia serpentina  (L.) Benth. ex Kurz. However, to a much larger extent, the investigated conversion yielded vinorine (19R ,20R)‐epoxide, a new metabolite with an epoxide functional group that is rare for indole alkaloids. The described work represents a successful example of combinatorial biosynthesis towards an increase in biodiversity of natural metabolites. Moreover, characterisation of the products of the in vitro and in planta transformation of potential pharmaceuticals with human CYPs might be indicative of the route of their conversion in the human organism.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 598
TI  - Synthesis of new boswellic acid derivatives as potential antiproliferative agents
JO  - Nat. Prod. Res.
PY  - 2020
SP  - 1845-1852
AU  - Shamraiz, U.
AU  - Hussain, H.
AU  - Ur Rehman, N.
AU  - Al-Shidhani, S.
AU  - Saeed, A.
AU  - Khan, H. Y.
AU  - Khan, A.
AU  - Fischer, L.
AU  - Csuk, R.
AU  - Badshah, A.
AU  - Al-Rawahi, A.
AU  - Hussain, J.
AU  - Al-Harrasi, A.
AU  - 
VL  - 34
UR  - 
DO  - 10.1080/14786419.2018.1564295
AB  - In the current investigation, a series of heterocyclic derivatives of boswellic acids were prepared along with new monomers of 3-O-acetyl-11-keto-β-boswellic acid (AKBA, 1) 11-keto-β-boswellic acid (KBA, 2) and several new bis-AKBA and KBA homodimers and AKBA-KBA heterodimers. The effects of these compounds on the proliferation of different human cancer cell lines, viz., FaDu (pharynx carcinoma), A2780 (ovarian carcinoma), HT29 (colon adenocarcinoma), and A375 (malignant melanoma), have been evaluated. Thus, KBA homodimer 21 effectively inhibited the growth of FaDu, A2780, HT29, and A375 cells with EC50 values below 9 μM. In addition, compounds 7, 8, 11, 12, 15, 16, and 17 also exhibited cytotoxic effects for A2780, HT29, and A375 cancer cells. In particular, the pyrazine analog 8 was highly cytotoxic for A375 cancer cells with an EC50 value of 2.1 μM.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 592
TI  - A piperic acid CoA ligase produces a putative precursor of piperine, the pungent principle from black pepper fruits
JO  - Plant J.
PY  - 2020
SP  - 569-581
AU  - Schnabel, A.
AU  - Cotinguiba, F.
AU  - Athmer, B.
AU  - Yang, C.
AU  - Westermann, B.
AU  - Schaks, A.
AU  - Porzel, A.
AU  - Brandt, W.
AU  - Schumacher, F.
AU  - Vogt, T.
AU  - 
VL  - 102
UR  - 
DO  - 10.1111/tpj.14652
AB  - Black pepper (Piper nigrum L.) is known for the high content of piperine, a cinnamoyl amide derivative regarded as largely responsible for the pungent taste of this widely used spice. Despite its long history and worldwide use, the biosynthesis of piperine and related amides has been enigmatic up to now. In this report we describe a specific piperic acid CoA ligase from immature green fruits of P. nigrum. The corresponding enzyme was cloned and functionally expressed in E. coli. The recombinant enzyme displays a high specificity for piperic acid and does not accept the structurally related feruperic acid characterized by a similar C‐2 extension of the general C6‐C3 phenylpropanoid structure. The enzyme is also inactive with the standard set of hydroxycinnamic acids tested including caffeic acid, 4‐coumaric acid, ferulic acid, and sinapic acid. Substrate specificity is corroborated by in silico modeling which suggests a perfect fit of the substrate piperic acid to the active site of the piperic acid CoA ligase. The CoA ligase gene shows highest expression levels in immature green fruits, is also expressed in leaves and flowers, but not in roots. Virus‐induced gene silencing provided some preliminary indications that the production of piperoyl‐CoA is required for the biosynthesis of piperine in black pepper fruits.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 590
TI  - Improved Stability and Tunable Functionalization of Parallel β‐Sheets via Multicomponent N‐Alkylation of the Turn Moiety
JO  - Angew. Chem.
PY  - 2020
SP  - 265-269
AU  - Ricardo, M. G.
AU  - Moya, C. G.
AU  - Pérez, C. S.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - Rivera, D. G.
AU  - 
VL  - 132
UR  - 
DO  - 10.1002/ange.201912095
AB  - In contrast to the myriad of methods available to produce α‐helices and antiparallel β‐sheets in synthetic peptides, just a few are known for the construction of stable, non‐cyclic parallel β‐sheets. Herein, we report an efficient on‐resin approach for the assembly of parallel β‐sheet peptides in which the N‐alkylated turn moiety enhances the stability and gives access to a variety of functionalizations without modifying the parallel strands. The key synthetic step of this strategy is the multicomponent construction of an N‐alkylated turn using the Ugi reaction on varied isocyano‐resins. This four‐component process assembles the orthogonally protected turn fragment and incorporates handles serving for labeling/conjugation purposes or for reducing peptide aggregation. NMR and circular dichroism analyses confirm the better‐structured and more stable parallel β‐sheets in the N‐alkylated peptides compared to the non‐functionalized variants.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 589
TI  - Improved Stability and Tunable Functionalization of Parallel β-Sheets via Multicomponent N-Alkylation of the Turn Moiety
JO  - Angew. Chem. Int. Ed.
PY  - 2020
SP  - 259-263
AU  - Ricardo, M. G.
AU  - Moya, C. G.
AU  - Pérez, C. S.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - Rivera, D. G.
AU  - 
VL  - 59
UR  - 
DO  - 10.1002/anie.201912095
AB  - In contrast to the myriad of methods available to produce α‐helices and antiparallel β‐sheets in synthetic peptides, just a few are known for the construction of stable, non‐cyclic parallel β‐sheets. Herein, we report an efficient on‐resin approach for the assembly of parallel β‐sheet peptides in which the N‐alkylated turn moiety enhances the stability and gives access to a variety of functionalizations without modifying the parallel strands. The key synthetic step of this strategy is the multicomponent construction of an N‐alkylated turn using the Ugi reaction on varied isocyano‐resins. This four‐component process assembles the orthogonally protected turn fragment and incorporates handles serving for labeling/conjugation purposes or for reducing peptide aggregation. NMR and circular dichroism analyses confirm the better‐structured and more stable parallel β‐sheets in the N‐alkylated peptides compared to the non‐functionalized variants.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 588
TI  - Nutrient and Sensory Metabolites Profiling of Averrhoa Carambola L. (Starfruit) in the Context of Its Origin and Ripening Stage by GC/MS and Chemometric Analysis
JO  - Molecules
PY  - 2020
SP  - 2423
AU  - Ramadan, N. S.
AU  - Wessjohann, L. A.
AU  - Mocan, A.
AU  - Vodnar, D. C.
AU  - El-Sayed, N. H.
AU  - El-Toumy, S. A.
AU  - Mohamed, D. A.
AU  - Aziz, Z. A.
AU  - Ehrlich, A.
AU  - Farag, M. A.
AU  - 
VL  - 25
UR  - 
DO  - 10.3390/molecules25102423
AB  - Averrhoa carambola L. is a tropical tree with edible fruit that grows at different climatic conditions. Despite its nutritive value and reported health benefits, it is a controversial fruit owing to its rich oxalate content. The present study aimed at investigating aroma and nutrient primary metabolites distribution in A. carambola fruits grown in Indonesia, Malaysia (its endemic origin) versus Egypt, and at different ripening stages. Two techniques were employed to assess volatile and non-volatile metabolites including headspace solid-phase micro-extraction (HS-SPME) joined with gas chromatography coupled with mass-spectrometry (GC-MS) and GC-MS post silylation, respectively. Twenty-four volatiles were detected, with esters amounting for the major class of volatiles in Egyptian fruit at ca. 66%, with methyl caproate as the major component, distinguishing it from other origins. In contrast, aldehydes predominated tropically grown fruits with the ether myristicin found exclusively in these. Primary metabolites profiling led to the identification of 117 metabolites viz. sugars, polyols and organic acids. Fructose (38–48%) and glucose (21–25%) predominated sugar compositions in ripe fruits, whereas sorbitol was the major sugar alcohol (2.4–10.5%) in ripe fruits as well. Oxalic acid, an anti-nutrient with potential health risks, was the major organic acid detected in all the studied fruits (1.7–2.7%), except the Malaysian one (0.07%). It increases upon fruit ripening, including considerable amounts of volatile oxalate esters detected via SPME, and which must not be omitted in total oxalate determinations for safety assessments.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 587
TI  - Early Cognitive Training Rescues Remote Spatial Memory but Reduces Cognitive Flexibility in Alzheimer’s Disease Mice
JO  - J. Alzheimers Dis.
PY  - 2020
SP  - 1301-1317
AU  - Rai, S. P.
AU  - Krohn, M.
AU  - Pahnke, J.
AU  - 
VL  - 75
UR  - 
DO  - 10.3233/JAD-200161
AB  - Background:Spatial memory dysfunction has been demonstrated in mouse models of Alzheimer’s disease (AD) which is consistent with the clinical finding that the early signature of AD includes difficulties in the formation and/or storage of a memory. A stored memory—a long term memory—can be modulated via process called as memory retrieval that can either lead toward memory reconsolidation or even memory extinction.Objective:We aim to shed light on the fate of the spatial memory during memory reactivation and memory extinction using a water maze task.Methods:In Set-up I, we trained 3-month-old mice (wild-type mice and mice with cerebral β-amyloidosis) and assessed the fate of remote memory after four months of retention interval (RI). In Set-up II, we performed an early-extensive training at 2 months of age, retrained the same mice at 3 months of age, introduced four months of RI, and finally assessed remote spatial memory at 7 months of age.Results:We find in β-amyloidosis mice that memory reactivation problems were detectable at 7 months of age and were alleviated by cognitive overtraining. Similarly, forgetting of remote spatial memory was also minimized by cognitive overtraining. Finally, we show that the cognitive training facilitates the recovery of the reactivated spatial memory while reducing the ability to form new spatial memory in AD mice.Conclusion:This result may explain the rationality behind the cognitive reserve observed in AD patients and elderly with severe β-amyloidosis not corresponding to the actual low dementia symptoms.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 586
TI  - Detection and Prediction of Mild Cognitive Impairment in Alzheimer’s Disease Mice
JO  - J. Alzheimers Dis.
PY  - 2020
SP  - 1209-1221
AU  - Rai, S. P.
AU  - Bascuñana, P.
AU  - Brackhan, M.
AU  - Krohn, M.
AU  - Möhle, L.
AU  - Paarmann, K.
AU  - Pahnke, J.
AU  - 
VL  - 77
UR  - 
DO  - 10.3233/jad-200675
AB  - Background: The recent failure of clinical trials to treat Alzheimer’s disease (AD) indicates that the current approach of modifying disease is either wrong or is too late to be efficient. Mild cognitive impairment (MCI) denotes the phase between the preclinical phase and clinical overt dementia. AD mouse models that overexpress human amyloid-β (Aβ) are used to study disease pathogenesis and to conduct drug development/testing. However, there is no direct correlation between the Aβ deposition, the age of onset, and the severity of cognitive dysfunction. Objective: To detect and predict MCI when Aβ plaques start to appear in the hippocampus of an AD mouse. Methods: We trained wild-type and AD mice in a Morris water maze (WM) task with different inter-trial intervals (ITI) at 3 months of age and assessed their WM performance. Additionally, we used a classification algorithm to predict the genotype (APPtg versus wild-type) of an individual mouse from their respective WM data. Results: MCI can be empirically detected using a short-ITI protocol. We show that the ITI modulates the spatial learning of AD mice without affecting the formation of spatial memory. Finally, a simple classification algorithm such as logistic regression on WM data can give an accurate prediction of the cognitive dysfunction of a specific mouse. Conclusion: MCI can be detected as well as predicted simultaneously with the onset of Aβ deposition in the hippocampus in AD mouse model. The mild cognitive impairment prediction can be used for assessing the efficacy of a treatment.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 584
TI  - Synthesis, characterization and in vitro biological evaluation of novel organotin(IV) compounds with derivatives of 2-(5-arylidene-2,4-dioxothiazolidin-3-yl)propanoic acid
JO  - J. Inorg. Biochem.
PY  - 2020
SP  - 111207
AU  - Pantelić, N. ?.
AU  - Zmejkovski, B. B.
AU  - Božić, B.
AU  - Dojčinović, B.
AU  - Banjac, N. R.
AU  - Wessjohann, L. A.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 211
UR  - https://doi.org/10.1016/j.jinorgbio.2020.111207
DO  - 10.1016/j.jinorgbio.2020.111207
AB  - Two novel triphenyltin(IV) compounds, [Ph3SnL1] (L1 = 2-(5-(4-fluorobenzylidene)-2,4-dioxotetrahydrothiazole-3-yl)propanoate (1)) and [Ph3SnL2] (L2 = 2-(5-(5-methyl-2-furfurylidene)-2,4-dioxotetrahydrothiazole-3-yl)propanoate (2)) were synthesized and characterized by FT-IR, (1H and 13C) NMR spectroscopy, mass spectrometry, and elemental microanalysis. The in vitro anticancer activity of the synthesized organotin(IV) compounds was determined against four tumor cell lines: PC-3 (prostate), HT-29 (colon), MCF-7 (breast), and HepG2 (hepatic) using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystal violet) assays. The IC50 values are found to be in the range from 0.11 to 0.50 μM. Compound 1 exhibits the highest activity toward PC-3 cells (IC50 = 0.115 ± 0.009 μM; CV assay). The tin and platinum uptake in PC-3 cells showed a threefold lower uptake of tin in comparison to platinum (as cisplatin). Together with its higher activity this indicates a much higher cell inhibition potential of the tin compounds (calculated to ca. 50 to 100 times). Morphological analysis suggested that the compounds induce apoptosis in PC-3 cells, and flow cytometry analysis revealed that 1 and 2 induce autophagy as well as NO (nitric oxide) production.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 583
TI  - Sequestrate syndrome in Bondarzewia guaitecasensis (Fungi, Basidiomycota)? The case of Hybogaster giganteus revisited
JO  - Phytotaxa
PY  - 2020
SP  - 272-282
AU  - Palfner, G.
AU  - GALLEGUILLOS, F.
AU  - Arnold, N.
AU  - CASANOVA-KATNY, A.
AU  - HORAK, E.
AU  - 
VL  - 474
UR  - https://www.biotaxa.org/Phytotaxa/article/view/phytotaxa.474.3.6
DO  - 10.11646/phytotaxa.474.3.6
AB  - Based on comparison of molecular, morphological and ecological data, we propose that Hybogaster giganteus Singer, a parasitic basidiomycete on stem bases and coarse roots of Nothofagus in Chile, is conspecifically related to the sympatric Bondarzewia guaitecasensis. According to our concept, H. giganteus is representing a sequestrate form of the latter and is hence recombined and formally described as Bondarzewia guaitecasensis f. gigantea; we further discuss the evidence that its sequestrate morphology may provide higher resistance to drought stress in early autumn, extending the sporulation season of the species.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 624
TI  - Measurement of cerebral ABCC1 transport activity in wild-type and APP/PS1-21 mice with positron emission tomography
JO  - J. Cereb. Blood Flow Metab.
PY  - 2020
SP  - 954-965
AU  - Zoufal, V.
AU  - Mairinger, S.
AU  - Krohn, M.
AU  - Wanek, T.
AU  - Filip, T.
AU  - Sauberer, M.
AU  - Stanek, J.
AU  - Kuntner, C.
AU  - Pahnke, J.
AU  - Langer, O.
AU  - 
VL  - 40
UR  - 
DO  - 10.1177/0271678X19854541
AB  - Previous data suggest a possible link between multidrug resistance-associated protein 1 (ABCC1) and brain clearance of beta-amyloid (Aβ). We used PET with 6-bromo-7-[11C]methylpurine ([11C]BMP) to measure cerebral ABCC1 transport activity in a beta-amyloidosis mouse model (APP/PS1-21) and in wild-type mice aged 50 and 170 days, without and with pretreatment with the ABCC1 inhibitor MK571. One hundred seventy days-old-animals additionally underwent [11C]PiB PET scans to measure Aβ load. While baseline [11C]BMP PET scans detected no differences in the elimination slope of radioactivity washout from the brain (kelim) between APP/PS1-21 and wild-type mice of both age groups, PET scans after MK571 pretreatment revealed significantly higher kelim values in APP/PS1-21 mice than in wild-type mice aged 170 days, suggesting increased ABCC1 activity. The observed increase in kelim occurred across all investigated brain regions and was independent of the presence of Aβ plaques measured with [11C]PiB. Western blot analysis revealed a trend towards increased whole brain ABCC1 levels in 170 days-old-APP/PS1-21 mice versus wild-type mice and a significant positive correlation between ABCC1 levels and kelim. Our data point to an upregulation of ABCC1 in APP/PS1-21 mice, which may be related to an induction of ABCC1 in astrocytes as a protective mechanism against oxidative stress.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 191
TI  - Colombia hacia una sociedad 
del conocimiento. Reflexiones 
y propuestas
T2  - 
PB  - 
PY  - 2020
SP  - 1-450
AU  - Restrepo, S.
AU  - Samper, C.
AU  - di Palma, F.
AU  - Hodson, E.
AU  - Torres, M.
AU  - Reol, E. M.
AU  - Eddi, M.
AU  - Wessjohann, L.
AU  - Jaramillo, G. P.
AU  - et al., .
AU  - 
VL  - 
UR  - https://minciencias.gov.co/sites/default/files/upload/paginas/ebook-_colombia_hacia_una_sociedad_del_conocimiento.pdf
SN  - 978-958-5135-12-3
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 15
TI  - Insights into the Phytochemistry of the Cuban Endemic Medicinal Plant Phyllanthus orbicularis: Fideloside, a Novel Bioactive 8-C-glycosyl 2,3-Dihydroflavonol
T2  - Natural Products and Drug Discovery
PB  - Molecules
PY  - 2020
SP  - 79-92
AU  - Francioso, A.
AU  - Franke, K.
AU  - Villani, C.
AU  - Mosca, L.
AU  - d’Erme, M.
AU  - Frischbutter, S.
AU  - Brandt, W.
AU  - Sanchez-Lamar, A.
AU  - Wessjohann, L.
AU  - 
VL  - 
UR  - https://doi/103390./books978-3-03928-747-5
SN  - 978-3-03928-746-8
DO  - 10.3390/books978-3-03928-747-5
AB  - Phyllanthus orbicularis (Phyllanthaceae) is an endemic evergreen tropical plant of Cuba that grows in the western part of the island and is used in traditional medicine as an infusion. The aqueous extract of this plant presents a wide range of pharmacological activitiessuch as antimutagenic, antioxidant and antiviral effects. Given the many beneficial effects and the great interest in the development of new pharmacological products from natural sources, the aim of this work was to investigate the phytochemistry of this species and to elucidate the structure of the main bioactive principles. Besides thepresence of several known polyphenols, the major constituent was hitherto not described. The chemical structure of this compound, here named Fideloside, was elucidated by means of HR-ESIMS/MSn, 1D/2D NMR, FT-IR, and ECD as (2R,3R)-(−)-3’,4 ,5,7-tetrahydroxydihydroflavonol-8-C- -D-glucopyranoside. The compound, as well as the plant aqueous preparations, showed promising bioactive properties, i.e., anti-inflammatory capacity in human explanted monocytes, corroborating future pharmacological use for this new natural C-glycosyl flavanonol.
A2  - Pinarosa Avato
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 14
TI  - Antagonistic Microorganisms in Plant Protection: Consumers’ Friends or Foes?
T2  - 
PB  - Modern Fungicides and Antifungal Compounds
PY  - 2020
SP  - 217-228
AU  - Deising, H. B.
AU  - Amorim, R.
AU  - De Oliveira Silva, A.
AU  - Raschke, A.
AU  - Eisermann, I.
AU  - Wirsel, S. G. R.
AU  - Csuk, R.
AU  - Schmitz, L. M.
AU  - Arnold, N.
AU  - 
VL  - IX
UR  - https://plant-protection.net/de/publikationen/spectrum-phytomedizin
AB  - 
A2  - Deising, H. B. et al., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 13
TI  - Azadirachta indica: the medicinal properties of the global problems-solving tree
T2  - Biodiversity and Biomedicine
PB  - 
PY  - 2020
SP  - 305-316
AU  - Abbas, G.
AU  - Ali, M.
AU  - Hamaed, A.
AU  - Al-Sibani, M.
AU  - Hussain, H.
AU  - Al-Harrasi, A.
AU  - 
VL  - 
UR  - 
SN  - 9780128223703
DO  - 10.1016/B978-0-12-819541-3.00017-7
AB  - The Azadirachta indica, which is commonly known as the neem tree, has gained prominence thanks to its wide spectrum of medicinal properties and its great potential to treat various diseases. In 1992 the US National Academy of Sciences recognized the importance of this plant and declared neem as a tree for solving global problems. The A. indica belongs to the family Meliaceae. It is a fast growing tropical evergreen tree indigenous to the Indo-Pakistan subcontinent since antiquity. The A. indica is also known as a wonder tree due to its richness in bioactive components in all parts of the tree such as the leaves, the bark, the flowers, the fruits, the seeds, the roots, and the gum oil and therefore it is highly exploitable. Over the years, a large number of diverse types of chemical constituents belonging to the various classes of compounds such as flavonoids, alkaloids, triterpenoids, steroids, carotenoids, and ketones, as well as phenolic compounds, have been extracted from the neem plant. The ultimate goal is to promote plant-derived products with the least side effects as modern drugs. In the last few decades, apart from the chemical analysis of the neem compounds, many researchers have investigated the potential of natural products as candidate medications for the treatment of various diseases. As a summary, substantial progress has been made in identifying neem-derived bioactive compounds for the development of medications for the treatment of a wide range of diseases. In this chapter, the major bioactive components of A. indica are presented along with their applications for the cure of many life-threatening diseases.
A2  - Ozturk, M. et al., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2526
TI  - A cytochrome P450 from juvenile mustard leaf beetles hydroxylates geraniol, a key step in iridoid biosynthesis
JO  - bioRxiv
PY  - 2019
SP  - 
AU  - Fu, N.
AU  - Yang, Z.-l.
AU  - Pauchet, Y.
AU  - Paetz, C.
AU  - Brandt, W.
AU  - Boland, W.
AU  - Burse, A.
AU  - 
VL  - 
UR  - 
DO  - 10.1101/634485
AB  - Juveniles of the leaf beetle Phaedon cochleariae synthesize iridoid via the mevalonate pathway to repel predators. The normal terpenoid biosynthesis is integrated into the dedicated defensive pathway by the ω-hydroxylation of geraniol to 8-hydroxygeraniol. Here we identify and characterize the geraniol 8-hydroxylase as a P450 monooxygenase using integrated transcriptomic and proteomic analyses. In the fat body, 73 individual cytochrome P450s were identified. The double stranded RNA (dsRNA)-mediated knock down of CYP6BH5 led to a significant reduction of 8-hydroxygeraniol-glucoside in the hemolymph and, later, of the chrysomelidial in the defensive secretion. Heterologously expressed CYP6BH5 converted geraniol to 8-hydroxygeraniol. In addition to geraniol, CYP6BH5 also catalyzes other monoterpenols, such as nerol and citronellol, into the corresponding α, ω-dihydroxy compounds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 754
TI  - Influence of Multidrug Resistance-Associated Proteins on the Excretion of the ABCC1 Imaging Probe 6-Bromo-7-[11C]Methylpurine in Mice
JO  - Mol. Imaging Biol.
PY  - 2019
SP  - 306-316
AU  - Zoufal, V.
AU  - Mairinger, S.
AU  - Krohn, M.
AU  - Wanek, T.
AU  - Filip, T.
AU  - Sauberer, M.
AU  - Stanek, J.
AU  - Traxl, A.
AU  - Schuetz, J. D.
AU  - Kuntner, C.
AU  - Pahnke, J.
AU  - Langer, O.
AU  - 
VL  - 21
UR  - 
DO  - 10.1007/s11307-018-1230-y
AB  - PurposeMultidrug resistance-associated proteins (MRPs) mediate the hepatobiliary and renal excretion of many drugs and drug conjugates. The positron emission tomography (PET) tracer 6-bromo-7-[11C]methylpurine is rapidly converted in tissues by glutathione-S-transferases into its glutathione conjugate, and has been used to measure the activity of Abcc1 in the brain and the lungs of mice. Aim of this work was to investigate if the activity of MRPs in excretory organs can be measured with 6-bromo-7-[11C]methylpurine.ProceduresWe performed PET scans with 6-bromo-7-[11C]methylpurine in groups of wild-type, Abcc4(−/−) and Abcc1(−/−) mice, with and without pre-treatment with the prototypical MRP inhibitor MK571.Results6-Bromo-7-[11C]methylpurine-derived radioactivity predominantly underwent renal excretion. In blood, MK571 treatment led to a significant increase in the AUC and a decrease in the elimination rate constant of radioactivity (kelimination,blood). In the kidneys, there were significant decreases in the rate constant for radioactivity uptake from the blood (kuptake,kidney), kelimination,kidney, and the rate constant for tubular secretion of radioactivity (kurine). Experiments in Abcc4(−/−) mice indicated that Abcc4 contributed to renal excretion of 6-bromo-7-[11C]methylpurine-derived radioactivity.ConclusionsOur data suggest that 6-bromo-7-[11C]methylpurine may be useful to assess the activity of MRPs in the kidneys as well as in other organs (brain, lungs), although further work is needed to identify the MRP subtypes involved in the disposition of 6-bromo-7-[11C]methylpurine-derived radioactivity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 752
TI  - Medicago TERPENE SYNTHASE 10 Is Involved in Defense Against an Oomycete Root Pathogen
JO  - Plant Physiol.
PY  - 2019
SP  - 1598-1613
AU  - Yadav, H.
AU  - Dreher, D.
AU  - Athmer, B.
AU  - Porzel, A.
AU  - Gavrin, A.
AU  - Baldermann, S.
AU  - Tissier, A.
AU  - Hause, B.
AU  - 
VL  - 180
UR  - 
DO  - 10.1104/pp.19.00278
AB  - In nature, plants interact with numerous beneficial or pathogenic soil-borne microorganisms. Plants have developed various defense strategies to expel pathogenic microbes, some of which function soon after pathogen infection. We used Medicago truncatula and its oomycete pathogen Aphanomyces euteiches to elucidate early responses of the infected root. A. euteiches causes root rot disease in legumes and is a limiting factor in legume production. Transcript profiling of seedlings and adult plant roots inoculated with A. euteiches zoospores for 2 h revealed specific upregulation of a gene encoding a putative sesquiterpene synthase (M. truncatula TERPENE SYNTHASE 10 [MtTPS10]) in both developmental stages. MtTPS10 was specifically expressed in roots upon oomycete infection. Heterologous expression of MtTPS10 in yeast led to production of a blend of sesquiterpenes and sesquiterpene alcohols, with NMR identifying a major peak corresponding to himalachol. Moreover, plants carrying a tobacco (Nicotiana tabacum) retrotransposon Tnt1 insertion in MtTPS10 lacked the emission of sesquiterpenes upon A. euteiches infection, supporting the assumption that the identified gene encodes a multiproduct sesquiterpene synthase. Mttps10 plants and plants with reduced MtTPS10 transcript levels created by expression of an MtTPS10-artificial microRNA in roots were more susceptible to A. euteiches infection than were the corresponding wild-type plants and roots transformed with the empty vector, respectively. Sesquiterpenes produced by expression of MtTPS10 in yeast also inhibited mycelial growth and A. euteiches zoospore germination. These data suggest that sesquiterpene production in roots by MtTPS10 plays a previously unrecognized role in the defense response of M. truncatula against A. euteiches.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 750
TI  - pH effects on plant calcium fluxes: lessons from acidification-mediated calcium elevation induced by the γ-glutamyl-leucine dipeptide identified from Phytophthora infestans
JO  - Sci. Rep.
PY  - 2019
SP  - 4733
AU  - Westphal, L.
AU  - Strehmel, N.
AU  - Eschen-Lippold, L.
AU  - Bauer, N.
AU  - Westermann, B.
AU  - Rosahl, S.
AU  - Scheel, D.
AU  - Lee, J.
AU  - 
VL  - 9
UR  - 
DO  - 10.1038/s41598-019-41276-0
AB  - Cytosolic Ca2+ ([Ca2+]cyt) elevation is an early signaling response upon exposure to pathogen-derived molecules (so-called microbe-associated molecular patterns, MAMPs) and has been successfully used as a quantitative read-out in genetic screens to identify MAMP receptors or their associated components. Here, we isolated and identified by mass spectrometry the dipeptide γ-Glu-Leu as a component of a Phytophthora infestans mycelium extract that induces [Ca2+]cyt elevation. Treatment of Arabidopsis seedlings with synthetic γ-Glu-Leu revealed stimulatory effects on defense signaling, including a weak enhancement of the expression of some MAMP-inducible genes or affecting the refractory period to a second MAMP elicitation. However, γ-Glu-Leu is not a classical MAMP since pH adjustment abolished these activities and importantly, the observed effects of γ-Glu-Leu could be recapitulated by mimicking extracellular acidification. Thus, although γ-Glu-Leu can act as a direct agonist of calcium sensing receptors in animal systems, the Ca2+-mobilizing activity in plants reported here is due to acidification. Low pH also shapes the Ca2+ signature of well-studied MAMPs (e.g. flg22) or excitatory amino acids such as glutamate. Overall, this work serves as a cautionary reminder that in defense signaling studies where Ca2+ flux measurements are concerned, it is important to monitor and consider the effects of pH.
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions
ER  - 


TY  - JOUR
ID  - 742
TI  - A Multicomponent Stapling Approach to Exocyclic Functionalized Helical Peptides: Adding Lipids, Sugar, PEGs, Labels and Handles to the Lactam Bridge
JO  - Bioconjugate Chem.
PY  - 2019
SP  - 253-259
AU  - Vasco, A. V.
AU  - Méndez, Y.
AU  - Porzel, A.
AU  - Balbach, J.
AU  - Wessjohann, L. A.
AU  - Rivera, D. G.
AU  - 
VL  - 30
UR  - 
DO  - 10.1021/acs.bioconjchem.8b00906
AB  - Peptide stapling is traditionally used to lock peptide conformations into α-helical structures using a variety of macrocyclization chemistries. In an endeavor to add a diversity-generating tool to this repertoire, we introduce a multicomponent stapling approach enabling the simultaneous stabilization of helical secondary structures and the exocyclic N-functionalization of the side chain-tethering lactam bridge. This is accomplished by means of a novel solid-phase methodology comprising, for the first time, the on-resin Ugi reaction-based macrocyclization of peptide side chains bearing amino and carboxylic acid groups. The exocyclic diversity elements arise from the isocyanide component used in the Ugi multicomponent stapling protocol, which allows for the incorporation of relevant fragments such as lipids, sugars, polyethylene glycol, fluorescent labels, and reactive handles. We prove the utility of such exocyclic reactive groups in the bioconjugation of a maleimide-armed lactam-bridged peptide to a carrier protein. The on-resin multicomponent stapling proved efficient for the installation of not only one, but also two consecutive lactam bridges having either identical or dissimilar N-functionalities. The easy access to helical peptides with a diverse set of exocyclic functionalities shows prospect for applications in peptide drug discovery and chemical biology.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 741
TI  - Exposure to UV-B Radiation Leads to Increased Deposition of Cell Wall-Associated Xerocomic Acid in Cultures of Serpula himantioides
JO  - Appl. Environ. Microbiol.
PY  - 2019
SP  - e00870-19
AU  - Torres, S.
AU  - González-Ramírez, M.
AU  - Gavilán, J.
AU  - Paz, C.
AU  - Palfner, G.
AU  - Arnold, N.
AU  - Fuentealba, J.
AU  - Becerra, J.
AU  - Pérez, C.
AU  - Cabrera-Pardo, J. R.
AU  - 
VL  - 85
UR  - 
DO  - 10.1128/AEM.00870-19
AB  - Many fungi are thought to have developed morphological and physiological adaptations to cope with exposure to UV-B radiation, but in most species, such responses and their protective effects have not been explored. Here, we study the adaptive response to UV-B radiation in the widespread, saprotrophic fungus Serpula himantioides, frequently found colonizing coniferous wood in nature. We report the morphological and chemical responses of S. himantioides to controlled intensities of UV-B radiation, under in vitro culture conditions. Ultraviolet radiation induced a decrease in the growth rate of S. himantioides but did not cause gross morphological changes. Instead, we observed accumulation of pigments near the cell wall with increasing intensities of UV-B radiation. Nuclear magnetic resonance (NMR) and high-performance liquid chromatography-mass spectrometry (HPLC-MS) analyses revealed that xerocomic acid was the main pigment present, both before and after UV-B exposure, increasing from 7 mg/liter to 15 mg/liter after exposure. We show that xerocomic acid is a photoprotective metabolite with strong antioxidant abilities, as evidenced by DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt], and oxygen radical absorbance capacity (ORAC) assays. Finally, we assessed the capacity of xerocomic acid as a photoprotective agent on HEK293 cells and observed better photoprotective properties than those of β-carotene. Xerocomic acid is therefore a promising natural product for development as a UV-protective ingredient in cosmetic and pharmaceutical products.IMPORTANCE Our study shows the morphological and chemical responses of S. himantioides to controlled doses of UV-B radiation under in vitro culture conditions. We found that increased biosynthesis of xerocomic acid was the main strategy adopted by S. himantioides against UV-B radiation. Xerocomic acid showed strong antioxidant and photoprotective abilities, which has not previously been reported. Our results indicate that upon UV-B exposure, S. himantioides decreases its hyphal growth rate and uses this energy instead to increase the biosynthesis of xerocomic acid, which is allocated near the cell wall. This metabolic switch likely allows xerocomic acid to efficiently defend S. himantioides from UV radiation through its antioxidant and photoprotective properties. The findings further suggest that xerocomic acid is a promising candidate for development as a cosmetic ingredient to protect against UV radiation and should therefore be investigated in depth in the near future both in vitro and in vivo.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 739
TI  - Multiple Glycation Sites in Blood Plasma Proteins as an Integrated Biomarker of Type 2 Diabetes Mellitus
JO  - Int. J. Mol. Sci.
PY  - 2019
SP  - 2329
AU  - Soboleva, A.
AU  - Mavropulo-Stolyarenko, G.
AU  - Karonova, T.
AU  - Thieme, D.
AU  - Hoehenwarter, W.
AU  - Ihling, C.
AU  - Stefanov, V.
AU  - Grishina, T.
AU  - Frolov, A.
AU  - 
VL  - 20
UR  - 
DO  - 10.3390/ijms20092329
AB  - Type 2 diabetes mellitus (T2DM) is one of the most widely spread metabolic diseases. Because of its asymptomatic onset and slow development, early diagnosis and adequate glycaemic control are the prerequisites for successful T2DM therapy. In this context, individual amino acid residues might be sensitive indicators of alterations in blood glycation levels. Moreover, due to a large variation in the half-life times of plasma proteins, a generalized biomarker, based on multiple glycation sites, might provide comprehensive control of the glycemic status across any desired time span. Therefore, here, we address the patterns of glycation sites in highly-abundant blood plasma proteins of T2DM patients and corresponding age- and gender-matched controls by comprehensive liquid chromatography-mass spectrometry (LC-MS). The analysis revealed 42 lysyl residues, significantly upregulated under hyperglycemic conditions. Thereby, for 32 glycation sites, biomarker behavior was demonstrated here for the first time. The differentially glycated lysines represented nine plasma proteins with half-lives from 2 to 21 days, giving access to an integrated biomarker based on multiple protein-specific Amadori peptides. The validation of this biomarker relied on linear discriminant analysis (LDA) with random sub-sampling of the training set and leave-one-out cross-validation (LOOCV), which resulted in an accuracy, specificity, and sensitivity of 92%, 100%, and 85%, respectively.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 738
TI  - Glycation of Plant Proteins: Regulatory Roles and Interplay with Sugar Signalling?
JO  - Int. J. Mol. Sci.
PY  - 2019
SP  - 2366
AU  - Shumilina, J.
AU  - Kusnetsova, A.
AU  - Tsarev, A.
AU  - Janse van Rensburg, H. C.
AU  - Medvedev, S.
AU  - Demidchik, V.
AU  - Van den Ende, W.
AU  - Frolov, A.
AU  - 
VL  - 20
UR  - 
DO  - 10.3390/ijms20092366
AB  - Glycation can be defined as an array of non-enzymatic post-translational modifications of proteins formed by their interaction with reducing carbohydrates and carbonyl products of their degradation. Initial steps of this process rely on reducing sugars and result in the formation of early glycation products—Amadori and Heyns compounds via Schiff base intermediates, whereas their oxidative degradation or reactions of proteins with α-dicarbonyl compounds yield a heterogeneous group of advanced glycation end products (AGEs). These compounds accompany thermal processing of protein-containing foods and are known to impact on ageing, pathogenesis of diabetes mellitus and Alzheimer’s disease in mammals. Surprisingly, despite high tissue carbohydrate contents, glycation of plant proteins was addressed only recently and its physiological role in plants is still not understood. Therefore, here we summarize and critically discuss the first steps done in the field of plant protein glycation during the last decade. We consider the main features of plant glycated proteome and discuss them in the context of characteristic metabolic background. Further, we address the possible role of protein glycation in plants and consider its probable contribution to protein degradation, methylglyoxal and sugar signalling, as well as interplay with antioxidant defense.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 737
TI  - α-glucosidase inhibition (antidiabetic) of rubidium doped indium sulfide nanomaterials
JO  - Mater. Res. Express
PY  - 2019
SP  - 115051
AU  - Shamraiz, U.
AU  - Ahmad, Z.
AU  - Badshah, A.
AU  - Hussain, H.
AU  - Abbas, G.
AU  - Ullah, S.
AU  - Raza, B.
AU  - 
VL  - 6
UR  - 
DO  - 10.1088/2053-1591/ab4766
AB  - Herein, we report the In2S3 and rubidium doped In2S3 (Rb- In2S3) nanostructures and elucidate their role in α-glucosidase inhibition (AIGs). The phase, crystal structure, morphology, and composition of the as prepared In2S3 and Rb- In2S3 nanostructures was characterized by PXRD, SEM, TEM and EDS analysis, respectively. Pure In2S3 were unable to impart significance glucosidase inhibition activity, while the activity was remarkably enhanced with the doping of 5% Rb. The mass percentage of Rb (0.42 μg ml−1) is much lower than the transition metals-based drugs reported in the literature.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 736
TI  - Gold nanotubes and nanorings: promising candidates for multidisciplinary fields
JO  - Int. Mater. Rev.
PY  - 2019
SP  - 478-512
AU  - Shamraiz, U.
AU  - Raza, B.
AU  - Hussain, H.
AU  - Badshah, A.
AU  - Green, I. R.
AU  - Kiani, F. A.
AU  - Al-Harrasi, A.
AU  - 
VL  - 64
UR  - 
DO  - 10.1080/09506608.2018.1554991
AB  - Gold is considered as an inert metal and ranks as one of the noblest among all the metals. Progressive importance associated with nanotechnology offers potential development of new methods and controlled morphologies of the anisotropic gold nanostructures to develop its innovative properties and commensurate applications. The unique gold nanostructures are considered for their potential applications in various fields due to their large surface area, excellent adhesion properties and resistance to corrosion. In this review, we will present recent developments for gold nanorings and nanotubes, under the headings of synthesis, properties and potential applications in various fields.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 735
TI  - Synthesis and biochemical studies of novel organic selenides with increased selectivity for hepatocellular carcinoma and breast adenocarcinoma
JO  - Eur. J. Med. Chem.
PY  - 2019
SP  - 515-526
AU  - Shaaban, S.
AU  - Ashmawy, A. M.
AU  - Negm, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 179
UR  - 
DO  - 10.1016/j.ejmech.2019.06.075
AB  - Nineteen organoselenides were synthesized and tested for their intrinsic cytotoxicity in hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines and their corresponding selective cytotoxicity (SI) was estimated using normal lung fibroblast (WI-38) cells. Most of the organic selenides exhibited good anticancer activity, and this was more pronounced in HepG2 cells. Interestingly, the naphthoquinone- (5), thiazol- (12), and the azo-based (13) organic selenides demonstrated promising SI (up to 76). Furthermore, the amine 4c, naphthoquinone 5, and azo-based 13 and 15 organic selenides were able to down-regulate the expression of Bcl-2 and up-regulate the expression levels of IL-2, IL-6 and CD40 in HepG2 cells compared to untreated cells. Moreover, most of the synthesized candidates manifested good free radical-scavenging and GPx-like activities comparable to vitamin C and ebselen. The obtained results suggested that some of the presented organoselenium candidates have promising anti-HepG2 and antioxidant activities.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 733
TI  - Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH2 Core and Evaluation of Their Anticancer Activity
JO  - Pharmaceutics
PY  - 2019
SP  - 59
AU  - Seixas, N.
AU  - Ravanello, B. B.
AU  - Morgan, I.
AU  - Kaluđerović, G. N.
AU  - Wessjohann, L. A.
AU  - 
VL  - 11
UR  - 
DO  - 10.3390/pharmaceutics11020059
AB  - Herein, a new Ugi multicomponent reaction strategy is described to enhance activity and solubility of the chemotherapeutic drug chlorambucil through its conjugation to poly(amidoamine) (PAMAM-NH2) dendrimers with the simultaneous introduction of lipidic (i-Pr) and cationic (–NH2) or anionic (–COOH) groups. Standard viability assays were used to evaluate the anticancer potential of the water-soluble dendrimers against PC-3 prostate and HT-29 colon cancer cell lines, as well as non-cancerous mouse NIH3T3 fibroblasts. It could be demonstrated that the anticancer activity against PC-3 cells was considerably improved when both chlorambucil and –NH2 (cationic) groups were present on the dendrimer surface (1b). Additionally, this dendrimer showed activity only against the prostate cancer cells (PC-3), while it did not affect colon cancer cells and fibroblasts significantly. The cationic chlorambucil-dendrimer 1b blocks PC-3 cells in the G2/M phase and induces caspase independent apoptosis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 725
TI  - Metabolites profiling of Ziziphus leaf taxa via UHPLC/PDA/ESI-MS in relation to their biological activities
JO  - Food Chem.
PY  - 2019
SP  - 233-246
AU  - Sakna, S. T.
AU  - Mocan, A.
AU  - Sultani, H. N.
AU  - El-fiky, N. M.
AU  - Wessjohann, L. A.
AU  - Farag, M. A.
AU  - 
VL  - 293
UR  - 
DO  - 10.1016/j.foodchem.2019.04.097
AB  - Ziziphus plants are well recognized for their nutritive and medicinal value worldwide, albeit their chemical profile has yet to be fully reported. The secondary metabolites profile of three traditionally used Ziziphus leaf accessions was investigated via ultra-high performance liquid chromatography coupled to photodiode array and electrospray ionization mass detectors (UHPLC/PDA/ESI-MS). A total of 102 metabolites were characterized revealing the first holistic approach onto Ziziphus leaf metabolome and to include the first report of several novel flavonoids and cyclopeptide alkaloids. Fragmentation pattern for cyclopeptide alkaloids was proposed via ESI-MS. Principal component analysis (PCA) revealed close metabolite resemblance among Z. spina-christi and Z. mauritiana leaf specimens found enriched in saponins and distinct from that of Z. jujuba in which quercetin-3-O-(2-pentosyl)-rhamnoside was most abundant. Further, in-vitro antioxidant, anti-inflammatory and antidiabetic assays revealed for Z. spina-christi and Z. mauritiana strong effects compared to Z. jujuba and in correlation with their metabolites repertoire.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 721
TI  - Discovery of key regulators of dark glands development and hypericin biosynthesis in St. John&#39;s wort (Hypericum perforatum)
JO  - Plant Biotechnol. J.
PY  - 2019
SP  - 2299-2312
AU  - Rizzo, P.
AU  - Altschmied, L.
AU  - Stark, P.
AU  - Rutten, T.
AU  - Gündel, A.
AU  - Scharfenberg, S.
AU  - Franke, K.
AU  - Bäumlein, H.
AU  - Wessjohann, L.
AU  - Koch, M.
AU  - Borisjuk, L.
AU  - Sharbel, T. F.
AU  - 
VL  - 17
UR  - 
DO  - 10.1111/pbi.13141
AB  - Hypericin is a molecule of high pharmaceutical importance that is synthesized and stored in dark glands (DGs) of St. John&#39;s wort (Hypericum perforatum). Understanding which genes are involved in dark gland development and hypericin biosynthesis is important for the development of new Hypericum extracts that are highly demanded for medical applications. We identified two transcription factors, whose expression is strictly synchronized with the differentiation of DGs. We correlated the content of hypericin, pseudohypericin, endocrocin, skyrin glycosides and several flavonoids with gene expression and DG development to obtain a revised model for hypericin biosynthesis. Here we report for the first‐time genotypes which are polymorphic for the presence/total‐absence (G+/G‐) of DGs in their placental tissues (PTs). DG development was characterized in PTs using several microscopy techniques. Fourier‐transformed infrared microscopy was established as a novel method to precisely locate polyaromatic compounds, such as hypericin, in plant tissues. In addition, we obtained transcriptome and metabolome profiles of unprecedented resolution in Hypericum. This study addresses for the first time the development of dark glands and identifies genes that constitute strong building blocks for the further elucidation of hypericin synthesis, its manipulation in plants, its engineering in microbial systems, and its applications in medical research.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 719
TI  - Stabilization of Cyclic β-Hairpins by Ugi-Reaction-Derived N-Alkylated Peptides: The Quest for Functionalized β-Turns
JO  - Org. Lett.
PY  - 2019
SP  - 7307-7310
AU  - Ricardo, M. G.
AU  - Vasco, A. V.
AU  - Rivera, D. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 21
UR  - 
DO  - 10.1021/acs.orglett.9b02592
AB  - A solid-phase approach including on-resin Ugi reactions was developed for the construction of β-hairpins. Various N-alkylated dipeptide fragments proved capable of aligning antiparallel β-sheets in a macrocyclic scaffold, thus serving as β-hairpin templates. Gramicidin S was used as the model β-hairpin to compare the Ugi-derived β-turns with the type-II′ β-turn. The results show that the multicomponent incorporation of such N-alkylated residues allows for the simultaneous stabilization and exo-cyclic functionalization of cyclic β-hairpins.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 718
TI  - Introducing the Petasis Reaction for Late-Stage Multicomponent Diversification, Labeling, and Stapling of Peptides
JO  - Angew. Chem. Int. Ed.
PY  - 2019
SP  - 2700-2704
AU  - Ricardo, M. G.
AU  - Llanes, D.
AU  - Wessjohann, L. A.
AU  - Rivera, D. G.
AU  - 
VL  - 58
UR  - 
DO  - 10.1002/anie.201812620
AB  - For the first time, the Petasis (borono‐Mannich) reaction is employed for the multicomponent labeling and stapling of peptides. The report includes the solid‐phase derivatization of peptides at the N‐terminus, Lys, and Nϵ‐MeLys side‐chains by an on‐resin Petasis reaction with variation of the carbonyl and boronic acid components. Peptides were simultaneously functionalized with aryl/vinyl substituents bearing fluorescent/affinity tags and oxo components such as dihydroxyacetone, glyceraldehyde, glyoxylic acid, and aldoses, thus encompassing a powerful complexity‐generating approach without changing the charge of the peptides. The multicomponent stapling was conducted in solution by linking Nϵ‐MeLys or Orn side‐chains, positioned at i, i+7 and i, i+4, with aryl tethers, while hydroxy carbonyl moieties were introduced as exocyclic fragments. The good efficiency and diversity oriented character of these methods show prospects for peptide drug discovery and chemical biology.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 717
TI  - Introducing the Petasis Reaction for Late-Stage Multicomponent Diversification, Labeling, and Stapling of Peptides
JO  - Angew. Chem.
PY  - 2019
SP  - 2726-2730
AU  - Ricardo, M. G.
AU  - Llanes, D.
AU  - Wessjohann, L. A.
AU  - Rivera, D. G.
AU  - 
VL  - 131
UR  - 
DO  - 10.1002/ange.201812620
AB  - For the first time, the Petasis (borono‐Mannich) reaction is employed for the multicomponent labeling and stapling of peptides. The report includes the solid‐phase derivatization of peptides at the N‐terminus, Lys, and Nϵ‐MeLys side‐chains by an on‐resin Petasis reaction with variation of the carbonyl and boronic acid components. Peptides were simultaneously functionalized with aryl/vinyl substituents bearing fluorescent/affinity tags and oxo components such as dihydroxyacetone, glyceraldehyde, glyoxylic acid, and aldoses, thus encompassing a powerful complexity‐generating approach without changing the charge of the peptides. The multicomponent stapling was conducted in solution by linking Nϵ‐MeLys or Orn side‐chains, positioned at i, i+7 and i, i+4, with aryl tethers, while hydroxy carbonyl moieties were introduced as exocyclic fragments. The good efficiency and diversity oriented character of these methods show prospects for peptide drug discovery and chemical biology.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 716
TI  - A Peptide Backbone Stapling Strategy Enabled by the Multicomponent Incorporation of Amide N‐Substituents
JO  - Chem.-Eur. J.
PY  - 2019
SP  - 769-774
AU  - Ricardo, M. G.
AU  - Marrero, J. F.
AU  - Valdés, O.
AU  - Rivera, D. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 25
UR  - 
DO  - 10.1002/chem.201805318
AB  - The multicomponent backbone N‐modification of peptides on solid‐phase is presented as a powerful and general method to enable peptide stapling at the backbone instead of the side chains. This work shows that a variety of functionalized N‐substituents suitable for backbone stapling can be readily introduced by means of on‐resin Ugi multicomponent reactions conducted during solid‐phase peptide synthesis. Diverse macrocyclization chemistries were implemented with such backbone N‐substituents, including the ring‐closing metathesis, lactamization, and thiol alkylation. The backbone N‐modification method was also applied to the synthesis of α‐helical peptides by linking N‐substituents to the peptide N‐terminus, thus featuring hydrogen‐bond surrogate structures. Overall, the strategy proves useful for peptide backbone macrocyclization approaches that show promise in peptide drug discovery.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 715
TI  - Natural urease inhibitors from Aloe vera resin and Lycium shawii and their structural-activity relationship and molecular docking study
JO  - Bioorg. Chem.
PY  - 2019
SP  - 102955
AU  - Rehman, N. U.
AU  - Khan, A.
AU  - Al-Harrasi, A.
AU  - Khiat, M.
AU  - Hussain, H.
AU  - Wadood, A.
AU  - Riaz, M.
AU  - 
VL  - 88
UR  - 
DO  - 10.1016/j.bioorg.2019.102955
AB  - Bio-assay guided fractionation of the methanolic extract of Aloe vera resin and Lycium shawii stem successively afforded twenty three compounds; fourteen (1–14) from A. vera and nine (15–23) from L. shawii. All these compounds were characterized by 1D and 2D NMR spectroscopic techniques viz., 1H, 13C, DEPT, HSQC, HMBC, and COSY, and NEOSY, ESI-MS and compared with the reported literature. These compounds were assessed for their potential as urease inhibitors targeted in peptic ulcer. Among crude extracts and fractions of A. vera resin, n-butanol fraction (23.5 ± 1.7 μg·mL−1) showed the most potent urease inhibition followed by methanol (30.9 ± 0.3 μg/mL) and ethyl acetate (31.7 ± 0.5 μg·mL−1). In case of L. shawii, ethyl acetate fraction exhibited the highest urease activity (41.0 ± 1.4 μg/mL) trailed by dichloromethane (55.2 ± 1.5 μg/mL) fraction. Among the isolates, compounds 7, 11 and 23 were found to be excellent urease inhibitors with IC50 values of 14.5 ± 0.90 µM, (16.7 ± 0.16 µM) and 14.0 ± 0.8 µM, respectively. To the best of our knowledge, this is the first report on the urease enzyme inhibitory activity of the said compounds excluding compound 18. In addition, the urease activity of different fractions of L. shawii stem was also reported for the first time. The molecular docking studies showed that all the active compounds well accommodate in the active site of the urease enzyme by interacting with key amino acids.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 714
TI  - Chemical Constituents of Acridocarpus orientalis and Their Chemotaxonomic Significance
JO  - Chem. Nat. Compd.
PY  - 2019
SP  - 586-588
AU  - Rehman, N. U.
AU  - Hussain, H.
AU  - Ali, L.
AU  - Khan, A.
AU  - Mabood, F.
AU  - Shinwari, Z. K.
AU  - Hussain, J.
AU  - Al-Harrasi, A.
AU  - 
VL  - 55
UR  - 
DO  - 10.1007/s10600-019-02752-1
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 711
TI  - Thin Film Chemical Deposition Techniques as a Tool for Fingerprinting of Free Fatty Acids by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry
JO  - Anal. Chem.
PY  - 2019
SP  - 1636-1643
AU  - Podolskaya, E. P.
AU  - Gladchuk, A. S.
AU  - Keltsieva, O. A.
AU  - Dubakova, P. S.
AU  - Silyavka, E. S.
AU  - Lukasheva, E.
AU  - Zhukov, V.
AU  - Lapina, N.
AU  - Makhmadalieva, M. R.
AU  - Gzgzyan, A. M.
AU  - Sukhodolov, N. G.
AU  - Krasnov, K. A.
AU  - Selyutin, A. A.
AU  - Frolov, A.
AU  - 
VL  - 91
UR  - 
DO  - 10.1021/acs.analchem.8b05296
AB  - Metabolic fingerprinting is a powerful analytical technique, giving access to high-throughput identification and relative quantification of multiple metabolites. Because of short analysis times, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) is the preferred instrumental platform for fingerprinting, although its power in analysis of free fatty acids (FFAs) is limited. However, these metabolites are the biomarkers of human pathologies and indicators of food quality. Hence, a high-throughput method for their fingerprinting is required. Therefore, here we propose a MALDI-TOF-MS method for identification and relative quantification of FFAs in biological samples of different origins. Our approach relies on formation of monomolecular Langmuir films (LFs) at the interphase of aqueous barium acetate solution, supplemented with low amounts of 2,5-dihydroxybenzoic acid, and hexane extracts of biological samples. This resulted in detection limits of 10–13–10–14 mol and overall method linear dynamic range of at least 4 orders of magnitude with accuracy and precision within 2 and 17%, respectively. The method precision was verified with eight sample series of different taxonomies, which indicates a universal applicability of our approach. Thereby, 31 and 22 FFA signals were annotated by exact mass and identified by tandem MS, respectively. Among 20 FFAs identified in Fucus algae, 14 could be confirmed by gas chromatography-mass spectrometry.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 706
TI  - In vitro anticancer evaluation of novel triphenyltin(IV) compounds with some N-acetyl-S-(naphthoquinone)cysteine derivatives
JO  - J. Serb. Chem. Soc.
PY  - 2019
SP  - 1119-1127
AU  - Pantelić, N. ?.
AU  - Lerbs, M.
AU  - Wolf, K.
AU  - Wessjohann, L. A.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 84
UR  - 
DO  - 10.2298/JSC190322032P
AB  - Triphenyltin(IV) compounds with naphthoquinone derivatives containing N-acetylcysteine, N-acetyl-S-(1,2-dion-4-naphthyl)cysteine (1,2-NQC), 1, and N-acetyl-S-(1,4-dion-2-naphthyl)cysteine (1,4-NQC), 2, were synthesized and characterized by elemental microanalysis, IR, multinuclear (1H, 13C, 119Sn) NMR spectroscopy as well as HR-ESI mass spectrometry. With the aim of in vitro anticancer activity determination of ligand precursors and novel synthesized organotin(IV) compounds against human cervix adenocarcinoma (HeLa), human colon carcinoma (HT-29), and melanoma carcinoma cell line (B16F10), MTT colorimetric assay method was applied. The results indicate that synthesized compounds exhibited remarkable antiproliferative activity toward all tested cell lines with IC50 in the range of 0.17 to 0.87 μM. Complex 1 showed the greatest activity against HT-29 cells, with IC50 value of 0.21 ± 0.01 μM, 119 times better than cisplatin, while complex 2 demonstrated the highest activity toward HeLa cells, IC50 = 0.17 ± 0.01 μM, which is ~26 times better than cisplatin.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 705
TI  - French maritime pine bark treatment decelerates plaque development and improves spatial memory in Alzheimer&#39;s disease mice
JO  - Phytomedicine
PY  - 2019
SP  - 39-48
AU  - Paarmann, K.
AU  - Prakash, S. R.
AU  - Krohn, M.
AU  - Möhle, L.
AU  - Brackhan, M.
AU  - Brüning, T.
AU  - Eiriz, I.
AU  - Pahnke, J.
AU  - 
VL  - 57
UR  - 
DO  - 10.1016/j.phymed.2018.11.033
AB  - BackgroundPlant extracts are increasingly investigated as potential drugs against Alzheimer&#39;s disease (AD) and dementia in general. Pycnogenol is an extract from the bark of the French maritime pine (Pinus pinaster Aiton subsp. atlantica) with known anti-oxidative and neuroprotective effects.Hypothesis/PurposePycnogenol is thought to improve cognitive functions in elderly. We wanted to investigate and quantify these effects in a model system of cerebral ß-amyloidosis/AD.Study design/methodsThis study experimentally assessed the effects of Pycnogenol on AD-related pathology in a ß-amyloidosis mouse model. APP-transgenic mice and controls were treated orally in a pre-onset and post-onset treatment paradigm. The effects of Pycnogenol were characterized by analysing ß-amyloid (Aß) plaques, number of neurons, glia coverage, myelination pattern, and cortical coverage with axons using immunohistochemistry. Aß levels were quantified using ELISA and gene expression levels of APP-processing enzymes ADAM10, BACE1 and IDE protein levels were determined by Western blot. Behavioural changes in circadian rhythm were monitored and spatial memory / cognition was assessed using a water maze test.ResultsPycnogenol significantly decreased the number of plaques in both treatment paradigms but did not alter levels of soluble Aß or the gene expression of APP-processing enzymes. The morphological analyses revealed no changes in the number of neurons, astrocytes, microglia, the myelination pattern, or the morphology of axons. Behavioural testing revealed an improvement of the spatial memory in the pre-onset treatment paradigm only.ConclusionOur results suggest to evaluate clinically a potential use of Pycnogenol in the prevention or in early stages of mild cognitive impairment (MCI) and AD.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 727
TI  - The unusual fragmentation of long-chain feruloyl esters under negative ion electrospray conditions
JO  - J. Mass Spectrom.
PY  - 2019
SP  - 549-556
AU  - Schmidt, J.
AU  - Kuck, D.
AU  - Franke, K.
AU  - Sultani, H.
AU  - Laub, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 54
UR  - 
DO  - 10.1002/jms.4357
AB  - Long‐chain ferulic acid esters, such as eicosyl ferulate (1), show a complex and analytically valuable fragmentation behavior under negative‐ion electrospay collision‐induced dissociation ((‐)‐ESI‐CID) mass spectrometry, as studied by use of a high‐resolution (Orbitrap) mass spectrometer. In a strong contrast to the very simple fragmentation of the [M + H]+ ion, which is discussed briefly, the deprotonated molecule, [M ‐ H]‐, exhibits a rich secondary fragmentation chemistry. It first loses a methyl radical (MS2) and the ortho‐quinoid [M ‐ H ‐ Me]‐• radical anion thus formed then dissociates by loss of an extended series of neutral radicals, CnH2n+1• (n = 0‐16) from the long alkyl chain, in competition with the expulsion of CO and CO2 (MS3). The further fragmentation (MS4) of the [M ‐ H ‐ Me ‐ C3H7]‐ ion, discussed as an example, and the highly specific losses of alkyl radicals from the [M ‐ H ‐ Me ‐ CO]‐• and [M ‐ H ‐ Me ‐ CO2]‐• ions provide some mechanistic and structural insights.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 703
TI  - Furoquinolines and dihydrooxazole alkaloids with cytotoxic activity from the stem bark of Araliopsis soyauxii
JO  - Fitoterapia
PY  - 2019
SP  - 193-199
AU  - Nganou, B. K.
AU  - Mbaveng, A. T.
AU  - Fobofou, S. A. T.
AU  - Fankam, A. G.
AU  - Bitchagno, G. T. M.
AU  - Simo Mpetga, J. D.
AU  - Wessjohann, L. A.
AU  - Kuete, V.
AU  - Efferth, T.
AU  - Tane, P.
AU  - 
VL  - 133
UR  - 
DO  - 10.1016/j.fitote.2019.01.003
AB  - Two new furoquinoline alkaloids, maculine B (1) and kokusaginine B (2) and one new dihydrooxazole alkaloid, veprisazole (3), along with four known compounds namely, N13-methyl-3-methoxyrutaecarpine (4), flindersiamine (5), skimmianine (6) and tilianin (7) were isolated from the methanol extract of the stem bark of Araliopsis soyauxii Engl. by various chromatographic methods. Their structures were determined using spectrometry and spectroscopic techniques including NMR and MS. The cytotoxicity of the new compounds compared to that of doxorubicin, the reference anticancer compound, was determined on a panel of nine cancer cell lines including sensitive and drug resistant phenotypes. The three previously undescribed alkaloids displayed selective activities. Maculine B (1), the most active one among the newly described compounds, exhibited IC50 below 30 μM against CCRF-CEM leukemia and U87MG glioblastoma cells.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 696
TI  - Discovery of potent and selective inhibitors of the Escherichia coli M1-aminopeptidase via multicomponent solid-phase synthesis of tetrazole-peptidomimetics
JO  - Eur. J. Med. Chem.
PY  - 2019
SP  - 481-499
AU  - Méndez, Y.
AU  - De Armas, G.
AU  - Pérez, I.
AU  - Rojas, T.
AU  - Valdés-Tresanco, M. E.
AU  - Izquierdo, M.
AU  - Alonso del Rivero, M.
AU  - Álvarez-Ginarte, Y. M.
AU  - Valiente, P. A.
AU  - Soto, C.
AU  - de León, L.
AU  - Vasco, A. V.
AU  - Scott, W. L.
AU  - Westermann, B.
AU  - González-Bacerio, J.
AU  - Rivera, D. G.
AU  - 
VL  - 163
UR  - 
DO  - 10.1016/j.ejmech.2018.11.074
AB  - The Escherichia coli neutral M1-aminopeptidase (ePepN) is a novel target identified for the development of antimicrobials. Here we describe a solid-phase multicomponent approach which enabled the discovery of potent ePepN inhibitors. The on-resin protocol, developed in the frame of the Distributed Drug Discovery (D3) program, comprises the implementation of parallel Ugi-azide four-component reactions with resin-bound amino acids, thus leading to the rapid preparation of a focused library of tetrazole-peptidomimetics (TPMs) suitable for biological screening. By dose-response studies, three compounds were identified as potent and selective ePepN inhibitors, as little inhibitory effect was exhibited for the porcine ortholog aminopeptidase. The study allowed for the identification of the key structural features required for a high ePepN inhibitory activity. The most potent and selective inhibitor (TPM 11) showed a non-competitive inhibition profile of ePepN. We predicted that both diastereomers of compound TPM 11 bind to a site distinct from that occupied by the substrate. Theoretical models suggested that TPM 11 has an alternative inhibition mechanism that doesn&#39;t involve Zn coordination. On the other hand, the activity landscape analysis provided a rationale for our findings. Of note, compound TMP 2 showed in vitro antibacterial activity against Escherichia coli. Furthermore, none of the three identified inhibitors is a potent haemolytic agent, and only two compounds showed moderate cytotoxic activity toward the murine myeloma P3X63Ag cells. These results point to promising compounds for the future development of rationally designed TPMs as antibacterial agents.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 695
TI  - Anti-Inflammatory Activity of A Polyphenolic Extract from Arabidopsis thaliana in In Vitro and In Vivo Models of Alzheimer’s Disease
JO  - Int. J. Mol. Sci.
PY  - 2019
SP  - 708
AU  - Mattioli, R.
AU  - Francioso, A.
AU  - d’Erme, M.
AU  - Trovato, M.
AU  - Mancini, P.
AU  - Piacentini, L.
AU  - Casale, A. M.
AU  - Wessjohann, L.
AU  - Gazzino, R.
AU  - Costantino, P.
AU  - Mosca, L.
AU  - 
VL  - 20
UR  - 
DO  - 10.3390/ijms20030708
AB  - Alzheimer’s disease (AD) is the most common neurodegenerative disorder and the primary form of dementia in the elderly. One of the main features of AD is the increase in amyloid-beta (Aβ) peptide production and aggregation, leading to oxidative stress, neuroinflammation and neurodegeneration. Polyphenols are well known for their antioxidant, anti-inflammatory and neuroprotective effects and have been proposed as possible therapeutic agents against AD. Here, we investigated the effects of a polyphenolic extract of Arabidopsis thaliana (a plant belonging to the Brassicaceae family) on inflammatory response induced by Aβ. BV2 murine microglia cells treated with both Aβ25–35 peptide and extract showed a lower pro-inflammatory (IL-6, IL-1β, TNF-α) and a higher anti-inflammatory (IL-4, IL-10, IL-13) cytokine production compared to cells treated with Aβ only. The activation of the Nrf2-antioxidant response element signaling pathway in treated cells resulted in the upregulation of heme oxygenase-1 mRNA and in an increase of NAD(P)H:quinone oxidoreductase 1 activity. To establish whether the extract is also effective against Aβ-induced neurotoxicity in vivo, we evaluated its effect on the impaired climbing ability of AD Drosophila flies expressing human Aβ1–42. Arabidopsis extract significantly restored the locomotor activity of these flies, thus confirming its neuroprotective effects also in vivo. These results point to a protective effect of the Arabidopsis extract in AD, and prompt its use as a model in studying the impact of complex mixtures derived from plant-based food on neurodegenerative diseases.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 694
TI  - A substrate of the ABC transporter PEN3 stimulates bacterial flagellin (flg22)-induced callose deposition in Arabidopsis thaliana
JO  - J. Biol. Chem.
PY  - 2019
SP  - 6857-6870
AU  - Matern, A.
AU  - Böttcher, C.
AU  - Eschen-Lippold, L.
AU  - Westermann, B.
AU  - Smolka, U.
AU  - Döll, S.
AU  - Trempel, F.
AU  - Aryal, B.
AU  - Scheel, D.
AU  - Geisler, M.
AU  - Rosahl, S.
AU  - 
VL  - 294
UR  - 
DO  - 10.1074/jbc.RA119.007676
AB  - Nonhost resistance of Arabidopsis thaliana against Phytophthora infestans, a filamentous eukaryotic microbe and the causal agent of potato late blight, is based on a multilayered defense system. Arabidopsis thaliana controls pathogen entry through the penetration-resistance genes PEN2 and PEN3, encoding an atypical myrosinase and an ABC transporter, respectively, required for synthesis and export of unknown indole compounds. To identify pathogen-elicited leaf surface metabolites and further unravel nonhost resistance in Arabidopsis, we performed untargeted metabolite profiling by incubating a P. infestans zoospore suspension on leaves of WT or pen3 mutant Arabidopsis plants. Among the plant-secreted metabolites, 4-methoxyindol-3-yl-methanol and S-(4-methoxy-indol-3-yl-methyl) cysteine were detected in spore suspensions recollected from WT plants, but at reduced levels from the pen3 mutant plants. In both whole-cell and microsome-based assays, 4-methoxyindol-3-yl-methanol was transported in a PEN3-dependent manner, suggesting that this compound is a PEN3 substrate. The syntheses of both compounds were dependent on functional PEN2 and phytochelatin synthase 1. None of these compounds inhibited mycelial growth of P. infestans in vitro. Of note, exogenous application of 4-methoxyindol-3-yl methanol slightly elevated cytosolic Ca2+ levels and enhanced callose deposition in hydathodes of seedlings treated with a bacterial pathogen-associated molecular pattern (PAMP), flagellin (flg22). Loss of flg22-induced callose deposition in leaves of pen3 seedlings was partially reverted by the addition of 4-methoxyindol-3-yl methanol. In conclusion, we have identified a specific indole compound that is a substrate for PEN3 and contributes to the plant defense response against microbial pathogens.
A2  - 
C1  - Biochemistry of Plant Interactions; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 693
TI  - Profiling of Seed Proteome in Pea (Pisum sativum L.) Lines Characterized with High and Low Responsivity to Combined Inoculation with Nodule Bacteria and Arbuscular Mycorrhizal Fungi
JO  - Molecules
PY  - 2019
SP  - 1603
AU  - Mamontova, T.
AU  - Afonin, A. M.
AU  - Ihling, C.
AU  - Soboleva, A.
AU  - Lukasheva, E.
AU  - Sulima, A. S.
AU  - Shtark, O. Y.
AU  - Akhtemova, G. A.
AU  - Povydysh, M. N.
AU  - Sinz, A.
AU  - Frolov, A.
AU  - Zhukov, V. A.
AU  - Tikhonovich, I. A.
AU  - 
VL  - 24
UR  - 
DO  - 10.3390/molecules24081603
AB  - Legume crops represent the major source of food protein and contribute to human nutrition and animal feeding. An essential improvement of their productivity can be achieved by symbiosis with beneficial soil microorganisms—rhizobia (Rh) and arbuscular mycorrhizal (AM) fungi. The efficiency of these interactions depends on plant genotype. Recently, we have shown that, after simultaneous inoculation with Rh and AM, the productivity gain of pea (Pisum sativum L) line K-8274, characterized by high efficiency of interaction with soil microorganisms (EIBSM), was higher in comparison to a low-EIBSM line K-3358. However, the molecular mechanisms behind this effect are still uncharacterized. Therefore, here, we address the alterations in pea seed proteome, underlying the symbiosis-related productivity gain, and identify 111 differentially expressed proteins in the two lines. The high-EIBSM line K-8274 responded to inoculation by prolongation of seed maturation, manifested by up-regulation of proteins involved in cellular respiration, protein biosynthesis, and down-regulation of late-embryogenesis abundant (LEA) proteins. In contrast, the low-EIBSM line K-3358 demonstrated lower levels of the proteins, related to cell metabolism. Thus, we propose that the EIBSM trait is linked to prolongation of seed filling that needs to be taken into account in pulse crop breeding programs. The raw data have been deposited to the ProteomeXchange with identifier PXD013479.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 692
TI  - Triterpene-Based Carboxamides Act as Good Inhibitors of Butyrylcholinesterase
JO  - Molecules
PY  - 2019
SP  - 948
AU  - Loesche, A.
AU  - Kahnt, M.
AU  - Serbian, I.
AU  - Brandt, W.
AU  - Csuk, R.
AU  - 
VL  - 24
UR  - 
DO  - 10.3390/molecules24050948
AB  - A set of overall 40 carboxamides was prepared from five different natural occurring triterpenoids including oleanolic, ursolic, maslinic, betulinic, and platanic acid. All of which were derived from ethylene diamine holding an additional substituent connected to the ethylene diamine group. These derivatives were evaluated regarding their inhibitory activity of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) employing Ellman’s assay. We further determined the type of inhibition and inhibition constants. Carboxamides derived from platanic acid have been shown to be potent and selective BChE inhibitors. Especially the mixed-type inhibitor (3β)-N-(2-pyrrolidin-1-ylethyl)-3-acetyloxy-20-oxo-30-norlupan-28-amide (35) showed a remarkably low Ki of 0.07 ± 0.01 µM (Ki′ = 2.38 ± 0.48 µM) for the inhibition of BChE.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 691
TI  - Novel 12-hydroxydehydroabietylamine derivatives act as potent and selective butyrylcholinesterase inhibitors
JO  - Bioorg. Chem.
PY  - 2019
SP  - 103092
AU  - Loesche, A.
AU  - Wiemann, J.
AU  - Rohmer, M.
AU  - Brandt, W.
AU  - Csuk, R.
AU  - 
VL  - 90
UR  - 
DO  - 10.1016/j.bioorg.2019.103092
AB  - The skeleton of the diterpene dehydroabietylamine was modified, and a set of 12-hydroxy-dehydroabietylamine derivatives was obtained. The compounds were screened in colorimetric Ellman’s assays to determine their ability to act as inhibitors for the enzymes acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum). Additional investigations concerning the enzyme kinetics were performed and showed 12-hydroxy-N-(4-nitro-benzoyl)dehydroabietylamine (13) and 12-hydroxy-N-(isonicotinoyl)dehydroabietylamine (17) as selective BChE inhibitors holding good inhibition constants Ki = 0.72 ± 0.06 μM and Ki = 0.86 ± 0.19 μM, respectively.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 690
TI  - Nor-guanacastepene pigments from the Chilean mushroom Cortinarius pyromyxa
JO  - Phytochemistry
PY  - 2019
SP  - 112048
AU  - Lam, Y. T. H.
AU  - Palfner, G.
AU  - Lima, C.
AU  - Porzel, A.
AU  - Brandt, W.
AU  - Frolov, A.
AU  - Sultani, H.
AU  - Franke, K.
AU  - Wagner, C.
AU  - Merzweiler, K.
AU  - Wessjohann, L. A.
AU  - Arnold, N.
AU  - 
VL  - 165
UR  - 
DO  - 10.1016/j.phytochem.2019.05.021
AB  - For the first time, the pigment composition of basidiocarps from the Chilean mushroom Cortinarius pyromyxa was studied under various aspects like phylogeny, chemistry and antibiotic activity. A molecular biological study supports the monotypic position of C. pyromyxa in subgenus Myxacium, genus Cortinarius. Four undescribed diterpenoids, named pyromyxones A-D, were isolated from fruiting bodies of C. pyromyxa. Their chemical structures were elucidated based on comprehensive one- and two-dimensional NMR spectroscopic analysis, ESI-HRMS measurements, as well as X-ray crystallography. In addition, the absolute configurations of pyromyxones A-D were established with the aid of JH,H, NOESY spectra and quantum chemical CD calculation. The pyromyxones A-D possess the undescribed nor-guanacastane skeleton. Tested pyromyxones A, B, and D exhibit only weak activity against gram-positive Bacillus subtilis and gram-negative Aliivibrio fischeri as well as the phytopathogenic fungi Botrytis cinerea, Septoria tritici and Phytophthora infestans.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 689
TI  - Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells
JO  - Beilstein J. Org. Chem.
PY  - 2019
SP  - 96-105
AU  - Kufka, R.
AU  - Rennert, R.
AU  - Kaluđerović, G. N.
AU  - Weber, L.
AU  - Richter, W.
AU  - Wessjohann, L. A.
AU  - 
VL  - 15
UR  - 
DO  - 10.3762/bjoc.15.11
AB  - Tubugi-1 is a small cytotoxic peptide with picomolar cytotoxicity. To improve its cancer cell targeting, it was conjugated using a universal, modular disulfide derivative. This allowed conjugation to a neuropeptide-Y (NPY)-inspired peptide [K4(C-βA-),F7,L17,P34]-hNPY, acting as NPY Y1 receptor (hY1R)-targeting peptide, to form a tubugi-1–SS–NPY disulfide-linked conjugate. The cytotoxic impacts of the novel tubugi-1–NPY peptide–toxin conjugate, as well as of free tubugi-1, and tubugi-1 bearing the thiol spacer (liberated from tubugi-1–NPY conjugate), and native tubulysin A as reference were investigated by in vitro cell viability and proliferation screenings. The tumor cell lines HT-29, Colo320 (both colon cancer), PC-3 (prostate cancer), and in conjunction with RT-qPCR analyses of the hY1R expression, the cell lines SK-N-MC (Ewing`s sarcoma), MDA-MB-468, MDA-MB-231 (both breast cancer) and 184B5 (normal breast; chemically transformed) were investigated. As hoped, the toxicity of tubugi-1 was masked, with IC50 values decreased by ca. 1,000-fold compared to the free toxin. Due to intracellular linker cleavage, the cytotoxic potency of the liberated tubugi-1 that, however, still bears the thiol spacer (tubugi-1-SH) was restored and up to 10-fold higher compared to the entire peptide–toxin conjugate. The conjugate shows toxic selectivity to tumor cell lines overexpressing the hY1R receptor subtype like, e.g., the hard to treat triple-negative breast cancer MDA-MB-468 cells.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 688
TI  - Generation and Characterization of an Abcc1 Humanized Mouse Model (hABCC1flx/flx) with Knockout Capability
JO  - Mol. Pharmacol.
PY  - 2019
SP  - 138-147
AU  - Krohn, M.
AU  - Zoufal, V.
AU  - Mairinger, S.
AU  - Wanek, T.
AU  - Paarmann, K.
AU  - Brüning, T.
AU  - Eiriz, I.
AU  - Brackhan, M.
AU  - Langer, O.
AU  - Pahnke, J.
AU  - 
VL  - 96
UR  - 
DO  - 10.1124/mol.119.115824
AB  - ATP-binding cassette (ABC) transporters such as ABCB1 (P-glycoprotein), ABCC1 (MRP1), and ABCG2 (BCRP) are well known for their role in rendering cancer cells resistant to chemotherapy. Additionally, recent research provided evidence that, along with other ABC transporters (ABCA1 and ABCA7), they might be cornerstones to tackle neurodegenerative diseases. Overcoming chemoresistance in cancer, understanding drug-drug interactions, and developing efficient and specific drugs that alter ABC transporter function are hindered by a lack of in vivo research models, which are fully predictive for humans. Hence, the humanization of ABC transporters in mice has become a major focus in pharmaceutical and neurodegenerative research. Here, we present a characterization of the first Abcc1 humanized mouse line. To preserve endogenous expression profiles, we chose to generate a knockin mouse model that leads to the expression of a chimeric protein that is fully human except for one amino acid. We found robust mRNA and protein expression within all major organs analyzed (brain, lung, spleen, and kidney). Furthermore, we demonstrate the functionality of the expressed human ABCC1 protein in brain and lungs using functional positron emission tomography imaging in vivo. Through the introduction of loxP sites, we additionally enabled this humanized mouse model for highly sophisticated studies involving cell type–specific transporter ablation. Based on our data, the presented mouse model appears to be a promising tool for the investigation of cell-specific ABCC1 function. It can provide a new basis for better translation of preclinical research.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 687
TI  - The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model
JO  - Food Chem. Toxicol.
PY  - 2019
SP  - 257-268
AU  - Krajnović, T.
AU  - Drača, D.
AU  - Kaluđerović, G. N.
AU  - Dunđerović, D.
AU  - Mirkov, I.
AU  - Wessjohann, L. A.
AU  - Maksimović-Ivanić, D.
AU  - Mijatović, S.
AU  - 
VL  - 129
UR  - 
DO  - 10.1016/j.fct.2019.04.046
AB  - Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, gained increasing attention as a potential chemopreventive agent. In the present study, IXN antimetastatic potential in vitro against the highly invasive melanoma cell line B16-F10 and in vivo in a murine metastatic model was investigated. Melanoma cell viability was diminished in a dose-dependent manner following the treatment with IXN. This decrease was a consequence of autophagy and caspase-dependent apoptosis. Additionally, the dividing potential of highly proliferative melanoma cells was dramatically affected by this isoflavanone, which was in correlation with an abrogated cell colony forming potential, indicating changes in their metastatic features. Concordantly, IXN promoted strong suppression of the processes that define metastasis– cell adhesion, invasion, and migration. Further investigation at the molecular level revealed that the abolished metastatic potential of a melanoma subclone was due to disrupted integrin signaling. Importantly, these results were reaffirmed in vivo where IXN inhibited the development of lung metastatic foci in tumor-challenged animals. The results of the present study may highlight the beneficial effects of IXN on melanoma as the most aggressive type of skin cancer and will hopefully shed a light on the possible use of this prenylflavonoid in the treatment of metastatic malignancies.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 685
TI  - Therapeutic Potential of Iridoid Derivatives: Patent Review
JO  - Inventions
PY  - 2019
SP  - 29
AU  - Hussain, H.
AU  - Green, I. R.
AU  - Saleem, M.
AU  - Raza, M. L.
AU  - Nazir, M.
AU  - 
VL  - 4
UR  - 
DO  - 10.3390/inventions4020029
AB  - Iridoids belong to a family of monoterpenoids comprising the cyclopentan[c]-pyran system; this class of compounds offers a wide range of biological effects, namely antileishmanial, anticancer, antiplasmodial, and anti-inflammatory potency. To date, a large number of biologically active iridoid derivatives have been reported from various plant families, including Rubiaceae, Plantaginaceae, Scrophulariaceae, and Verbenaceae. Furthermore, iridoids have the potential to form conjugates with other anticancer, antidiabetic, antileishmanial, and antimalarial drugs which synergistically have the potential to increase their effects. Additionally, future research should focus on the synthesis of halo analogs as well as preparing homo dimers or heterodimers of iridoids, since these might quite conceivably possess an increased bioactivity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 682
TI  - Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential anti-diabetes agents: patent review (2015-2018)
JO  - Expert Opin. Ther. Pat.
PY  - 2019
SP  - 689-702
AU  - Hussain, H.
AU  - Green, I. R.
AU  - Abbas, G.
AU  - Adekenov, S. M.
AU  - Hussain, W.
AU  - Ali, I.
AU  - 
VL  - 29
UR  - 
DO  - 10.1080/13543776.2019.1655542
AB  - Introduction: Protein tyrosine phosphatase 1B (PTP1B) inhibition has been recommended as a crucial strategy to enhance insulin sensitivity in various cells and this fact is supported by human genetic data. PTP1B inhibitors improve the sensitivity of the insulin receptor and have the ability to cure insulin resistance-related diseases. In the latter years, targeting PTP1B inhibitors is being considered an attractive target to treat T2DM and therefore libraries of PTP1B inhibitors are being suggested as potent antidiabetic drugs.Areas covered: This review provides an overview of published patents from January 2015 to December 2018. The review describes the effectiveness of potent PTP1B inhibitors as pharmaceutical agents to treat type 2 diabetes.Expert opinion: Enormous developments have been made in PTP1B drug discovery which describes progress in natural products, synthetic heterocyclic scaffolds or heterocyclic hybrid compounds. Various protocols are being followed to boost the pharmacological effects of PTP1B inhibitors. Moreover these new advancements suggest that it is possible to get small-molecule PTP1B inhibitors with the required potency and selectivity. Furthermore, future endevours via an integrated strategy of using medicinal chemistry and structural biology will hopefully result in potent and selective PTP1B inhibitors as well as safer and more effective orally available drugs.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 681
TI  - Dipeptidyl peptidase IV inhibitors as a potential target for diabetes: patent review (2015-2018)
JO  - Expert Opin. Ther. Pat.
PY  - 2019
SP  - 535-553
AU  - Hussain, H.
AU  - Abbas, G.
AU  - Green, I. R.
AU  - Ali, I.
AU  - 
VL  - 29
UR  - 
DO  - 10.1080/13543776.2019.1632290
AB  - Introduction: Dipeptidyl peptidase 4 (DPP-4) belongs to the family of serine proteases and is involved in the degradation of GLP-1 and GIP hormones, which enhance the production and release of insulin. Targeting DPP-4 inhibitors is increasingly being considered as promising paradigms to treat type 2 diabetes mellitus and therefore DPP-4 inhibitors are being considered as promising antidiabetic drugs.Areas covered: This review provides an overview of published patents describing natural and synthetic DPP-4 inhibitors from January 2015 to December 2018.Expert opinion: A fair number of new synthetic and natural DPP-4 inhibitors have been reported in last four years which describe the progress in the development of various heterocyclic scaffolds or heterocyclic hybrid compounds. As a result of this, many marketed DPP-4 inhibitors that have been approved by the appropriate governing bodies during the past decade, have been introduced as inhibitors. Molecular hybridization is an emerging idea in medicinal chemistry and therefore hybrid compounds of DPP-4 inhibitors with other DPP-4 inhibitors or with antidiabetic drugs should be formulated for a comprehensive evaluation. More detailed pharmacovigilance of DPP-4 inhibitors is required because this will address the pancreas-related adverse events as well as their impact on cardiovascular outcomes via long-term studies.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 680
TI  - Cucurbitacins as Anticancer Agents: A Patent Review
JO  - Recent Pat. Anti-Canc. Drug Discov.
PY  - 2019
SP  - 133-143
AU  - Hussain, H.
AU  - Green, I. R.
AU  - Saleem, M.
AU  - Khattak, K. F.
AU  - Irshad, M.
AU  - Ali, M.
AU  - 
VL  - 14
UR  - 
DO  - 10.2174/1574892813666181119123035
AB  - Background: Cucurbitacins belong to a group of tetracyclic triterpenoids that display a wide range of biological effects. In the past, numerous cucurbitacins have been isolated from natural sources and many active compounds have been synthesized using the privileged scaffold in order to enhance its cytotoxic effects.Objective: This review covers patents on the therapeutic effects of natural cucurbitacins and their synthetic analogs published during the past decade. By far, the majority of patents published are related to cancer and Structure-Activity Relationships (SAR) of these compounds are included to lend gravitas to this important class of natural products.Methods: The date about the published patents was downloaded via online open access patent databases.Results: Cucurbitacins display significant cytotoxic properties, in particular cucurbitacins B and D which possess very potent effects towards a number of cancer cells. Numerous cucurbitacins isolated from natural sources have been derivatized through chemical modification at the C(2)-OH and C(25)OH groups. Most importantly, an acyl ester of the C(25)-OH and, iso-propyl, n-propyl and ethyl ether groups of the C(2)-OH demonstrated the most increased cytotoxic activity.Conclusion: The significant cytotoxic effects of natural and semi-synthetic cucurbitacins make them attractive as new drug candidates. Moreover, cucurbitacins have the capability to form conjugates with other anticancer drugs which will synergistically enhance their anticancer effects. The authors believe that in order to get lead compounds, there should be a greater focus on the synthesis of homodimers, heterodimers, and halo derivatives of cucurbitacins. In the opinion of the authors the analysis of the published patents on the cucurbitacins indicates that these compounds can be developed into a regimen to treat a wide spectrum of cancers.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 678
TI  - Modification of Lignoboost Kraft Lignin from softwoods with dihydroxybenzenes
JO  - React. Funct. Polym.
PY  - 2019
SP  - 112-118
AU  - Hoffmann, A.
AU  - Nong, J. P.
AU  - Porzel, A.
AU  - Bremer, M.
AU  - Fischer, S.
AU  - 
VL  - 142
UR  - 
DO  - 10.1016/j.reactfunctpolym.2019.06.011
AB  - Lignin, a component of the cell walls of plants and the second most abundant biopolymer has long been regarded as disturbing substance in pulp production by paper industry. This view has changed in recent decades. Thus, lignin is increasingly regarded as an alternative to crude oil. Tuned and modified lignins have suitable properties to use them as building blocks for various applications as well as for the production of basic chemicals. By modifying lignin, its reactivity and uniformity can be increased. In addition, properties of the lignin can be changed and influenced by selective modification. By a solvent-free modification with dihydroxybenzene, aliphatic OH groups of the lignin side chain can be removed and covalent CC bonds to the aromatics can be formed. At the same time, aryl-alkyl ether cleavage occurs, which reduces the molecular weight of lignin by about one third. In addition, ongoing reactions result in the reduction in the molecular weight distribution. All this leads to a more uniform and reactive lignin which is interesting as a precursor for various applications. This work provides a deeper understanding of ongoing reactions with dihydroxybenzenes and the structure of modified lignins.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 666
TI  - A cytochrome P450 from the mustard leaf beetles hydroxylates geraniol, a key step in iridoid biosynthesis
JO  - Insect Biochem. Mol. Biol.
PY  - 2019
SP  - 103212
AU  - Fu, N.
AU  - Yang, Z.-l.
AU  - Pauchet, Y.
AU  - Paetz, C.
AU  - Brandt, W.
AU  - Boland, W.
AU  - Burse, A.
AU  - 
VL  - 113
UR  - 
DO  - 10.1016/j.ibmb.2019.103212
AB  - Larvae of the leaf beetle Phaedon cochleariae synthesize the iridoid chysomelidial via the mevalonate pathway to repel predators. The normal terpenoid biosynthesis is integrated into the dedicated defensive pathway by the ω-hydroxylation of geraniol to (2E,6E)-2,6-dimethylocta-2,6-diene-1,8-diol (ω-OH-geraniol). Here we identify and characterize the P450 monooxygenase CYP6BH5 as the geraniol hydroxylase using integrated transcriptomics, proteomics and RNA interference (RNAi). In the fat body, 73 cytochrome P450s were identified, and CYP6BH5 was among those that were expressed specifically in fat body. Double stranded RNA mediated knockdown of CYP6BH5 led to a significant reduction of ω-hydroxygeraniol glucoside in the hemolymph and, later, of the chrysomelidial in the defensive secretion. Heterologously expressed CYP6BH5 converted geraniol to ω-OH-geraniol. In addition to geraniol, CYP6BH5 also catalyzes hydroxylation of other monoterpenols, such as nerol and citronellol to the corresponding α,ω-dihydroxy compounds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 665
TI  - Insights into the Phytochemistry of the Cuban Endemic Medicinal Plant Phyllanthus orbicularis: Fideloside, a Novel Bioactive 8-C-glycosyl 2,3-Dihydroflavonol
JO  - Molecules
PY  - 2019
SP  - 2855
AU  - Francioso, A.
AU  - Franke, K.
AU  - Villani, C.
AU  - Mosca, L.
AU  - d’Erme, M.
AU  - Frischbutter, S.
AU  - Brandt, W.
AU  - Sanchez-Lamar, A.
AU  - Wessjohann, L.
AU  - 
VL  - 24
UR  - 
DO  - 10.3390/molecules24152855
AB  - Phyllanthus orbicularis (Phyllanthaceae) is an endemic evergreen tropical plant of Cuba that grows in the western part of the island and is used in traditional medicine as an infusion. The aqueous extract of this plant presents a wide range of pharmacological activitiessuch as antimutagenic, antioxidant and antiviral effects. Given the many beneficial effects and the great interest in the development of new pharmacological products from natural sources, the aim of this work was to investigate the phytochemistry of this species and to elucidate the structure of the main bioactive principles. Besides the presence of several known polyphenols, the major constituent was hitherto not described. The chemical structure of this compound, here named Fideloside, was elucidated by means of HR-ESIMS/MSn, 1D/2D NMR, FT-IR, and ECD as (2R,3R)-(−)-3’,4′,5,7-tetrahydroxydihydroflavonol-8-C-β-D-glucopyranoside. The compound, as well as the plant aqueous preparations, showed promising bioactive properties, i.e., anti-inflammatory capacity in human explanted monocytes, corroborating future pharmacological use for this new natural C-glycosyl flavanonol.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 664
TI  - Antimicrobial secondary metabolites from the stem barks and leaves of Monotes kerstingii Gilg (Dipterocarpaceae)
JO  - Fitoterapia
PY  - 2019
SP  - 104239
AU  - Fotso, G. W.
AU  - Linda, M. K.
AU  - Dube, M.
AU  - Fobofou, S. A.
AU  - Albert, N. E.
AU  - Arnold, N.
AU  - Ngadjui, B.
AU  - 
VL  - 137
UR  - 
DO  - 10.1016/j.fitote.2019.104239
AB  - In the search for bioactive natural products from the African flora, three previously undescribed compounds including one stilbene-coumarin derivative (1), one coumarin-carbinol (2) and one fatty glycoside (3) were isolated from the stem bark and leaves of Monotes kerstingii, together with sixteen known compounds (4–19). The structures of the isolated compounds were elucidated based on their NMR and MS spectroscopic data and by comparison of these data with those previously reported in the literature. Compounds 1–19 were screened for anthelmintic and antimicrobial activity. None of the compounds exhibited significant anthelmintic activity. However, compounds 4, 5, 8 and 14 displayed interesting antibacterial activity against B. subtilis at a concentration of 100 μM with respective inhibition percentages of 99, 79, 71 and 100%, respectively, compared to erythromycin used as positive control. In addition, at the same concentration, compound 6 showed remarkable antifungal activity against Septoria tritici with 93.6% growth inhibition and was found to be more active than the positive controls epoconazole and terbinafine displaying 76.6 and 84.3%, respectively.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 663
TI  - New source report: Chemical constituents of Hypericum quartinianum (Hypericaceae), a sub-Saharan African plant species
JO  - Biochem. Syst. Ecol.
PY  - 2019
SP  - 46-49
AU  - Fobofou, S. A. T.
AU  - Ares, K.
AU  - Arnold, N.
AU  - Imming, P.
AU  - 
VL  - 85
UR  - 
DO  - 10.1016/j.bse.2019.05.006
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 662
TI  - Biological activity and stability analyses of knipholone anthrone, a phenyl anthraquinone derivative isolated from Kniphofia foliosa Hochst.
JO  - J. Pharm. Biomed. Anal.
PY  - 2019
SP  - 277-285
AU  - Feilcke, R.
AU  - Arnouk, G.
AU  - Raphane, B.
AU  - Richard, K.
AU  - Tietjen, I.
AU  - Andrae-Marobela, K.
AU  - Erdmann, F.
AU  - Schipper, S.
AU  - Becker, K.
AU  - Arnold, N.
AU  - Frolov, A.
AU  - Reiling, N.
AU  - Imming, P.
AU  - Fobofou, S. A. T.
AU  - 
VL  - 174
UR  - 
DO  - 10.1016/j.jpba.2019.05.065
AB  - Knipholone (1) and knipholone anthrone (2), isolated from the Ethiopian medicinal plant Kniphofia foliosa Hochst. are two phenyl anthraquinone derivatives, a compound class known for biological activity. In the present study, we describe the activity of both 1 and 2 in several biological assays including cytotoxicity against four human cell lines (Jurkat, HEK293, SH-SY5Y and HT-29), antiplasmodial activity against Plasmodium falciparum 3D7 strain, anthelmintic activity against the model organism Caenorhabditis elegans, antibacterial activity against Aliivibrio fischeri and Mycobacterium tuberculosis and anti-HIV-1 activity in peripheral blood mononuclear cells (PBMCs) infected with HIV-1c. In parallel, we investigated the stability of knipholone (2) in solution and in culture media. Compound 1 displays strong cytotoxicity against Jurkat, HEK293 and SH-SY5Y cells with growth inhibition ranging from approximately 62–95% when added to cells at 50 μM, whereas KA (2) exhibits weak to strong activity with 26, 48 and 70% inhibition of cell growth, respectively. Both 1 and 2 possess significant antiplasmodial activity against Plasmodium falciparum 3D7 strain with IC50 values of 1.9 and 0.7 μM, respectively. These results complement previously reported data on the cytotoxicity and antiplasmodial activity of 1 and 2. Furthermore, compound 2 showed HIV-1c replication inhibition (growth inhibition higher than 60% at tested concentrations 0.5, 5, 15 and 50 μg/ml and an EC50 value of 4.3 μM) associated with cytotoxicity against uninfected PBMCs. The stability study based on preincubation, HPLC and APCI-MS (atmospheric-pressure chemical ionization mass spectrometry) analysis indicates that compound 2 is unstable in culture media and readily oxidizes to form compound 1. Therefore, the biological activity attributed to 2 might be influenced by its degradation products in media including 1 and other possible dimers. Hence, bioactivity results previously reported from this compound should be taken with caution and checked if they differ from those of its degradation products. To the best of our knowledge, this is the first report on the anti-HIV activity and stability analysis of compound 2.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 661
TI  - Variation in Ceratonia siliqua pod metabolome in context of its different geographical origin, ripening stage and roasting process
JO  - Food Chem.
PY  - 2019
SP  - 675-687
AU  - Farag, M. A.
AU  - El-Kersh, D. M.
AU  - Ehrlich, A.
AU  - Choucry, M. A.
AU  - El-Seedi, H.
AU  - Frolov, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 283
UR  - 
DO  - 10.1016/j.foodchem.2018.12.118
AB  - Carob is a legume tree of a considerable commercial importance for the flavor and sweet industry. In this context, it is cultivated mostly for its pods, which are known for their nutritive value and multiple health benefits. However, metabolite patterns, underlying these properties are still mostly uncharacterized. In this study, the role of geographical origin, ontogenetic changes and thermal processing on the Ceratonia siliqua pod metabolome was assessed by mass spectrometry (MS)-based metabolomics. Thereby, a total of 70 fruits primary metabolites, represented mainly by carbohydrates, organic and amino acids were detected. Analysis of secondary bioactive metabolites assessed by ultra-high-performance liquid chromatography-electrospray ionization high resolution mass spectrometry (UHPLC-ESI-HR-MS) revealed in total 83 signals. The major signals, most significantly contributing in discrimination of C. siliqua specimens were assigned to tannins and flavonoids. PCA models derived from either UHPLC-MS or GC-MS proved to be powerful tools for discrimination of C. siliqua specimens.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 660
TI  - Sensory Metabolite Profiling in a Date Pit Based Coffee Substitute and in Response to Roasting as Analyzed via Mass Spectrometry Based Metabolomics
JO  - Molecules
PY  - 2019
SP  - 3377
AU  - Farag, M. A.
AU  - Otify, A. M.
AU  - El-Sayed, A. M.
AU  - Michel, C. G.
AU  - ElShebiney, S. A.
AU  - Ehrlich, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 24
UR  - 
DO  - 10.3390/molecules24183377
AB  - Interest in developing coffee substitutes is on the rise, to minimizing its health side effects. In the Middle East, date palm (Phoenix dactylifera L.) pits are often used as a coffee substitute post roasting. In this study, commercially-roasted date pit products, along with unroasted and home-prepared roasted date pits, were subjected to analyses for their metabolite composition, and neuropharmacological evaluation in mice. Headspace SPME-GCMS and GCMS post silylation were employed for characterizing its volatile and non-volatile metabolite profile. For comparison to roasted coffee, coffee product was also included. There is evidence that some commercial date pit products appear to contain undeclared additives. SPME headspace analysis revealed the abundance of furans, pyrans, terpenoids and sulfur compounds in roasted date pits, whereas pyrroles and caffeine were absent. GCMS-post silylation employed for primary metabolite profiling revealed fatty acids’ enrichment in roasted pits versus sugars’ abundance in coffee. Biological investigations affirmed that date pit showed safer margin than coffee from its LD50, albeit it exhibits no CNS stimulant properties. This study provides the first insight into the roasting impact on the date pit through its metabolome and its neuropharmacological aspects to rationalize its use as a coffee substitute.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 659
TI  - Influence of Pickling Process on Allium cepa and Citrus limon Metabolome as Determined via Mass Spectrometry-Based Metabolomics
JO  - Molecules
PY  - 2019
SP  - 928
AU  - Farag, M. A.
AU  - Tawfike, A. F.
AU  - Donia, M. S.
AU  - Ehrlich, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 24
UR  - 
DO  - 10.3390/molecules24050928
AB  - Brine, the historically known food additive salt solution, has been widely used as a pickling media to preserve flavor or enhance food aroma, appearance, or other qualities. The influence of pickling, using brine, on the aroma compounds and the primary and secondary metabolite profile in onion bulb Allium cepa red cv. and lemon fruit Citrus limon was evaluated using multiplex metabolomics technologies. In lemon, pickling negatively affected its key odor compound “citral”, whereas monoterpene hydrocarbons limonene and γ-terpinene increased in the pickled product. Meanwhile, in onion sulphur rearrangement products appeared upon storage, i.e., 3,5-diethyl-1,2,4-trithiolane. Profiling of the polar secondary metabolites in lemon fruit via ultra-performance liquid chromatography coupled to MS annotated 37 metabolites including 18 flavonoids, nine coumarins, five limonoids, and two organic acids. With regard to pickling impact, notable and clear separation among specimens was observed with an orthogonal projections to least squares-discriminant analysis (OPLS-DA) score plot for the lemon fruit model showing an enrichment of limonoids and organic acids and that for fresh onion bulb showing an abundance of flavonols and saponins. In general, the pickling process appeared to negatively impact the abundance of secondary metabolites in both onion and lemon, suggesting a decrease in their food health benefits.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 658
TI  - Comparative metabolome-based classification of Senna drugs: a prospect for phyto-equivalency of its different commercial products
JO  - Metabolomics
PY  - 2019
SP  - 80
AU  - Farag, M. A.
AU  - El Senousy, A. S.
AU  - El-Ahmady, S. H.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 15
UR  - 
DO  - 10.1007/s11306-019-1538-x
AB  - IntroductionThe demand to develop efficient and reliable analytical methods for the quality control of nutraceuticals is on the rise, together with an increase in the legal requirements for safe and consistent levels of its active principles.ObjectiveTo establish a reliable model for the quality control of widely used Senna preparations used as laxatives and assess its phyto-equivalency.MethodsA comparative metabolomics approach via NMR and MS analyses was employed for the comprehensive measurement of metabolites and analyzed using chemometrics.ResultsUnder optimized conditions, 30 metabolites were simultaneously identified and quantified including anthraquinones, bianthrones, acetophenones, flavonoid conjugates, naphthalenes, phenolics, and fatty acids. Principal component analysis (PCA) was used to define relative metabolite differences among Senna preparations. Furthermore, quantitative 1H NMR (qHNMR) was employed to assess absolute metabolites levels in preparations. Results revealed that 6-hydroxy musizin or tinnevellin were correlated with active metabolites levels, suggesting the use of either of these naphthalene glycosides as markers for official Senna drugs authentication.ConclusionThis study provides the first comparative metabolomics approach utilizing NMR and UPLC–MS to reveal for secondary metabolite compositional differences in Senna preparations that could readily be applied as a reliable quality control model for its analysis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 655
TI  - Two genes in a pathogenicity gene cluster encoding secreted proteins are required for appressorial penetration and infection of the maize anthracnose fungus Colletotrichum graminicola
JO  - Environ. Microbiol.
PY  - 2019
SP  - 4773-4791
AU  - Eisermann, I.
AU  - Weihmann, F.
AU  - Krijger, J.
AU  - Kröling, C.
AU  - Hause, G.
AU  - Menzel, M.
AU  - Pienkny, S.
AU  - Kiesow, A.
AU  - Deising, H. B.
AU  - Wirsel, S. G. R.
AU  - 
VL  - 21
UR  - 
DO  - 10.1111/1462-2920.14819
AB  - To avoid pathogen‐associated molecular pattern recognition, the hemibiotrophic maize pathogen Colletotrichum graminicola secretes proteins mediating the establishment of biotrophy. Targeted deletion of 26 individual candidate genes and seven gene clusters comprising 32 genes of C. graminicola identified a pathogenicity cluster (CLU5) of five co‐linear genes, all of which, with the exception of CLU5b, encode secreted proteins. Targeted deletion of all genes of CLU5 revealed that CLU5a and CLU5d are required for full appressorial penetration competence, with virulence deficiencies independent of the host genotype and organ inoculated. Cytorrhysis experiments and microscopy showed that Δclu5a mutants form pressurized appressoria, but they are hampered in forming penetration pores and fail to differentiate a penetration peg. Whereas Δclu5d mutants elicited WT‐like papillae, albeit at increased frequencies, papillae induced by Δclu5a mutants were much smaller than those elicited by the WT. Synteny of CLU5 is not only conserved in Colletotrichum spp. but also in additional species of Sordariomycetes including insect pathogens and saprophytes suggesting importance of CLU5 for fungal biology. Since CLU5a and CLU5d also occur in non‐pathogenic fungi and since they are expressed prior to plant invasion and even in vegetative hyphae, the encoded proteins probably do not act primarily as effectors.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 654
TI  - Structural diversification during glucosinolate breakdown: mechanisms of thiocyanate, epithionitrile and simple nitrile formation
JO  - Plant J.
PY  - 2019
SP  - 329-343
AU  - Eisenschmidt-Bönn, D.
AU  - Schneegans, N.
AU  - Backenköhler, A.
AU  - Wittstock, U.
AU  - Brandt, W.
AU  - 
VL  - 99
UR  - 
DO  - 10.1111/tpj.14327
AB  - Secondary metabolism is characterized by an impressive structural diversity. Here, we have addressed the mechanisms underlying structural diversification upon damage‐induced activation of glucosinolates, a group of thioglucosides found in the Brassicales. The classical pathway of glucosinolate activation involves myrosinase‐catalyzed hydrolysis and rearrangement of the aglucone to an isothiocyanate. Plants of the Brassicaceae possess specifier proteins, i.e. non‐heme iron proteins that promote the formation of alternative products by interfering with this reaction through unknown mechanisms. We have used structural information available for the thiocyanate‐forming protein from Thlaspi arvense (TaTFP), to test the impact of loops protruding at one side of its β‐propeller structure on product formation using the allylglucosinolate aglucone as substrate. In silico loop structure sampling and semiempirical quantum mechanical calculations identified a 3L2 loop conformation that enabled the Fe2+ cofactor to interact with the double bond of the allyl side chain. Only this arrangement enabled the formation of allylthiocyanate, a specific product of TaTFP. Simulation of 3,4‐epithiobutane nitrile formation, the second known product of TaTFP, required an alternative substrate docking arrangement in which Fe2+ interacts with the aglucone thiolate. In agreement with these results, substitution of 3L2 amino acid residues involved in the conformational change as well as exchange of critical amino acid residues of neighboring loops affected the allylthiocyanate versus epithionitrile proportion obtained upon myrosinase‐catalyzed allylglucosinolate hydrolysis in the presence of TaTFP in vitro. Based on these insights, we propose that specifier proteins are catalysts that might be classified as Fe2+‐dependent lyases.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 653
TI  - Impact of the mesoporous silica SBA-15 functionalization on the mode of action of Ph3Sn(CH2)6OH
JO  - Mater. Sci. Eng. C-Mater. Biol. Appl.
PY  - 2019
SP  - 315-322
AU  - Edeler, D.
AU  - Drača, D.
AU  - Petković, V.
AU  - Natalio, F.
AU  - Maksimović-Ivanić, D.
AU  - Mijatović, S.
AU  - Schmidt, H.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 100
UR  - 
DO  - 10.1016/j.msec.2019.03.010
AB  - Herein appropriateness of nonfunctionalized mesoporous silica nanoparticles SBA-15 and functionalized with (3-chloropropyl)triethoxysilane (→ SBA-15~Cl) and (3-aminopropyl)triethoxysilane (→ SBA-15~NH2) on delivery of physically adsorbed Ph3Sn(CH2)6OH (Sn6) is evaluated. Fluorescent nanomaterial, bearing isatoic moiety, loaded with Sn6 (→ SBA-15~NF&#124;Sn6) was used for cellular uptake study. The fluorescent nanomaterial is efficiently acquired and distributed into the cytoplasm of the cells even after 2 h of cultivation. According to the attained data, all SBA-15 materials loaded with Sn6 diminished cellular viability in dose dependent manner while carriers alone (SBA-15, SBA-15~Cl, SBA-15~NH2) did not show cytotoxicity against B16 cells. According to the MC50 values structural modification of SBA-15 did not improve the efficacy of tested drug. While progressive apoptosis was detected upon the treatment with SBA-15&#124;Sn6, exposure of cells to SBA-15~NH2&#124;Sn6 revealed extinguished apoptosis in time, accompanied with lower caspase activity. This effect is probably due to triggered autophagic process under the treatment with the SBA-15~NH2&#124;Sn6, thus opposed to apoptosis. Presented results suggested that functionalization of SBA-15 was not beneficial for the efficacy of loaded drug, thus, all of them are almost equally efficient considering loaded Sn6 content. Importantly, functionalization of SBA-15 does have an influence on the mode of action and differentiation inducing properties.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 652
TI  - Iridoids and volatile pheromones of Tapinoma darioi ants: chemical differences to the closely related species Tapinoma magnum
JO  - Chemoecology
PY  - 2019
SP  - 51-60
AU  - D’Eustacchio, D.
AU  - Centorame, M.
AU  - Fanfani, A.
AU  - Senczuk, G.
AU  - Jiménez-Alemán, G. H.
AU  - Vasco-Vidal, A.
AU  - Méndez, Y.
AU  - Ehrlich, A.
AU  - Wessjohann, L.
AU  - Francioso, A.
AU  - 
VL  - 29
UR  - 
DO  - 10.1007/s00049-018-00275-9
AB  - Tapinoma species, and more general dolichoderine ants, are able to produce a variety of volatile compounds they use as chemical defense, alarm, and communication pheromones. Among these, iridoids and volatile ketones are the predominant molecule classes produced by the anal glands of these ants. A recent taxonomic revision of the genus Tapinoma in Europe revealed that the supercolonial species Tapinoma nigerrimum consists of a complex of four cryptic species. Two of them, Tapinoma magnum and the newly described Tapinoma darioi, are closely related species that evolutionary diverged recently. In this work, we determine and characterize the chemical profile of pheromones and volatile compounds of two Tapinoma species. From a chemical point of view, T. darioi and T. magnum show both qualitative and quantitative differences in the pheromones produced, supporting the taxonomic revision of the T. nigerrimum complex. Our data confirm T. darioi and T. magnum as separate species also from a biochemical point of view demonstrating the value of chemotaxonomy as a suitable tool for integrative studies of species differentiation even for closely related taxa.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 650
TI  - The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model
JO  - Exp. Cell Res.
PY  - 2019
SP  - 159-170
AU  - Drača, D.
AU  - Mijatović, S.
AU  - Krajnović, T.
AU  - Pristov, J. B.
AU  - Đukić, T.
AU  - Kaluđerović, G. N.
AU  - Wessjohann, L. A.
AU  - Maksimović-Ivanić, D.
AU  - 
VL  - 380
UR  - 
DO  - 10.1016/j.yexcr.2019.04.028
AB  - Synthetic tubugis are equally potent but more stable than their natural forms. Their anticancer potential was estimated on a solid melanoma in vitro and in vivo. Tubugi-1 induced the apoptosis in B16 cells accompanied with strong intracellular production of reactive species, subsequently imposing glutathione and thiol group depletion. Paradoxically, membrane lipids were excluded from the cascade of intracellular oxidation, according to malondialdehyde decrease. Although morphologically apoptosis was typical, externalization of phosphatidylserine (PS) as an early apoptotic event was not detected. Even their exposition is pivotal for apoptotic cell eradication, primary macrophages successfully eliminated PS-deficient tubugi-1 induced apoptotic cells. The tumor volume in animals exposed to the drug in therapeutic mode was reduced in comparison to control as well as to paclitaxel-treated animals. Importantly, macrophages isolated from tubugi-1 treated animals possessed conserved phagocytic activity and were functionally and phenotypically recognized as M1. The cytotoxic effect of tubugi-1 is accomplished through its ability to polarize the macrophages toward M1, probably by PS independent apoptotic cell engulfment. The unique potential of tubugi-1 to prime the innate immune response through the induction of a specific pattern of tumor cell apoptosis can be of extraordinary importance from fundamental and applicable aspects.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 649
TI  - Synthetic Tubulysin Derivative, Tubugi-1, Against Invasive Melanoma Cells: The Cell Death Triangle
JO  - Anticancer Res.
PY  - 2019
SP  - 5403-5415
AU  - Drača, D.
AU  - Mijatović, S.
AU  - Krajnović, T.
AU  - Kaluđerović, G. N.
AU  - Wessjohann, L. A.
AU  - Maksimović-Ivanić, D.
AU  - 
VL  - 39
UR  - 
DO  - 10.21873/anticanres.13734
AB  - Background/Aim: Tubugi-1 is a more stable and accessible synthetic counterpart of natural tubulysins. This study aimed to evaluate its cytotoxic potential against anaplastic human melanoma cells. Materials and Methods: The viability of A-375 cells was determined by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assay. The type of cell death and proliferative rate were investigated using flow cytometry and fluorescent microscopy, while the molecular background was evaluated by western blot. Results: Tubugi-1 reduced the viability of A-375 cells, inducing massive micronucleation, followed by augmented expression of inhibitor of nuclear factor-κB and caspase-2, typical of a mitotic catastrophe. Disturbed proliferation and G2M block with prominent caspase activity, weakened the expression of B-cell lymphoma 2 and B-cell lymphoma 2-associated X transient up-regulation, coexisted with intensive autophagy. Specific inhibition of autophagy by chloroquine resulted in conversion from mitotic catastrophe to rapid apoptosis. Conclusion: Multilevel anticancer action of tubugi-1 is extended by co-application of an autophagy inhibitor, giving a new dimension in further preclinical advancement of this potential agent.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 645
TI  - Coenzyme A‐Conjugated Cinnamic Acids – Enzymatic Synthesis of a CoA‐Ester Library and Application in Biocatalytic Cascades to Vanillin Derivatives
JO  - Adv. Synth. Catal.
PY  - 2019
SP  - 5346-5350
AU  - Dippe, M.
AU  - Bauer, A.-K.
AU  - Porzel, A.
AU  - Funke, E.
AU  - Müller, A. O.
AU  - Schmidt, J.
AU  - Beier, M.
AU  - Wessjohann, L. A.
AU  - 
VL  - 361
UR  - 
DO  - 10.1002/adsc.201900892
AB  - We present a bioorthogonal method for the ligation of coenzyme A (CoA) with cinnamic acids. The reaction, which is the initial step in the biosynthesis of a multitude of bioactive secondary metabolites, is catalyzed by a promiscuous plant ligase and yields CoA conjugates with different functionalization in high purity and without formation of by‐products. Its applicability in biosynthetic cascades is shown for the direct transformation of cinnamic acids into natural benzaldehydes (like vanillin) or artificial derivatives (e. g. ethylvanillin).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 643
TI  - New compounds of Siolmatra brasiliensis and inhibition of in vitro protein glycation damage
JO  - Fitoterapia
PY  - 2019
SP  - 109-119
AU  - Corrêa dos Santos, C. H.
AU  - Talpo, T. C.
AU  - Pereira Motta, B.
AU  - Kiyoshi Kaga, A.
AU  - Martins Baviera, A.
AU  - Nora Castro, R.
AU  - da Silva, V. C.
AU  - Teixeira de Sousa-Junior, P.
AU  - Wessjohann, L.
AU  - Geraldo de Carvalho, M.
AU  - 
VL  - 133
UR  - 
DO  - 10.1016/j.fitote.2018.12.023
AB  - Twenty compounds were isolated from the hydroethanolic extract of the stems of Siolmatra brasiliensis, five flavonoids, two lignans, one glucosyl phytosterol, seven nor-cucurbitacins, one new phenolic derivative named siolmatrin (1) and four new dammarane-type saponins named siolmatrosides II-V (2–5), the structures of the compounds were assigned by means of 1D and 2D NMR experiments and HRESIMS of the natural compounds and some acetyl derivatives. The effects of the crude hydroethanolic extract (SbExt) and the ethyl acetate fraction (SbEtAc) of Siolmatra brasiliensis stems on the formation of advanced glycation end-products (AGEs) were also investigated. In the in vitro model system of protein glycation using bovine serum albumin (BSA) and glucose, addition of SbExt or SbEtAc inhibited the formation of fluorescent AGEs, in parallel to minor levels of fructosamine (SbEtAc) and markers of tyrosine and tryptophan oxidation (SbExt and SbEtAc). Protein crosslinking, which represents changes of late stages of protein glycation, was reduced in the presence of SbExt and SbEtAc. Siolmatra brasiliensis stems seem to be a promising source of compounds having ability to prevent glycoxidation changes, arising as an interesting option to be studied as a complementary therapy for complications of diabetes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 642
TI  - Dammarane-type triterpenoids from the stem of Ziziphus glaziovii Warm. (Rhamnaceae)
JO  - Phytochemistry
PY  - 2019
SP  - 250-259
AU  - Corrêa dos Santos, C. H.
AU  - Geraldo de Carvalho, M.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - 
VL  - 162
UR  - 
DO  - 10.1016/j.phytochem.2019.03.010
AB  - Seven undescribed dammarane-type triterpenoids, together with ten known compounds, were isolated from the stems of Ziziphus glaziovii Warm (= Sarcomphalus glaziovii (Warm.) Hauenschild). The structures were fully assigned by means of uni- and bidimensional NMR and HR-ESI-MS experiments. Extract, fractions and also isolated compounds were evaluated for their antibacterial (against Bacillus subtilis and Aliivibrio fischeri), cytotoxic (against PC-3 and HT-29 human cancer cell lines), anthelmintic (against Caenorhabditis elegans) and antifungal (against Septoria triciti, Botrytis cinerea and Phytopthoria infestans) activities. The methanolic crude extract exhibited substantial antibacterial and cytotoxic activity. The known triterpenes epigouanic acid and alphitolic acid were the most active compounds against B. subtilis, with IC50 of 12 and 22 μM, respectively. The isolated compounds presented up to a concentration of 10 μM none or only weak effects in the cytotoxicity assays. No anthelminthic and antifungal activities were observed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 641
TI  - Rhodiola rosea root extract has antipsychotic-like effects in rodent models of sensorimotor gating
JO  - J. Ethnopharmacol.
PY  - 2019
SP  - 320-328
AU  - Coors, A.
AU  - Brosch, M.
AU  - Kahl, E.
AU  - Khalil, R.
AU  - Michels, B.
AU  - Laub, A.
AU  - Franke, K.
AU  - Gerber, B.
AU  - Fendt, M.
AU  - 
VL  - 235
UR  - 
DO  - 10.1016/j.jep.2019.02.031
AB  - Ethnopharmacological relevanceThe plant arctic root (Rhodiola rosea, L.) is growing in northern regions of Europe, Asia and North America. Extracts of R. rosea are used in traditional medicine for various conditions related to nervous system function. According to scientific studies from the last decades, the plant might have potential for use in the treatment of memory impairments, stress and depression, but reports concerning other neuropsychiatric disorders are scarce.Aim of the studyIn this context, our study aimed to examine potential antipsychotic-like effects of R. rosea root extract.Materials and MethodsWe tested the effects of R. rosea root extract on prepulse inhibition in rats and mice. Prepulse inhibition is an established operational measure of sensorimotor gating, which is impaired in schizophrenia and other psychotic disorders.ResultsR. rosea root extract increased prepulse inhibition in rats and mice. Interestingly, the R. rosea extract had stronger effects in those individual animals that had low baseline levels of prepulse inhibition. Therefore, we performed further experiments in which we pharmacologically induced a prepulse inhibition deficit by two different psychostimulants, either the dopamine D2 receptor agonist apomorphine or the NMDA receptor antagonist dizocilpine (MK-801). Pre-treatment with the R. rosea extract significantly restored both, apomorphine- and dizocilpine-induced prepulse inhibition deficits.ConclusionsThe present study demonstrates that R. rosea extract robustly reverses prepulse inhibition deficits in rodents. This suggests antipsychotic-like effects of R. rosea extract. Future studies should focus on the pharmacological mechanisms underlying these effects.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 638
TI  - 3D-clinorotation induces specific alterations in metabolite profiles of germinating Brassica napus L. seeds
JO  - Biol. Commun.
PY  - 2019
SP  - 55-74
AU  - Chantseva, V.
AU  - Bilova, T.
AU  - Smolikova, G.
AU  - Frolov, A.
AU  - Medvedev, S.
AU  - 
VL  - 64
UR  - 
DO  - 10.21638/spbu03.2019.107
AB  - During the whole history of their life on Earth, higher plants evolved under the constant gravity stimulus. Therefore, plants developed efficient mechanisms of gravity perception, underlying their ability to adjust the direction of growth to the gravity vector, i.e. the phenomenon of gravitropism. In this context, alterations in the magnitude and vector of the gravity field might compromise plant growth and development. This aspect was successfully addressed in gravity fields of low intensity (microgravity). On the other hand, microgravity can be simulated on the Earth by clinorotation, i.e. rotation of the experimental plant along one or several axes. This approach is routinely used for studies of gravity-related responses of crop plants, although the effect of simulated microgravity on the most sensitive ontogenetic stages — germination and seedling development — is still not sufficiently characterized. Recently, we addressed the effects of clinorotation on the proteome of germinating oilseed rape (Brassica napus) seeds. Here we extend this study to the seedling primary metabolome and address its changes in the presence of 3D-clinorotation. GC-MS analysis revealed essential alterations in patterns of sugars and sugar phosphates (specifically glucose-6-phosphate), methionine and glycerol. Thereby, abundances of individual metabolites showed high dispersion, indicating high lability and plasticity of the seedling metabolome.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 637
TI  - Age-related ultrastructural changes of the basement membrane in the mouse blood-brain barrier
JO  - J. Cell. Mol. Med.
PY  - 2019
SP  - 819-827
AU  - Ceafalan, L. C.
AU  - Fertig, T. E.
AU  - Gheorghe, T. C.
AU  - Hinescu, M. E.
AU  - Popescu, B. O.
AU  - Pahnke, J.
AU  - Gherghiceanu, M.
AU  - 
VL  - 23
UR  - 
DO  - 10.1111/jcmm.13980
AB  - The blood‐brain barrier (BBB) is essential for a functional neurovascular unit. Most studies focused on the cells forming the BBB, but very few studied the basement membrane (BM) of brain capillaries in ageing. We used transmission electron microscopy and electron tomography to investigate the BM of the BBB in ageing C57BL/6J mice. The thickness of the BM of the BBB from 24‐month‐old mice was double as compared with that of 6‐month‐old mice (107 nm vs 56 nm). The aged BBB showed lipid droplets gathering within the BM which further increased its thickness (up to 572 nm) and altered its structure. The lipids appeared to accumulate toward the glial side of the BM. Electron tomography showed that the lipid‐rich BM regions are located in small pockets formed by the end‐feet of astrocytes. These findings suggest an imbalance of the lipid metabolism and that may precede the structural alteration of the BM. These alterations may favour the accretion of abnormal proteins that lead to neurodegeneration in ageing. These findings warrant further investigation of the BM of brain capillaries and of adjoining cells as potential targets for future therapies.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 636
TI  - Multicomponent synthesis of α-acylamino and α-acyloxy amide derivatives of desmycosin and their activity against gram-negative bacteria
JO  - Bioorg. Med. Chem.
PY  - 2019
SP  - 3237-3247
AU  - Budragchaa, T.
AU  - Westermann, B.
AU  - Wessjohann, L. A.
AU  - 
VL  - 27
UR  - 
DO  - 10.1016/j.bmc.2019.05.046
AB  - Bacterial resistance to the existing drugs requires constant development of new antibiotics. Developing compounds active against gram-negative bacteria thereby is one of the more challenging tasks. Among the many approaches to develop successful antibacterials, medicinal chemistry driven evolution of existing successful antibiotics is considered to be the most effective one. Towards this end, the C-20 aldehyde moiety of desmycosin was modified into α-acylamino and α-acyloxy amide functionalities using isonitrile-based Ugi and Passerini reactions, aiming for enhanced antibacterial and physicochemical properties. The desired compounds were obtained in 45–93% yield under mild conditions. The antibacterial activity of the resulting conjugates was tested against gram-negative Aliivibrio fischeri. The antibiotic strength is mostly governed by the amine component introduced. Thus, methylamine derived desmycosin bis-amide 4 displayed an enhanced inhibition rate vs. desmycosin (99% vs. 83% at 1 µM). Derivatives with long acyclic or bulky amine and isocyanide Ugi components reduced potency, whereas carboxylic acid reagents with longer chain length afforded increased bioactivity. In Passerini 3-component products, the butyric ester amide 22 displayed a higher activity (90% at 1 µM) than the mother compound desmycosin (2).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 629
TI  - CYP76 Oxidation Network of Abietane Diterpenes in Lamiaceae Reconstituted in Yeast
JO  - J. Agr. Food Chem.
PY  - 2019
SP  - 13437-13450
AU  - Bathe, U.
AU  - Frolov, A.
AU  - Porzel, A.
AU  - Tissier, A.
AU  - 
VL  - 67
UR  - 
DO  - 10.1021/acs.jafc.9b00714
AB  - Rosemary and sage species from Lamiaceae contain high amounts of structurally related but diverse abietane diterpenes. A number of substances from this compound family have potential pharmacological activities and are used in the food and cosmetic industry. This has raised interest in their biosynthesis. Investigations in Rosmarinus officinalis and some sage species have uncovered two main groups of cytochrome P450 oxygenases that are involved in the oxidation of the precursor abietatriene. CYP76AHs produce ferruginol and 11-hydroxyferruginol, while CYP76AKs catalyze oxidations at the C20 position. Using a modular Golden-Gate-compatible assembly system for yeast expression, these enzymes were systematically tested either alone or in combination. A total of 14 abietane diterpenes could be detected, 8 of which have not been reported thus far. We demonstrate here that yeast is a valid system for engineering and reconstituting the abietane diterpene network, allowing for the discovery of novel compounds with potential bioactivity.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 628
TI  - Analysis of Chemically Labile Glycation Adducts in Seed Proteins: Case Study of Methylglyoxal-Derived Hydroimidazolone 1 (MG-H1)
JO  - Int. J. Mol. Sci.
PY  - 2019
SP  - 3659
AU  - Antonova, K.
AU  - Vikhnina, M.
AU  - Soboleva, A.
AU  - Mehmood, T.
AU  - Heymich, M.-L.
AU  - Leonova, T.
AU  - Bankin, M.
AU  - Lukasheva, E.
AU  - Gensberger-Reigl, S.
AU  - Medvedev, S.
AU  - Smolikova, G.
AU  - Pischetsrieder, M.
AU  - Frolov, A.
AU  - 
VL  - 20
UR  - 
DO  - 10.3390/ijms20153659
AB  - Seeds represent the major source of food protein, impacting on both human nutrition and animal feeding. Therefore, seed quality needs to be appropriately addressed in the context of viability and food safety. Indeed, long-term and inappropriate storage of seeds might result in enhancement of protein glycation, which might affect their quality and longevity. Glycation of seed proteins can be probed by exhaustive acid hydrolysis and quantification of the glycation adduct Nɛ-(carboxymethyl)lysine (CML) by liquid chromatography-mass spectrometry (LC-MS). This approach, however, does not allow analysis of thermally and chemically labile glycation adducts, like glyoxal-, methylglyoxal- and 3-deoxyglucosone-derived hydroimidazolones. Although enzymatic hydrolysis might be a good solution in this context, it requires aqueous conditions, which cannot ensure reconstitution of seed protein isolates. Because of this, the complete profiles of seed advanced glycation end products (AGEs) are not characterized so far. Therefore, here we propose the approach, giving access to quantitative solubilization of seed proteins in presence of sodium dodecyl sulfate (SDS) and their quantitative enzymatic hydrolysis prior to removal of SDS by reversed phase solid phase extraction (RP-SPE). Using methylglyoxal-derived hydroimidazolone 1 (MG-H1) as a case example, we demonstrate the applicability of this method for reliable and sensitive LC-MS-based quantification of chemically labile AGEs and its compatibility with bioassays.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 627
TI  - Phytochemical Isolation and Biological Activities of Corydalis adiantifolia from Baltistan
JO  - J. Chem. Soc. Pakistan
PY  - 2019
SP  - 535-543
AU  - Ali, I.
AU  - Ali, Z.
AU  - Zamarrud, A.
AU  - Hussain, H.
AU  - Ahmad, V. U.
AU  - 
VL  - 41
UR  - 
AB  - The whole plant material of Corydalis adiantifolia Hook.f. &amp; Thomson was investigated for biological activities e.g. antifungal, antibacterial, insecticidal, cytotoxic, anticancer and phytotoxic activities and preliminary phytochemical screening. The methanol extract and dichloromethane fraction of the plant species exhibited 5% inhibition each against the fungus Aspergillus flavus. The methanol extract and water and dichloromethane fractions exhibited non-significant antibacterial activity and they showed inhibition against Hela cell lines and insignificant insecticidal activity. To understand the bioactive profile of C. adiantifolia, phytochemical screening approach is considered effective. The samples including methanol extract and n-hexane, dichloromethane, ethyl acetate and water fractions were subjected to qualitative phytochemical screening for the presence of various phytochemicals i.e. alkaloids, flavonoids, saponins, diterprenes, triterpenoids, anthraquinones, anthranol glycosides, reducing sugars and phenols. The results exhibited the efficacy of methanol extract showing the presence of more phytochemicals in comparison to the fractions of C. adiantifolia. Moreover, as a result of phytochemical isolation, 8-acetonyldihydrosanguinarine (1), β-sitosterol (2) and β-sitosterol-β-D-glucoside (3) were isolated, purified, and characterized by spectroscopic methods. To the best of our knowledge, all this study was carried out for the first time on C. adiantifolia.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 626
TI  - Isolation of Phytochemical Constituents from Hunteria umbellata K. Schum
JO  - Trop. J. Nat. Prod. Res.
PY  - 2019
SP  - 95-98
AU  - Ali, I.
AU  - Falodun, A.
AU  - Siyo, B.
AU  - Jules, B. K. J.
AU  - Hussain, H.
AU  - Langer, P.
AU  - 
VL  - 3
UR  - 
DO  - 10.26538/tjnpr/v3i3.6
AB  - Hunteria umbellata K. Schum has been reported for the treatment of diabetes in Nigeria. In the present study, the ethanolic extract of dried leaves of Hunteria umbellata K. Schum was investigated for the chemical principles. The isolated pure compounds were characterized by NMR, IR and Mass spectral studies. Ursolic acid (1), oleanolic acid (2) and squalene (3) were the main constituents isolated from the extract.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 625
TI  - The management of diabetes mellitus-imperative role of natural products against dipeptidyl peptidase-4, α-glucosidase and sodium-dependent glucose co-transporter 2 (SGLT2)
JO  - Bioorg. Chem.
PY  - 2019
SP  - 305-315
AU  - Abbas, G.
AU  - Al Harrasi, A.
AU  - Hussain, H.
AU  - Hamaed, A.
AU  - Supuran, C. T.
AU  - 
VL  - 86
UR  - 
DO  - 10.1016/j.bioorg.2019.02.009
AB  - Diabetes mellitus is a chronic metabolic disorder which is rapidly spreading worldwide. It is characterized by persistent elevated blood glucose level above normal values (hyperglycemia) due to defect in either insulin secretion or in insulin action or both of them. Currently approved oral synthetic antidiabetic drugs such as biguanides, thiazolidinediones, sulfonylureas, and meglitinides have shown undesirable side effects. Therefore, newer approaches and targets for the management of diabetes mellitus are highly desirable. Dipeptidyl peptidase-4 enzyme, α-glucosidase enzyme and sodium-dependent glucose co-transporter 2 (SGLT2) have been recognized as effective therapeutic targets for the management of diabetes mellitus while natural products are alternatives to oral synthetic hypoglycemic agents. During the last two decades, many researchers were working on the identification and the validation of plant-derived products for curing various diseases. Natural products do not only provide useful drugs in their own right but also provide templates for the development of more effective compounds for enhanced therapeutic potential. Herein, we advocated the vital role of natural products as source of new drugs by presenting promising inhibitors of dipeptidyle peptidase-4 enzyme, α-glucosidase enzyme and (SGLT2) obtained from different medicinal plants as potential candidates for drug development against diabetes mellitus. The structure–activity relationship (SAR) of these various inhibitors is also discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 33
TI  - Ion Homeostasis Response to Nutrient-Deficiency Stress in Plants
T2  - Cell Growth
PB  - 
PY  - 2019
SP  - 1-23
AU  - Osmolovskaya, N.
AU  - Shumilina, J.
AU  - Bureiko, K.
AU  - Chantseva, V.
AU  - Bilova, T.
AU  - Kuchaeva, L.
AU  - Laman, N.
AU  - Wessjohann, L. A.
AU  - Frolov, A.
AU  - 
VL  - 
UR  - 
SN  - 978-1-78985-311-7
DO  - 10.5772/intechopen.89398
AB  - A crucial feature of plant performance is its strong dependence on the availability of essential mineral nutrients, affecting multiple vital functions. Indeed, mineral-nutrient deficiency is one of the major stress factors affecting plant growth and development. Thereby, nitrogen and potassium represent the most abundant mineral contributors, critical for plant survival. While studying plant responses to nutrient deficiency, one should keep in mind that mineral nutrients, along with their specific metabolic roles, are directly involved in maintaining cell ion homeostasis, which relies on a finely tuned equilibrium between cytosolic and vacuolar ion pools. Therefore, in this chapter we briefly summarize the role of the ion homeostasis system in cell responses to environmental deficiency of nitrate and potassium ions. Special attention is paid to the implementation of plant responses via NO3− and K+ root transport and regulation of ion distribution in cell compartments. These responses are strongly dependent on plant species, as well as severity and duration of nutrient deficiency.
A2  - Vikas, B. &amp; Fasullo, M., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 26
TI  - Recent Progress of Phenazines as Anticancer Agents
T2  - 
PB  - Top. Anti-Cancer Res.
PY  - 2019
SP  - 74-96
AU  - Hussain, H.
AU  - Ur Rehman, N.
AU  - Abbas, G.
AU  - Khattak, K. F.
AU  - Khan, A.
AU  - Green, I. R.
AU  - 
VL  - 8
UR  - 
SN  - 978-981-14-0438-2
DO  - 10.2174/9789811404382119080006
AB  - Phenazines are nitrogen-containing heterocycles which possess a wide range of biological activities and in particular, cytotoxic effects. Moreover, various phenazines have been prepared having alkyl, amide, carboxylic acid, aldehyde, and pyrano groups. These synthetic phenazines possess significant anticancer effects towards various cancers. On the other hand, only a few natural phenazines have been reported with anticancer effects. This chapter presents a comprehensive overview of the most recent patents related to the phenazines as anticancer agents.
A2  - Atta-ur-Rahman &amp; Zaman, K., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 25
TI  - Fungal Polyketides: Chemical Diversity and Their Cytotoxic Effects
T2  - Biodiversity and Chemotaxonomy
PB  - Sustain. Dev. Biodivers.
PY  - 2019
SP  - 195-214
AU  - Hussain, H.
AU  - Schulz, B.
AU  - Green, I. R.
AU  - 
VL  - 24
UR  - 
SN  - 978-3-030-30746-2
DO  - 10.1007/978-3-030-30746-2_9
AB  - Compounds isolated from different natural sources have over the years played crucial roles in the treatment of a wide range of human diseases. Over the past six decades, microorganisms have provided valuable active compounds for the treatment of various diseases. Fungi, in general, produce diverse structural classes of natural products including polyketides, a major class of secondary metabolites obtained from various natural sources‚ which as a group have interesting chemical diversity. In addition, polyketides are known to possess a number of biological and pharmacological effects, viz. cytotoxic, antibacterial, antifungal, antiparasitic, and immunosuppressive effects. In this chapter the focus is on describing the cytotoxic effects of polyketides isolated from fungi and in particular their potential as cancerostatic pharmaceuticals.
A2  - Ramawat, K. G., ed.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 22
TI  - Thiotaurine: From Chemical and Biological Properties to Role in H2S Signaling
T2  - Taurine 11
PB  - Adv. Exp. Med. Biol.
PY  - 2019
SP  - 755-771
AU  - Baseggio Conrado, A.
AU  - Capuozzo, E.
AU  - Mosca, L.
AU  - Francioso, A.
AU  - Fontana, M.
AU  - 
VL  - 1155
UR  - 
SN  - 978-981-13-8023-5
DO  - 10.1007/978-981-13-8023-5_66
AB  - In the last decade thiotaurine, 2-aminoethane thiosulfonate, has been investigated as an inflammatory modulating agent as a result of its ability to release hydrogen sulfide (H2S) known to play regulatory roles in inflammation. Thiotaurine can be included in the “taurine family” due to structural similarity to taurine and hypotaurine, and is characterized by the presence of a sulfane sulfur moiety. Thiotaurine can be produced by different pathways, such as the spontaneous transsulfuration between thiocysteine – a persulfide analogue of cysteine – and hypotaurine as well as in vivo from cystine. Moreover, the enzymatic oxidation of cysteamine to hypotaurine and thiotaurine in the presence of inorganic sulfur can occur in animal tissues and last but not least thiotaurine can be generated by the transfer of sulfur from mercaptopyruvate to hypotaurine catalyzed by a sulfurtransferase. Thiotaurine is an effective antioxidant agent as demonstrated by its ability to counteract the damage caused by pro-oxidants in the rat. Recently, we observed the influence of thiotaurine on human neutrophils functional responses. In particular, thiotaurine has been found to prevent human neutrophil spontaneous apoptosis suggesting an alternative or additional role to its antioxidant activity. It is likely that the sulfane sulfur of thiotaurine may modulate neutrophil activation via persulfidation of target proteins. In conclusion, thiotaurine can represent a biologically relevant sulfur donor acting as a biological intermediate in the transport, storage and release of sulfide.
A2  - Hu, J., et al., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2535
TI  - Methodology of Drought Stress Research: Experimental Setup and Physiological Characterization
JO  - Preprints
PY  - 2018
SP  - 
AU  - Osmolovskaya, N.
AU  - Shumilina, J.
AU  - Kim, A.
AU  - Didio, A.
AU  - Grishina, T.
AU  - Bilova, T.
AU  - Keltsieva, O. A.
AU  - Zhukov, V.
AU  - Tikhonovich, I.
AU  - Tarakhovskaya, E.
AU  - Wessjohann, L. A.
AU  - Frolov, A.
AU  - 
VL  - 
UR  - 
DO  - 10.20944/preprints201812.0145.v1
AB  - Drought is one of the major stress factors affecting growth and development of plants. In this context, drought-related losses of crop plant productivity impede sustainable agriculture all over the world. In general, plants responses to water deficit by multiple physiological and metabolic adaptations at the molecular, cellular and organism levels. To understand the underlying mechanisms of drought tolerance, adequate stress models and arrays of reliable stress markers are required. Therefore, in this review we comprehensively address currently available models of drought stress, based on culturing plants in soil, hydroponic or agar culture. These experimental setups give access to different aspects of plant response to drought, like decrease of tissue water potential, reduction of stomata conductance and photosynthesis efficiency, accumulation of low-molecular weight solutes (metabolic adjustment) and drought protective proteins. Till now, this pattern of markers was successfully extended to the methods of enzyme chemistry, molecular biology and omics techniques. Thus, conventional tests can be efficiently complemented by determination of phytohormone and reactive oxygen species (ROS) contents, activities of antioxidant enzymes, as well as comprehensive profiling of transcriptome, proteome and metabolome.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2531
TI  - Proteome Map of Pea (Pisum Sativum L.) Embryos Containing Different Amounts of Residual Chlorophylls
JO  - Preprints
PY  - 2018
SP  - 
AU  - Mamontova, T.
AU  - Lukasheva, E.
AU  - Mavropolo-Stolyarenko, G.
AU  - Proksch, C.
AU  - Bilova, T.
AU  - Kim, A.
AU  - Babakov, V.
AU  - Grishina, T.
AU  - Hoehenwarter, W.
AU  - Medvedev, S.
AU  - Smolikova, G.
AU  - Frolov, A.
AU  - 
VL  - 
UR  - 
DO  - 10.20944/preprints201812.0069.v1
AB  - Due to low culturing costs and high seed protein contents, legumes represent the main global source of food protein. Pea (Pisum sativum L.) is one of the major economically important legume crops, impacting both animal feed and human nutrition. Therefore, the quality of pea seeds needs to be ensured in the context of sustainable crop production and nutritional efficiency. Obviously, changes in seed protein patterns might directly affect both of these aspects. Thus, here we address the pea seed proteome in more detail and provide, to the best of our knowledge, the most comprehensive annotation of the functions and intracellular localization of pea seed proteins. Accordingly, 1938 and 1989 non-redundant proteins were identified in yellow and green pea seeds, in total. Only 35 and 44 proteins, respectively, could be additionally identified after protamine sulfate precipitation (PSP) potentially indicating the high efficiency of our experimental workflow. In total 981 protein groups could be assigned to 34 functional classes, which were to a large extent differentially represented in yellow and green seeds. Closer analysis of these differences by processing of the data in KEGG and String databases revealed their possible relation to a higher metabolic status and reduced longevity of green seeds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 799
TI  - Drug Delivery System for Emodin Based on Mesoporous Silica SBA-15
JO  - Nanomaterials
PY  - 2018
SP  - 322
AU  - Krajnović, T.
AU  - Maksimović-Ivanić, D.
AU  - Mijatović, S.
AU  - Drača, D.
AU  - Wolf, K.
AU  - Edeler, D.
AU  - Wessjohann, L.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 8
UR  - 
DO  - 10.3390/nano8050322
AB  - In this study mesoporous silica SBA-15 was evaluated as a vehicle for the transport of cytotoxic natural product emodin (EO). SBA-15 was loaded with different quantities of EO (SBA-15&#124;EO1–SBA-15&#124;EO5: 8–36%) and characterized by traditional methods. Several parameters (stabilities) and the in vitro behavior on tumor cell lines (melanoma A375, B16 and B16F10) were investigated. SBA-15 suppresses EO release in extremely acidic milieu, pointing out that EO will not be discharged in the stomach. Furthermore, SBA-15 protects EO from photodecomposition. In vitro studies showed a dose dependent decrease of cellular viability which is directly correlated with an increasing amount of EO in SBA-15 for up to 27% of EO, while a constant activity for 32% and 36% of EO in SBA-15 was observed. Additionally, SBA-15 loaded with EO (SBA-15&#124;EO3) does not disturb viability of peritoneal macrophages. SBA-15&#124;EO3 causes inhibition of tumor cell proliferation and triggers apoptosis, connected with caspase activation, upregulation of Bax, as well as Bcl-2 and Bim downregulation along with amplification of poly-(ADP-ribose)-polymerase (PARP) cleavage fragment. Thus, the mesoporous SBA-15 is a promising carrier of the water-insoluble drug emodin.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 792
TI  - Therapeutic potential of glycyrrhetinic acids: a patent review (2010-2017)
JO  - Expert Opin. Ther. Pat.
PY  - 2018
SP  - 383-398
AU  - Hussain, H.
AU  - Green, I. R.
AU  - Shamraiz, U.
AU  - Saleem, M.
AU  - Badshah, A.
AU  - Abbas, G.
AU  - Rehman, N. U.
AU  - Irshad, M.
AU  - 
VL  - 28
UR  - 
DO  - 10.1080/13543776.2018.1455828
AB  - Introduction: Glycyrrhetinic acids (GAs) viz., 18β-glycyrrhetinic acid and 18α-glycyrrhetinic acid, are oleanane-type triterpenes having a carboxylic acid group at C-30, and are extracted from the Chines herbal medicine licorice (Glycyrrhiza uralensis). Although the pharmacological properties of GAs have long been known, attention to them has greatly increased in recent times due to their cytotoxic activity.Areas covered: This review represents the patents granted about natural and synthetic glycyrrhetinic acid analogs from January 2010 to December 2017, the advances made by research groups in conjunction with pharmaceutical companies in the discovery of new natural or synthetic glycyrrhetinic acid analogs.Expert opinion: GAs demonstrate excellent cytotoxic, antimicrobial, enzyme inhibitory, antiinflammatory, antioxidant, analgesic, and antiviral effects. It is interesting to note that the C-3(OH) and C30-CO2H functional groups make GAs very attractive lead structures for medicinal scientists since these functionalities allow the generation of further chemical diversity for improved pharmacological effects. Moreover, various GA analogues have been prepared via modification of the C30-CO2H. It is noteworthy that the C-30 amide of GA demonstrated better cytotoxic effects compared to the parent compounds. In addition, GAs have the capability to conjugate with other anticancer drugs or be converted into their halo or amino analogs which is expected to stimulate medicinal chemist to synthesize new lead compounds in cancer drug discovery.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 791
TI  - Journey Describing the Cytotoxic Potential of Withanolides: A Patent Review
JO  - Recent Pat. Anti-Canc. Drug Discov.
PY  - 2018
SP  - 411-421
AU  - Hussain, H.
AU  - Csuk, R.
AU  - Green, I. R.
AU  - Ur Rehman, N.
AU  - Abbas, G.
AU  - Hussain, W.
AU  - 
VL  - 13
UR  - 
DO  - 10.2174/1574892813666180808154928
AB  - Withanolides are C-28 ergostane steroids known to demonstrate some very interesting therapeutic properties. Numerous withanolides have been isolated from a variety of different plant species and can be employed to treat various types of cancers. Withanolides are indeed capable of demonstrating excellent anticancer, anti-inflammatory, and neuroprotective activities. Additionally, libraries of prepared withaferin A analogs incorporating an acyl, sulphate, amide and aldehyde functionality have demonstrated the most potential response. It is of particular interest to note that an acetyl group at either C-4, C-19 or C-27 enhances the anticancer effects. Since the majority of natural withanolides reported in patents are classified as “Type-A”, it is our opinion that there should now be a focus on developing “Type-B” withanolides and an investigation into their various therapeutic applications. Moreover, very little real innovation in synthetic methodologies has been reported which opens up huge possibilities for novel synthetic methodologies to be developed for the production of larger libraries new withanolides and their analogs to incorporate chemical diversity. In addition, since withanolides have the capability to conjugate with other anticancer compounds, this should encourage scientists to prepare lead compounds in cancer drug discovery.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 787
TI  - Droplet-Assisted Microfluidic Fabrication and Characterization of Multifunctional Polysaccharide Microgels Formed by Multicomponent Reactions
JO  - Polymers
PY  - 2018
SP  - 1055
AU  - Hauck, N.
AU  - Seixas, N.
AU  - Centeno, S. P.
AU  - Schlüßler, R.
AU  - Cojoc, G.
AU  - Müller, P.
AU  - Guck, J.
AU  - Wöll, D.
AU  - Wessjohann, L. A.
AU  - Thiele, J.
AU  - 
VL  - 10
UR  - 
DO  - 10.3390/polym10101055
AB  - Polysaccharide-based microgels have broad applications in multi-parametric cell cultures, cell-free biotechnology, and drug delivery. Multicomponent reactions like the Passerini three-component and the Ugi four-component reaction are shown in here to be versatile platforms for fabricating these polysaccharide microgels by droplet microfluidics with a narrow size distribution. While conventional microgel formation requires pre-modification of hydrogel building blocks to introduce certain functionality, in multicomponent reactions one building block can be simply exchanged by another to introduce and extend functionality in a library-like fashion. Beyond synthesizing a range of polysaccharide-based microgels utilizing hyaluronic acid, alginate and chitosan, exemplary in-depth analysis of hyaluronic acid-based Ugi four-component gels is conducted by colloidal probe atomic force microscopy, confocal Brillouin microscopy, quantitative phase imaging, and fluorescence correlation spectroscopy to elucidate the capability of microfluidic multicomponent reactions for forming defined polysaccharide microgel networks. Particularly, the impact of crosslinker amount and length is studied. A higher network density leads to higher Young’s moduli accompanied by smaller pore sizes with lower diffusion coefficients of tracer molecules in the highly homogeneous network, and vice versa. Moreover, tailored building blocks allow for crosslinking the microgels and incorporating functional groups at the same time as demonstrated for biotin-functionalized, chitosan-based microgels formed by Ugi four-component reaction. To these microgels, streptavidin-labeled enzymes are easily conjugated as shown for horseradish peroxidase (HRP), which retains its activity inside the microgels.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 783
TI  - The effect of simulated microgravity on the Brassica napus seedling proteome
JO  - Funct. Plant Biol.
PY  - 2018
SP  - 440-452
AU  - Frolov, A.
AU  - Didio, A.
AU  - Ihling, C.
AU  - Chantzeva, V.
AU  - Grishina, T.
AU  - Hoehenwarter, W.
AU  - Sinz, A.
AU  - Smolikova, G.
AU  - Bilova, T.
AU  - Medvedev, S.
AU  - 
VL  - 45
UR  - 
DO  - 10.1071/FP16378
AB  - The magnitude and the direction of the gravitational field represent an important environmental factor affecting plant development. In this context, the absence or frequent alterations of the gravity field (i.e. microgravity conditions) might compromise extraterrestrial agriculture and hence space inhabitation by humans. To overcome the deleterious effects of microgravity, a complete understanding of the underlying changes on the macromolecular level is necessary. However, although microgravity-related changes in gene expression are well characterised on the transcriptome level, proteomic data are limited. Moreover, information about the microgravity-induced changes in the seedling proteome during seed germination and the first steps of seedling development is completely missing. One of the valuable tools to assess gravity-related issues is 3D clinorotation (i.e. rotation in two axes). Therefore, here we address the effects of microgravity, simulated by a two-axial clinostat, on the proteome of 24- and 48-h-old seedlings of oilseed rape (Brassica napus L.). The liquid chromatography-MS-based proteomic analysis and database search revealed 95 up- and 38 downregulated proteins in the tryptic digests obtained from the seedlings subjected to simulated microgravity, with 42 and 52 annotations detected as being unique for 24- and 48-h treatment times, respectively. The polypeptides involved in protein metabolism, transport and signalling were annotated as the functional groups most strongly affected by 3-D clinorotation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 782
TI  - Mining seed proteome: from protein dynamics to modification profiles
JO  - Biol. Commun.
PY  - 2018
SP  - 43-58
AU  - Frolov, A.
AU  - Mamontova, T.
AU  - Ihling, C.
AU  - Lukasheva, E.
AU  - Bankin, M.
AU  - Chantseva, V.
AU  - Vikhnina, M.
AU  - Soboleva, A.
AU  - Shumilina, J.
AU  - Mavropolo-Stolyarenko, G.
AU  - Grishina, T.
AU  - Osmolovskaya, N.
AU  - Zhukov, V.
AU  - Hoehenwarter, W.
AU  - Sinz, A.
AU  - Tikhononovich, I.
AU  - Wessjohann, L.
AU  - Bilova, T.
AU  - Smolikova, G.
AU  - Medvedev, S.
AU  - 
VL  - 63
UR  - 
DO  - 10.21638/spbu03.2018.106
AB  - In the modern world, crop plants represent a major source of daily consumed foods. Among them, cereals and legumes — i.e. the crops accumulating oils, carbohydrates and proteins in their seeds — dominate in European agriculture, tremendously impacting global protein consumption and biodiesel production. Therefore, the seeds of crop plants attract the special attention of biologists, biochemists, nutritional physiologists and food chemists. Seed development and germination, as well as age- and stress-related changes in their viability and nutritional properties, can be addressed by a variety of physiological and biochemical methods. In this context, the methods of functional genomics can be applied to address characteristic changes in seed metabolism, which can give access to stress-resistant genotypes. Among these methods, proteomics is one of the most effective tools, allowing mining metabolism changes on the protein level. Here we discuss the main methodological approaches of seed proteomics in the context of physiological changes related to environmental stress and ageing. We provide a comprehensive comparison of gel- and chromatographybased approaches with a special emphasis on advantages and disadvantages of both strategies in characterization of the seed proteome.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 781
TI  - Derivatization of Methylglyoxal for LC-ESI-MS Analysis—Stability and Relative Sensitivity of Different Derivatives
JO  - Molecules
PY  - 2018
SP  - 2994
AU  - Fritzsche, S.
AU  - Billig, S.
AU  - Rynek, R.
AU  - Abburi, R.
AU  - Tarakhovskaya, E.
AU  - Leuner, O.
AU  - Frolov, A.
AU  - Birkemeyer, C.
AU  - 
VL  - 23
UR  - 
DO  - 10.3390/molecules23112994
AB  - The great research interest in the quantification of reactive carbonyl compounds (RCCs), such as methylglyoxal (MGO) in biological and environmental samples, is reflected by the fact that several publications have described specific strategies to perform this task. Thus, many reagents have also been reported for the derivatization of RCCs to effectively detect and quantify the resulting compounds using sensitive techniques such as liquid chromatography coupled with mass spectrometry (LC-MS). However, the choice of the derivatization protocol is not always clear, and a comparative evaluation is not feasible because detection limits from separate reports and determined with different instruments are hardly comparable. Consequently, for a systematic comparison, we tested 21 agents in one experimental setup for derivatization of RCCs prior to LC-MS analysis. This consisted of seven commonly employed reagents and 14 similar reagents, three of which were designed and synthesized by us. All reagents were probed for analytical responsiveness of the derivatives and stability of the reaction mixtures. The results showed that derivatives of 4-methoxyphenylenediamine and 3-methoxyphenylhydrazine—reported here for the first time for derivatization of RCCs—provided a particularly high responsiveness with ESI-MS detection. We applied the protocol to investigate MGO contamination of laboratory water and show successful quantification in a lipoxidation experiment. In summary, our results provide valuable information for scientists in establishing accurate analysis of RCCs.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 778
TI  - The major glucosinolate hydrolysis product in rocket (Eruca sativa L.), sativin, is 1,3-thiazepane-2-thione: Elucidation of structure, bioactivity, and stability compared to other rocket isothiocyanates
JO  - Food Chem.
PY  - 2018
SP  - 57-65
AU  - Fechner, J.
AU  - Kaufmann, M.
AU  - Herz, C.
AU  - Eisenschmidt, D.
AU  - Lamy, E.
AU  - Kroh, L. W.
AU  - Hanschen, F. S.
AU  - 
VL  - 261
UR  - 
DO  - 10.1016/j.foodchem.2018.04.023
AB  - Rocket is rich in glucosinolates and valued for its hot and spicy taste. Here we report the structure elucidation, bioactivity, and stability of the mainly formed glucosinolate hydrolysis product, namely sativin, which was formerly thought to be 4-mercaptobutyl isothiocyanate. However, by NMR characterization we revealed that sativin is in fact 1,3-thiazepane-2-thione, a tautomer of 4-mercaptobutyl isothiocyanate with 7-membered ring structure and so far unknown. This finding was further substantiated by conformation sampling using molecular modeling and total enthalpy calculation with density functional theory. During aqueous heat treatment sativin in general was quite stable, while the isothiocyanates erucin and sulforaphane were labile, having half-lives of 132 min and 56 min (pH 5, 100 °C), respectively. Moreover, using a WST-1 assay, we found that sativin did not reduce cell viability of HepG2 cells in a range of 0.3–30 µM, and, therefore, exhibited no cytotoxic effects in this cell line.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 776
TI  - Salicylic acid and its derivatives elicit the production of diterpenes and sterols in corals and their algal symbionts: a metabolomics approach to elicitor SAR
JO  - Metabolomics
PY  - 2018
SP  - 127
AU  - Farag, M. A.
AU  - Maamoun, A. A.
AU  - Meyer, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 14
UR  - 
DO  - 10.1007/s11306-018-1416-y
AB  - IntroductionThe production of marine drugs in its normal habitats is often low and depends greatly on ecological conditions. Chemical synthesis of marine drugs is not economically feasible owing to their complex structures. Biotechnology application via elicitation represents a promising tool to enhance metabolites yield that has yet to be explored in soft corals.ObjectivesStudy the elicitation impact of salicylic acid (SA) and six analogues in addition to a systemic acquired resistance inducer on secondary metabolites accumulation in the soft coral Sarcophyton ehrenbergi along with the symbiont zooxanthellae and if SA elicitation effect is extended to other coral species S. glaucum and Lobophyton pauciliforum.MethodsPost elicitation in the three corals and zooxanthella, metabolites were extracted and analyzed via UHPLC-MS coupled with chemometric tools.ResultsMultivariate data analysis of the UHPLC-MS data set revealed clear segregation of SA, amino-SA, and acetyl-SA elicited samples. An increased level ca. 6- and 8-fold of the diterpenes viz., sarcophytonolide I, sarcophine and a C28-sterol, was observed in SA and amino-SA groups, respectively. Post elicitation, the level of diepoxy-cembratriene increased 1.5-fold and 2.4-fold in 1 mM SA, and acetyl-SA (aspirin) treatment groups, respectively. S. glaucum and Lobophyton pauciliforum showed a 2-fold increase of diepoxy-cembratriene levels.ConclusionThese results suggest that SA could function as a general and somewhat selective diterpene inducing signaling molecule in soft corals. Structural consideration reveals initial structure–activity relationship (SAR) in SA derivatives that seem important for efficient diterpene and sterol elicitation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 775
TI  - Gas Chromatography/Mass Spectrometry-Based Metabolite Profiling of Nutrients and Antinutrients in Eight Lens and Lupinus Seeds (Fabaceae)
JO  - J. Agr. Food Chem.
PY  - 2018
SP  - 4267-4280
AU  - Farag, M. A.
AU  - Khattab, A. R.
AU  - Ehrlich, A.
AU  - Kropf, M.
AU  - Heiss, A. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 66
UR  - 
DO  - 10.1021/acs.jafc.8b00369
AB  - Lens culinaris and several Lupinus species are two legumes regarded as potential protein resources aside from their richness in phytochemicals. Consequently, characterization of their metabolite composition seems warranted to be considered as a sustainable commercial functional food. This study presents a discriminatory holistic approach for metabolite profiling in accessions of four lentil cultivars and four Lupinus species via gas chromatography/mass spectrometry. A total of 107 metabolites were identified, encompassing organic and amino acids, sugars, and sterols, along with antinutrients, viz., alkaloids and sugar phosphates. Among the examined specimens, four nutritionally valuable accessions ought to be prioritized for future breeding to include Lupinus hispanicus, enriched in organic (ca. 11.7%) and amino acids (ca. 5%), and Lupinus angustifolius, rich in sucrose (ca. 40%), along with two dark-colored lentil cultivars ‘verte du Puy’ and ‘Black Beluga’ enriched in peptides. Antinutrient chemicals were observed in Lupinus polyphyllus, owing to its high alkaloid content. Several species-specific markers were also revealed using multivariate data analyses.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 774
TI  - Comparative Metabolomics Approach Detects Stress-Specific Responses during Coral Bleaching in Soft Corals
JO  - J. Proteome Res.
PY  - 2018
SP  - 2060-2071
AU  - Farag, M. A.
AU  - Meyer, A.
AU  - Ali, S. E.
AU  - Salem, M. A.
AU  - Giavalisco, P.
AU  - Westphal, H.
AU  - Wessjohann, L. A.
AU  - 
VL  - 17
UR  - 
DO  - 10.1021/acs.jproteome.7b00929
AB  - Chronic exposure to ocean acidification and elevated sea-surface temperatures pose significant stress to marine ecosystems. This in turn necessitates costly acclimation responses in corals in both the symbiont and host, with a reorganization of cell metabolism and structure. A large-scale untargeted metabolomics approach comprising gas chromatography mass spectrometry (GC–MS) and ultraperformance liquid chromatography coupled to high resolution mass spectrometry (UPLC–MS) was applied to profile the metabolite composition of the soft coral Sarcophyton ehrenbergi and its dinoflagellate symbiont. Metabolite profiling compared ambient conditions with response to simulated climate change stressors and with the sister species, S. glaucum. Among ∼300 monitored metabolites, 13 metabolites were modulated. Incubation experiments providing four selected upregulated metabolites (alanine, GABA, nicotinic acid, and proline) in the culturing water failed to subside the bleaching response at temperature-induced stress, despite their known ability to mitigate heat stress in plants or animals. Thus, the results hint to metabolite accumulation (marker) during heat stress. This study provides the first detailed map of metabolic pathways transition in corals in response to different environmental stresses, accounting for the superior thermal tolerance of S. ehrenbergi versus S. glaucum, which can ultimately help maintain a viable symbiosis and mitigate against coral bleaching.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 773
TI  - NMR approach for the authentication of 10 cinnamon spice accessions analyzed via chemometric tools
JO  - LWT
PY  - 2018
SP  - 491-498
AU  - Farag, M. A.
AU  - Labib, R. M.
AU  - Noleto, C.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 90
UR  - 
DO  - 10.1016/j.lwt.2017.12.069
AB  - Quantitative NMR metabolomics approach was developed to distinguish two cinnamon species (Ceylon Cinnamon, Cinnamomum verum and Chinese Cinnamon, Cinnamomum cassia) that are interchangeably used in food products. The results of the analyses of 10 bark accessions revealed for 9 key sensory metabolites, with (E)-cinnamaldehyde as the major form. Multivariate data analyses revealed for eugenol leading presence in C. verum versus fatty acid enrichment in C. cassia. This research provides the first NMR metabolites fingerprinting of the two major cinnamon resources. Compounds related to C. verum aroma and taste were identified and quantified that can be utilized as markers for the authentication of this valuable drug. Novel insight on metabolites mediating for C. verum antidiabetic effect is also presented.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 772
TI  - Delivery of [Ru(η6-p-cymene)Cl2{Ph2P(CH2)3SPh-κP}] using unfunctionalized and mercapto functionalized SBA-15 mesoporous silica: Preparation, characterization and in vitro study
JO  - J. Inorg. Biochem.
PY  - 2018
SP  - 155-162
AU  - Edeler, D.
AU  - Arlt, S.
AU  - Petković, V.
AU  - Ludwig, G.
AU  - Drača, D.
AU  - Maksimović-Ivanić, D.
AU  - Mijatović, S.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 180
UR  - 
DO  - 10.1016/j.jinorgbio.2017.12.011
AB  - SBA-15 (Santa Barbara Amorphous 15) mesoporous silica and its functionalized form (with 3-mercaptopropyltriethoxysilane) SBA-15~SH were used as carriers for [Ru(η6-p-cymene)Cl2{Ph2P(CH2)3SPh-κP}] complex, denoted as [Ru]. Prepared mesoporous silica nanomaterials were characterized by traditional methods. Materials without [Ru] complex did not show any cytotoxic activity against melanoma B16 and B16-F10 cell lines. On the contrary, materials containing [Ru] such as SBA-15&#124;[Ru] and SBA-15~SH&#124;[Ru], exhibited very high activity against tested tumor cell lines, moreover with similar inhibitory potential. According to the loaded amount of the [Ru] in SBA-15&#124;[Ru] and SBA-15~SH&#124;[Ru] the IC50 values are 1–2μM depending on the test used, thus in comparison to [Ru] alone the activity of nanomaterials containing [Ru] are elevated 3–6 times in vitro. However, the mechanism of apoptosis induction differs for these two mesoporous silica. Unlike reference [Ru] compound and SBA-15~SH&#124;[Ru], SBA-15&#124;[Ru] induces high caspase activation. Discrepancy in mechanism of drugs action at intracellular level points towards an influence of functionalization as well as availability of the drug. Moreover, both SBA-15&#124;[Ru] and SBA-15~SH&#124;[Ru] similarly to [Ru] are declining autophagy in B16 cell line.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 767
TI  - An efficient cyclization of lapachol to new benzo[h]chromene hybrid compounds: a stepwise vs. one-pot esterification-click (CuAAC) study
JO  - New J. Chem.
PY  - 2018
SP  - 19591-19599
AU  - de la Torre, A. F.
AU  - Ali, A.
AU  - Westermann, B.
AU  - Schmeda-Hirschmann, G.
AU  - Walter Pertino, M.
AU  - 
VL  - 42
UR  - 
DO  - 10.1039/C8NJ03699C
AB  - A straightforward one-pot vs. stepwise esterification of lapachol was performed to obtain highly diversified heterocycles. Whereas the one-pot esterification leads to mono esterified lapachol, the stepwise approach generated benzo[h]chromene. Furthermore, benzo[h]chromene architectures with embedded triazole moieties were synthesized through late-stage functionalization of the benzo[h]chromene terminal alkyne moiety by copper catalyzed 1,3-dipolar cycloaddition (CuAAC) in a one-pot procedure.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 765
TI  - Apoptosis caused by triterpenes and phytosterols and antioxidant activity of an enriched flavonoid extract and from Passiflora mucronata
JO  - Anti-Cancer Agents Med. Chem.
PY  - 2018
SP  - 1405-1416
AU  - da Silva, I. C. V.
AU  - Kaluderovic, G.
AU  - de Oliveira, P. F.
AU  - Guimaraes, D. O.
AU  - Quaresma, C. H.
AU  - Porzel, A.
AU  - Muzitano, M. F.
AU  - Wessjohann, L. A.
AU  - Leal, I. C. R.
AU  - 
VL  - 18
UR  - 
DO  - 10.2174/1871520618666180315090949
AB  - Background: P. mucronata (Pm) comes from South America, Brazil and is characterized as “Maracujá de Restinga”. It is used in folk medicine for its soothing properties and in treating insomnia. Objective: The present study for the first time analyzed the antioxidant and cytotoxicity of the hydroalcoholic leaves extract and fractions from Pm. Method: The cytotoxicity test will be evaluated by different assays (MTT and CV) against human prostate cancer (PC3) and mouse malignant melanoma (B16F10) cell lines, and the antioxidant test by DPPH method. Results: β-Amyrin, oleanolic acid, β-sitosterol and stigmasterol were isolated of the most active, hexane fraction. These substances were tested against the tumor cell lines: β-sitosterol and stigmasterol showed the most relevant activity to PC3 in CV assay and, oleanolic acid to B16F10 by the MTT assay. In addition, it was possible to indicate that the mode of cell death for stigmasterol, presumably is apoptosis. In terms of antioxidant activity, the hydroalcoholic leaves extract presented higher activity (EC50 133.3 μg/mL) compared to the flower (EC50 152.3 μg/mL) and fruit (EC50 207.9 μg/mL) extracts. By the HPLC-MS, it was possible to identify the presence of flavones in the leaf extract (isoschaftoside, schaftoside, isovitexin, vitexin, isoorientin, orientin). Conclusions: P. mucronata hexane fraction showed promising cytotoxic effect against cancer cell lines, and stigmasterol contributes to this activity, inducing apoptosis of these cells. Furthermore, as other Passiflora species, Pm extract showed antioxidant activity and flavones are its major phenolic compounds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 764
TI  - An OPR3-independent pathway uses 4,5-didehydrojasmonate for jasmonate synthesis
JO  - Nat. Chem. Biol.
PY  - 2018
SP  - 171-178
AU  - Chini, A.
AU  - Monte, I.
AU  - Zamarreño, A. M.
AU  - Hamberg, M.
AU  - Lassueur, S.
AU  - Reymond, P.
AU  - Weiss, S.
AU  - Stintzi, A.
AU  - Schaller, A.
AU  - Porzel, A.
AU  - García-Mina, J. M.
AU  - Solano, R.
AU  - 
VL  - 14
UR  - 
DO  - 10.1038/nchembio.2540
AB  - Biosynthesis of the phytohormone jasmonoyl-isoleucine (JA-Ile) requires reduction of the JA precursor 12-oxo-phytodienoic acid (OPDA) by OPDA reductase 3 (OPR3). Previous analyses of the opr3-1 Arabidopsis mutant suggested an OPDA signaling role independent of JA-Ile and its receptor COI1; however, this hypothesis has been challenged because opr3-1 is a conditional allele not completely impaired in JA-Ile biosynthesis. To clarify the role of OPR3 and OPDA in JA-independent defenses, we isolated and characterized a loss-of-function opr3-3 allele. Strikingly, opr3-3 plants remained resistant to necrotrophic pathogens and insect feeding, and activated COI1-dependent JA-mediated gene expression. Analysis of OPDA derivatives identified 4,5-didehydro-JA in wounded wild-type and opr3-3 plants. OPR2 was found to reduce 4,5-didehydro-JA to JA, explaining the accumulation of JA-Ile and activation of JA-Ile-responses in opr3-3 mutants. Our results demonstrate that in the absence of OPR3, OPDA enters the β-oxidation pathway to produce 4,5-ddh-JA as a direct precursor of JA and JA-Ile, thus identifying an OPR3-independent pathway for JA biosynthesis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 762
TI  - Intrinsic Xenobiotic Resistance of the Intestinal Stem Cell Niche
JO  - Dev. Cell
PY  - 2018
SP  - 681-695.e5
AU  - Chee, Y. C.
AU  - Pahnke, J.
AU  - Bunte, R.
AU  - Adsool, V. A.
AU  - Madan, B.
AU  - Virshup, D. M.
AU  - 
VL  - 46
UR  - 
DO  - 10.1016/j.devcel.2018.07.023
AB  - The gut absorbs dietary nutrients and provides a barrier to xenobiotics and microbiome metabolites. To cope with toxin exposures, the intestinal epithelium is one of the most rapidly proliferating tissues in the body. The stem cell niche supplies essential signaling factors including Wnt proteins secreted by subepithelial myofibroblasts. Unexpectedly, therapeutically effective doses of orally administered PORCN inhibitors that block all Wnt secretion do not affect intestinal homeostasis. We find that intestinal myofibroblasts are intrinsically resistant to multiple xenobiotics, including PORCN inhibitors and the anthracycline antibiotic doxorubicin. These myofibroblasts have high expression of a subset of drug transporters; knockout of Mrp1/Abcc1 enhances drug sensitivity. Tamoxifen administration to Rosa26CreERT2;mT/mG mice visually highlights the drug-resistant intestinal stromal compartment and identifies small populations of drug-resistant cells in lung, kidney, and pancreatic islets. Xenobiotic resistance of the Wnt-producing myofibroblasts can protect the intestinal stem cell niche in the face of an unpredictable environment.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 761
TI  - Changes in isovitexin-O-glycosylation during the development of young barley plants
JO  - Phytochemistry
PY  - 2018
SP  - 11-20
AU  - Brauch, D.
AU  - Porzel, A.
AU  - Schumann, E.
AU  - Pillen, K.
AU  - Mock, H.-P.
AU  - 
VL  - 148
UR  - 
DO  - 10.1016/j.phytochem.2018.01.001
AB  - Phenylpropanoids are a class of plant natural products that have many biological functions, including stress defence. In barley, phenylpropanoids have been described as having protective properties against excess UV-B radiation and have been linked to resistance to pathogens. Although the phenylpropanoid composition of barley has recently been addressed in more detail, the biosynthesis and regulation of this pathway have not been fully established. Barley introgression lines, such as the S42IL-population offer a set of genetically diverse plants that enable the correlation of metabolic data to distinct genetic regions on the barley genome and, subsequently, identification of relevant genes.The phenylpropanoid profiles of the first and third leaf of barley seedlings in Scarlett and four members of the S42IL-population were obtained by LC-MS. Comparison of the leaf profiles revealed a change in the glycosylation pattern of the flavone-6-C-glucoside isovitexin in the elite cultivar Scarlett. The change was characterized by the stepwise decrease in isovitexin-7-O-glucoside (saponarin) and an increase in isovitexin-2″-O-β-D-glucoside content.The lines S42IL-101-, -177 and -178 were completely devoid of isovitexin-2″-O-β-D-glucoside. Parallel glucosyltransferase assays were consistent with the observed metabolic patterns. The genetic region responsible for this metabolic effect was located on chromosome 1H between 0.21 and 15.08 cM, encompassing 505 gene candidates in the genome of the sequenced cultivar Morex. Only one of these genes displayed sequence similarity with glucosyltransferases of plant secondary metabolism that possessed the characteristic PSPG motif.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 759
TI  - Corrigendum to “Morphometric analysis of the cerebral expression of ATP-binding cassette transporter protein ABCB1 in chronic schizophrenia: Circumscribed deficits in the habenula” [Schizophr. Res. 2016 Nov;177(1–3):52–58]
JO  - Schizophr. Res.
PY  - 2018
SP  - 622-623
AU  - Bernstein, H.
AU  - Hildebrandt, J.
AU  - Dobrowolny, H.
AU  - Steiner, J.
AU  - Bogerts, B.
AU  - Pahnke, J.
AU  - 
VL  - 197
UR  - 
DO  - 10.1016/j.schres.2018.03.036
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 756
TI  - Iron is a centrally bound cofactor of specifier proteins involved in glucosinolate breakdown
JO  - PLOS ONE
PY  - 2018
SP  - e0205755
AU  - Backenköhler, A.
AU  - Eisenschmidt, D.
AU  - Schneegans, N.
AU  - Strieker, M.
AU  - Brandt, W.
AU  - Wittstock, U.
AU  - 
VL  - 13
UR  - 
DO  - 10.1371/journal.pone.0205755
AB  - Glucosinolates, a group of sulfur-rich thioglucosides found in plants of the order Brassicales, have attracted a lot of interest as chemical defenses of plants and health promoting substances in human diet. They are accumulated separately from their hydrolyzing enzymes, myrosinases, within the intact plant, but undergo myrosinase-catalyzed hydrolysis upon tissue disruption. This results in various biologically active products, e.g. isothiocyanates, simple nitriles, epithionitriles, and organic thiocyanates. While formation of isothiocyanates proceeds by a spontaneous rearrangement of the glucosinolate aglucone, aglucone conversion to the other products involves specifier proteins under physiological conditions. Specifier proteins appear to act with high specificity, but their exact roles and the structural bases of their specificity are presently unknown. Previous research identified the motif EXXXDXXXH as potential iron binding site required for activity, but crystal structures of recombinant specifier proteins lacked the iron cofactor. Here, we provide experimental evidence for the presence of iron (most likely Fe2+) in purified recombinant thiocyanate-forming protein from Thlaspi arvense (TaTFP) using a Ferene S-based photometric assay as well as Inductively Coupled Plasma-Mass Spectrometry. Iron binding and activity depend on E266, D270, and H274 suggesting a direct interaction of Fe2+ with these residues. Furthermore, we demonstrate presence of iron in epithiospecifier protein and nitrile-specifier protein 3 from Arabidopsis thaliana (AtESP and AtNSP3). We also present a homology model of AtNSP3. In agreement with this model, iron binding and activity of AtNSP3 depend on E386, D390, and H394. The homology model further suggests that the active site of AtNSP3 imposes fewer restrictions to the glucosinolate aglucone conformation than that of TaTFP and AtESP due to its larger size. This may explain why AtNSP3 does not support epithionitrile or thiocyanate formation, which likely requires exact positioning of the aglucone thiolate relative to the side chain.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 848
TI  - A subset of chemosensory genes differs between two populations of a specialized leaf beetle after host plant shift
JO  - Ecol. Evol.
PY  - 2018
SP  - 8055-8075
AU  - Wang, D.
AU  - Pentzold, S.
AU  - Kunert, M.
AU  - Groth, M.
AU  - Brandt, W.
AU  - Pasteels, J. M.
AU  - Boland, W.
AU  - Burse, A.
AU  - 
VL  - 8
UR  - 
DO  - 10.1002/ece3.4246
AB  - Due to its fundamental role in shaping host selection behavior, we have analyzed the chemosensory repertoire of Chrysomela lapponica. This specialized leaf beetle evolved distinct populations which shifted from the ancestral host plant, willow (Salix sp., Salicaceae), to birch (Betula rotundifolia, Betulaceae). We identified 114 chemosensory candidate genes in adult C. lapponica: 41 olfactory receptors (ORs), eight gustatory receptors, 17 ionotropic receptors, four sensory neuron membrane proteins, 32 odorant binding proteins (OBPs), and 12 chemosensory proteins (CSP) by RNA‐seq. Differential expression analyses in the antennae revealed significant upregulation of one minus‐C OBP (ClapOBP27) and one CSP (ClapCSP12) in the willow feeders. In contrast, one OR (ClapOR17), four minus‐C OBPs (ClapOBP02, 07, 13, 20), and one plus‐C OBP (ClapOBP32) were significantly upregulated in birch feeders. The differential expression pattern in the legs was more complex. To narrow down putative ligands acting as cues for host discrimination, the relative abundance and diversity of volatiles of the two host plant species were analyzed. In addition to salicylaldehyde (willow‐specific), both plant species differed mainly in their emission rate of terpenoids such as (E,E)‐α‐farnesene (high in willow) or 4,8‐dimethylnona‐1,3,7‐triene (high in birch). Qualitatively, the volatiles were similar between willow and birch leaves constituting an “olfactory bridge” for the beetles. Subsequent structural modeling of the three most differentially expressed OBPs and docking studies using 22 host volatiles indicated that ligands bind with varying affinity. We suggest that the evolution of particularly minus‐C OBPs and ORs in C. lapponica facilitated its host plant shift via chemosensation of the phytochemicals from birch as novel host plant.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 847
TI  - Traceable platinum(II) complexes with alkylene diamine-derived ligands: synthesis, characterization and in vitro studies
JO  - J. Coord. Chem.
PY  - 2018
SP  - 243-257
AU  - Walther, T.
AU  - Herzog, R.
AU  - Kaluđerović, M. R.
AU  - Wagner, C.
AU  - Schmidt, H.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 71
UR  - 
DO  - 10.1080/00958972.2018.1431392
AB  - Diiodido- (6a/6b) and dichloridoplatinum(II) complexes (7a/7b) with fluorescent ligands 2-[(2-aminoethyl)amino]ethyl-2-(methylamino)benzoate (5a) and 2-amino-1-(aminoethyl)ethyl-2-(methylamino)benzoate (5b) were prepared and characterized by elemental analysis, ESI-MS analysis, fluorescence spectrometry, as well as 1H, 13C, and 195Pt NMR spectroscopy. All compounds have been tested against A2780 ovarian cancer, A549 lung carcinoma, and HT-29 colon cancer cell lines using sulforhodamine-B assay. The activity increased from ligand precursors, diiodido- to dichloridoplatinum(II) complexes, except against HT-29 cell line where diiodido and dichlorido expressed similar activity. These compounds enter the tumor cells and emit a bright fluorescence at ca. 470 nm, mainly targeting nuclei.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 843
TI  - Enhanced structural diversity in terpenoid biosynthesis: enzymes, substrates and cofactors
JO  - Org. Biomol. Chem.
PY  - 2018
SP  - 348-362
AU  - Vattekkatte, A.
AU  - Garms, S.
AU  - Brandt, W.
AU  - Boland, W.
AU  - 
VL  - 16
UR  - 
DO  - 10.1039/C7OB02040F
AB  - The enormous diversity of terpenes found in nature is generated by enzymes known as terpene synthases, or cyclases. Some are also known for their ability to convert a single substrate into multiple products. This review comprises monoterpene and sesquiterpene synthases that are multiproduct in nature along with the regulation factors that can alter the product specificity of multiproduct terpene synthases without genetic mutations. Variations in specific assay conditions with focus on shifts in product specificity based on change in metal cofactors, assay pH and substrate geometry are described. Alterations in these simple cellular conditions provide the organism with enhanced chemodiversity without investing into new enzymatic architecture. This versatility to modulate product diversity grants organisms, especially immobile ones like plants with access to an enhanced defensive repertoire by simply altering cofactors, pH level and substrate geometry.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 837
TI  - Development and validation of LC/APCI-MS method for the quantification of oat ceramides in skin permeation studies
JO  - Anal. Bioanal. Chem.
PY  - 2018
SP  - 4775-4785
AU  - Tessema, E. N.
AU  - Gebre-Mariam, T.
AU  - Frolov, A.
AU  - Wohlrab, J.
AU  - Neubert, R. H. H.
AU  - 
VL  - 410
UR  - 
DO  - 10.1007/s00216-018-1162-z
AB  - Ceramides (CERs) are the backbone of the intercellular lipid lamellae of the stratum corneum (SC), the outer layer of the skin. Skin diseases such as atopic dermatitis, psoriasis, and aged skin are characterized by dysfunctional skin barrier and dryness which are associated with reduced levels of CERs. Replenishing the depleted epidermal CERs with exogenous CERs has been shown to have beneficial effects in improving the skin barrier and hydration. The exogenous CERs such as phyto-derived CERs (PhytoCERs) can be delivered deep into the SC using novel topical formulations. This, however, requires investigating the rate and extent of skin permeation of CERs. In this study, an LC/APCI-MS method to detect and quantify PhytoCERs in different layers of the skin has been developed and validated. The method was used to investigate the skin permeation of PhytoCERs using Franz diffusion cells after applying an amphiphilic cream containing PhytoCERs to the surface of ex vivo human skin. As plant-specific CERs are not commercially available, well-characterized CERs isolated from oat (Avena abyssinica) were used as reference standards for the development and validation of the method. The method was linear over the range of 30–1050 ng/mL and sensitive with limit of detection and quantification of 10 and 30 ng/mL, respectively. The method was also selective, accurate, and precise with minimal matrix effect (with mean matrix factor around 100%). Even if more than 85% of oat CERs in the cream remained in the cream after the incubation periods of 30, 100, and 300 min, it was possible to quantify the small quantities of oat CERs distributed across the SC, epidermis, and dermis of the skin indicating the method’s sensitivity. Therefore, the method can be used to investigate the skin permeation of oat CERs from the various pharmaceutical and cosmeceutical products without any interference from the skin constituents such as the epidermal lipids.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 835
TI  - Identification of UDP glucosyltransferases from the aluminum-resistant tree Eucalyptus camaldulensis forming β-glucogallin, the precursor of hydrolyzable tannins
JO  - Phytochemistry
PY  - 2018
SP  - 154-161
AU  - Tahara, K.
AU  - Nishiguchi, M.
AU  - Frolov, A.
AU  - Mittasch, J.
AU  - Milkowski, C.
AU  - 
VL  - 152
UR  - 
DO  - 10.1016/j.phytochem.2018.05.005
AB  - In the highly aluminum-resistant tree Eucalyptus camaldulensis, hydrolyzable tannins are proposed to play a role in internal detoxification of aluminum, which is a major factor inhibiting plant growth on acid soils. To understand and modulate the molecular mechanisms of aluminum detoxification by hydrolyzable tannins, the biosynthetic genes need to be identified. In this study, we identified and characterized genes encoding UDP-glucose:gallate glucosyltransferase, which catalyzes the formation of 1-O-galloyl-β-d-glucose (β-glucogallin), the precursor of hydrolyzable tannins. By homology-based cloning, seven full-length candidate cDNAs were isolated from E. camaldulensis and expressed in Escherichia coli as recombinant N-terminal His-tagged proteins. Phylogenetic analysis classified four of these as UDP glycosyltransferase (UGT) 84A subfamily proteins (UGT84A25a, -b, UGT84A26a, -b) and the other three as UGT84J subfamily proteins (UGT84J3, -4, -5). In vitro enzyme assays showed that the UGT84A proteins catalyzed esterification of UDP–glucose and gallic acid to form 1-O-galloyl-β-d-glucose, whereas the UGT84J proteins were inactive. Further analyses with UGT84A25a and −26a indicated that they also formed 1-O-glucose esters of other structurally related hydroxybenzoic and hydroxycinnamic acids with a preference for hydroxybenzoic acids. The UGT84A genes were expressed in leaves, stems, and roots of E. camaldulensis, regardless of aluminum stress. Taken together, our results suggest that the UGT84A subfamily enzymes of E. camaldulensis are responsible for constitutive production of 1-O-galloyl-β-d-glucose, which is the first step of hydrolyzable tannin biosynthesis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 834
TI  - The concerted amyloid-beta clearance of LRP1 and ABCB1/P-gp across the blood-brain barrier is linked by PICALM
JO  - Brain Behav. Immun.
PY  - 2018
SP  - 21-33
AU  - Storck, S. E.
AU  - Hartz, A. M.
AU  - Bernard, J.
AU  - Wolf, A.
AU  - Kachlmeier, A.
AU  - Mahringer, A.
AU  - Weggen, S.
AU  - Pahnke, J.
AU  - Pietrzik, C. U.
AU  - 
VL  - 73
UR  - 
DO  - 10.1016/j.bbi.2018.07.017
AB  - The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic hallmark of Alzheimer’s disease (AD). The blood-brain barrier (BBB) provides a large surface area and has been shown to be an important mediator for removal of brain Aβ. Both, the ABC transporter P-glycoprotein (ABCB1/P-gp) and the receptor low-density lipoprotein receptor-related protein 1 (LRP1) have been implicated to play crucial roles in Aβ efflux from brain. Here, with immunoprecipitation experiments, co-immunostainings and dual inhibition of ABCB1/P-gp and LRP1, we show that both proteins are functionally linked, mediating a concerted transcytosis of Aβ through endothelial cells. Late-onset AD risk factor Phosphatidylinositol binding clathrin assembly protein (PICALM) is associated with both ABCB1/P-gp and LRP1 representing a functional link and guiding both proteins through the brain endothelium. Together, our results give more mechanistic insight on Aβ transport across the BBB and show that the functional interplay of different clearance proteins is needed for the rapid removal of Aβ from the brain.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 826
TI  - nmrML: A Community Supported Open Data Standard for the Description, Storage, and Exchange of NMR Data
JO  - Anal. Chem.
PY  - 2018
SP  - 649-656
AU  - Schober, D.
AU  - Jacob, D.
AU  - Wilson, M.
AU  - Cruz, J. A.
AU  - Marcu, A.
AU  - Grant, J. R.
AU  - Moing, A.
AU  - Deborde, C.
AU  - de Figueiredo, L. F.
AU  - Haug, K.
AU  - Rocca-Serra, P.
AU  - Easton, J.
AU  - Ebbels, T. M. D.
AU  - Hao, J.
AU  - Ludwig, C.
AU  - Günther, U. L.
AU  - Rosato, A.
AU  - Klein, M. S.
AU  - Lewis, I. A.
AU  - Luchinat, C.
AU  - Jones, A. R.
AU  - Grauslys, A.
AU  - Larralde, M.
AU  - Yokochi, M.
AU  - Kobayashi, N.
AU  - Porzel, A.
AU  - Griffin, J. L.
AU  - Viant, M. R.
AU  - Wishart, D. S.
AU  - Steinbeck, C.
AU  - Salek, R. M.
AU  - Neumann, S.
AU  - 
VL  - 90
UR  - 
DO  - 10.1021/acs.analchem.7b02795
AB  - NMR is a widely used analytical technique with a growing number of repositories available. As a result, demands for a vendor-agnostic, open data format for long-term archiving of NMR data have emerged with the aim to ease and encourage sharing, comparison, and reuse of NMR data. Here we present nmrML, an open XML-based exchange and storage format for NMR spectral data. The nmrML format is intended to be fully compatible with existing NMR data for chemical, biochemical, and metabolomics experiments. nmrML can capture raw NMR data, spectral data acquisition parameters, and where available spectral metadata, such as chemical structures associated with spectral assignments. The nmrML format is compatible with pure-compound NMR data for reference spectral libraries as well as NMR data from complex biomixtures, i.e., metabolomics experiments. To facilitate format conversions, we provide nmrML converters for Bruker, JEOL and Agilent/Varian vendor formats. In addition, easy-to-use Web-based spectral viewing, processing, and spectral assignment tools that read and write nmrML have been developed. Software libraries and Web services for data validation are available for tool developers and end-users. The nmrML format has already been adopted for capturing and disseminating NMR data for small molecules by several open source data processing tools and metabolomics reference spectral libraries, e.g., serving as storage format for the MetaboLights data repository. The nmrML open access data standard has been endorsed by the Metabolomics Standards Initiative (MSI), and we here encourage user participation and feedback to increase usability and make it a successful standard.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 825
TI  - Malusides, novel glucosylceramides isolated from apple pomace (Malus domestica)
JO  - Z. Naturforsch. C
PY  - 2018
SP  - 33-39
AU  - Reisberg, M.
AU  - Arnold, N.
AU  - Porzel, A.
AU  - Neubert, R. H.
AU  - Dräger, B.
AU  - 
VL  - 73
UR  - 
DO  - 10.1515/znc-2017-0059
AB  - Three new glucosylceramides (GluCers) named malusides I–III (1–3) were isolated from apple (cultivars of Malus domestica) pomace (fruit material remaining after juice extraction). An unusual oxo/hydroxy group pattern within the sphingadienine (d18:2) type sphingoid base was observed. All compounds contained the same α-hydroxylated fatty acid (h16:0) and a β-D-glucose moiety. Their structures were assigned on the basis of one- and two-dimensional (1D and 2D) nuclear magnetic resonance (NMR) spectroscopic analyses and mass spectrometry (MS) measurements.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 824
TI  - Diversity Driven Decoration and Ligation of Fullerene by Ugi and Passerini Multicomponent Reactions
JO  - Chem.-Eur. J.
PY  - 2018
SP  - 9788-9793
AU  - Ravanello, B. B.
AU  - Seixas, N.
AU  - Rodrigues, O. E. D.
AU  - da Silva, R. S.
AU  - Villetti, M. A.
AU  - Frolov, A.
AU  - Rivera, D. G.
AU  - Westermann, B.
AU  - 
VL  - 24
UR  - 
DO  - 10.1002/chem.201802414
AB  - Aiming at providing an efficient and versatile method for the diversity‐oriented decoration and ligation of fullerenes, we report the first C60 derivatization strategy based on isocyanide‐multicomponent reactions (I‐MCRs). The approach comprises the use of Passerini and Ugi reactions for assembling pseudo‐peptidic scaffolds (i.e., N‐alkylated and depsipeptides, peptoids) on carboxylic acid‐functionalized fullerenes. The method showed wide substrate scope for the oxo and isocyanide components, albeit the Ugi reaction proved efficient only for aromatic amines. The approach was successfully employed for the ligation of oligopeptides and polyethyleneglycol chains (PEG) to C60, as well as for the construction of bis‐antennary as well as PEG‐tethered dimeric fullerenes. The quantum yields for the formation of 1O2 was remarkable for the selected compounds analyzed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 823
TI  - Comparative analysis of Hibiscus sabdariffa (roselle) hot and cold extracts in respect to their potential for α-glucosidase inhibition
JO  - Food Chem.
PY  - 2018
SP  - 236-244
AU  - Rasheed, D. M.
AU  - Porzel, A.
AU  - Frolov, A.
AU  - El Seedi, H. R.
AU  - Wessjohann, L. A.
AU  - Farag, M. A.
AU  - 
VL  - 250
UR  - 
DO  - 10.1016/j.foodchem.2018.01.020
AB  - Roselle (Hibiscus sabdariffa) is a functional food with potential health benefits, consumed either as hot or cold beverage. To ensure quality control of its various products, accurate measurement of active metabolites is warranted. Herein, we propose a combination of ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) and nuclear magnetic resonance (NMR) analytical platforms for the untargeted characterization of metabolites in two roselle cultivars, Aswan and Sudan-1. The analyses revealed 33 metabolites, including sugars, flavonoids, anthocyanins, phenolic and aliphatic organic acids. Their relative contents in cultivars were assessed via principle component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS). Impact of the different extraction methods (decoction, infusion and maceration) was compared by quantitative 1H NMR spectroscopy, revealing cold maceration to be optimal for preserving anthocyanins, whereas infusion was more suited for recovering organic acids. The metabolite pattern revealed by the different extraction methods was found in good correlation for their ability to inhibit α-glucosidase enzyme.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 817
TI  - Methodology of Drought Stress Research: Experimental Setup and Physiological Characterization
JO  - Int. J. Mol. Sci.
PY  - 2018
SP  - 4089
AU  - Osmolovskaya, N.
AU  - Shumilina, J.
AU  - Kim, A.
AU  - Didio, A.
AU  - Grishina, T.
AU  - Bilova, T.
AU  - Keltsieva, O. A.
AU  - Zhukov, V.
AU  - Tikhonovich, I.
AU  - Tarakhovskaya, E.
AU  - Frolov, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 19
UR  - 
DO  - 10.3390/ijms19124089
AB  - Drought is one of the major stress factors affecting the growth and development of plants. In this context, drought-related losses of crop plant productivity impede sustainable agriculture all over the world. In general, plants respond to water deficits by multiple physiological and metabolic adaptations at the molecular, cellular, and organism levels. To understand the underlying mechanisms of drought tolerance, adequate stress models and arrays of reliable stress markers are required. Therefore, in this review we comprehensively address currently available models of drought stress, based on culturing plants in soil, hydroponically, or in agar culture, and critically discuss advantages and limitations of each design. We also address the methodology of drought stress characterization and discuss it in the context of real experimental approaches. Further, we highlight the trends of methodological developments in drought stress research, i.e., complementing conventional tests with quantification of phytohormones and reactive oxygen species (ROS), measuring antioxidant enzyme activities, and comprehensively profiling transcriptome, proteome, and metabolome.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 814
TI  - Real-time detection of N-end rule-mediated ubiquitination via fluorescently labeled substrate probes
JO  - New Phytol.
PY  - 2018
SP  - 613-624
AU  - Mot, A. C.
AU  - Prell, E.
AU  - Klecker, M.
AU  - Naumann, C.
AU  - Faden, F.
AU  - Westermann, B.
AU  - Dissmeyer, N.
AU  - 
VL  - 217
UR  - 
DO  - 10.1111/nph.14497
AB  - The N‐end rule pathway has emerged as a major system for regulating protein functions by controlling their turnover in medical, animal and plant sciences as well as agriculture. Although novel functions and enzymes of the pathway have been discovered, the ubiquitination mechanism and substrate specificity of N‐end rule pathway E3 ubiquitin ligases have remained elusive. Taking the first discovered bona fide plant N‐end rule E3 ligase PROTEOLYSIS1 (PRT1) as a model, we used a novel tool to molecularly characterize polyubiquitination live, in real time.We gained mechanistic insights into PRT1 substrate preference and activation by monitoring live ubiquitination using a fluorescent chemical probe coupled to artificial substrate reporters. Ubiquitination was measured by rapid in‐gel fluorescence scanning as well as in real time by fluorescence polarization.The enzymatic activity, substrate specificity, mechanisms and reaction optimization of PRT1‐mediated ubiquitination were investigated ad hoc instantaneously and with significantly reduced reagent consumption.We demonstrated that PRT1 is indeed an E3 ligase, which has been hypothesized for over two decades. These results demonstrate that PRT1 has the potential to be involved in polyubiquitination of various substrates and therefore pave the way to understanding recently discovered phenotypes of prt1 mutants.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 813
TI  - IR and NMR spectroscopic correlation of enterobactin by DFT
JO  - Spectrochim. Acta A
PY  - 2018
SP  - 264-277
AU  - Moreno, M.
AU  - Zacarias, A.
AU  - Porzel, A.
AU  - Velasquez, L.
AU  - Gonzalez, G.
AU  - Alegría-Arcos, M.
AU  - Gonzalez-Nilo, F.
AU  - Gross, E. K. U.
AU  - 
VL  - 198
UR  - 
DO  - 10.1016/j.saa.2018.02.060
AB  - Emerging and re-emerging epidemic diseases pose an ongoing threat to global health. Currently, Enterobactin and Enterobactin derivatives have gained interest, owing to their potential application in the pharmaceutical field. As it is known [J. Am. Chem. Soc (1979) 101, 20, 6097–6104], Enterobactin (H6EB) is an efficient iron carrier synthesized and secreted by many microbial species. In order to facilitate the elucidation of enterobactin and its analogues, here we propose the creation of a H6EB standard set using Density Functional Theory Infrared (IR) and NMR spectra. We used two exchange-correlation (xc) functionals (PBE including long-range corrections LC-PBE and mPW1), 2 basis sets (QZVP and 6-31G(d)) and 2 grids (fine and ultrafine) for most of the H6EB structures dependent of dihedral angles. The results show a significant difference between the OH and NH bands, while the CO amide and O(CO) IR bands are often found on top of each other. The NMR DFT calculations show a strong dependence on the xc functional, basis set, and grid used for the H6EB structure. Calculated 1H and 13C NMR spectra enable the effect of the solvent to be understood in the context of the experimental measurements. The good agreement between the experimental and the calculated spectra using LC-PBE/QZVP and ultrafine grid suggest the possibility of the systems reported here to be considered as a standard set. The dependence of electrostatic potential and frontier orbitals with the catecholamide dihedral angles of H6EB is described. The matrix-assisted laser desorption/ionization time of the flight mass spectrometry (MALDI-TOF MS) of H6EB is also reported of manner to enrich the knowledge about its reactivity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 811
TI  - Naturally occurring compounds in differentiation based therapy of cancer
JO  - Biotechnol. Adv.
PY  - 2018
SP  - 1622-1632
AU  - Mijatović, S.
AU  - Bramanti, A.
AU  - Nicoletti, F.
AU  - Fagone, P.
AU  - Kaluđerović, G. N.
AU  - Maksimović-Ivanić, D.
AU  - 
VL  - 36
UR  - 
DO  - 10.1016/j.biotechadv.2018.04.001
AB  - Differentiation of cancer cells entails the reversion of phenotype from malignant to the original. The conversion to cell type characteristic for another tissue is named transdifferentiation. Differentiation/transdifferentiation of malignant cells in high grade tumor mass could serve as a nonaggressive approach that potentially limits tumor progression and augments chemosensitivity. While this therapeutic strategy is already being used for treatment of hematological cancers, its feasibility for solid malignancies is still debated. We will presently discuss the natural compounds that show these properties, with focus on anthraquinones from Aloe vera, Senna, Rheum sp. and hop derived prenylflavonoids.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 810
TI  - Memory enhancement by ferulic acid ester across species
JO  - Sci. Adv.
PY  - 2018
SP  - eaat6994
AU  - Michels, B.
AU  - Zwaka, H.
AU  - Bartels, R.
AU  - Lushchak, O.
AU  - Franke, K.
AU  - Endres, T.
AU  - Fendt, M.
AU  - Song, I.
AU  - Bakr, M.
AU  - Budragchaa, T.
AU  - Westermann, B.
AU  - Mishra, D.
AU  - Eschbach, C.
AU  - Schreyer, S.
AU  - Lingnau, A.
AU  - Vahl, C.
AU  - Hilker, M.
AU  - Menzel, R.
AU  - Kähne, T.
AU  - Leßmann, V.
AU  - Dityatev, A.
AU  - Wessjohann, L.
AU  - Gerber, B.
AU  - 
VL  - 4
UR  - 
DO  - 10.1126/sciadv.aat6994
AB  - Cognitive impairments can be devastating for quality of life, and thus, preventing or counteracting them is of great value. To this end, the present study exploits the potential of the plant Rhodiola rosea and identifies the constituent ferulic acid eicosyl ester [icosyl-(2E)-3-(4-hydroxy-3-methoxyphenyl)-prop-2-enoate (FAE-20)] as a memory enhancer. We show that food supplementation with dried root material from R. rosea dose-dependently improves odor-taste reward associative memory scores in larval Drosophila and prevents the age-related decline of this appetitive memory in adult flies. Task-relevant sensorimotor faculties remain unaltered. From a parallel approach, a list of candidate compounds has been derived, including R. rosea–derived FAE-20. Here, we show that both R. rosea–derived FAE-20 and synthetic FAE-20 are effective as memory enhancers in larval Drosophila. Synthetic FAE-20 also partially compensates for age-related memory decline in adult flies, as well as genetically induced early-onset loss of memory function in young flies. Furthermore, it increases excitability in mouse hippocampal CA1 neurons, leads to more stable context-shock aversive associative memory in young adult (3-month-old) mice, and increases memory scores in old (&gt;2-year-old) mice. Given these effects, and given the utility of R. rosea—the plant from which we discovered FAE-20—as a memory enhancer, these results may hold potential for clinical applications.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 809
TI  - Multicomponent polysaccharide–protein bioconjugation in the development of antibacterial glycoconjugate vaccine candidates
JO  - Chem. Sci.
PY  - 2018
SP  - 2581-2588
AU  - Méndez, Y.
AU  - Chang, J.
AU  - Humpierre, A. R.
AU  - Zanuy, A.
AU  - Garrido, R.
AU  - Vasco, A. V.
AU  - Pedroso, J.
AU  - Santana, D.
AU  - Rodríguez, L. M.
AU  - García-Rivera, D.
AU  - Valdés, Y.
AU  - Vérez-Bencomo, V.
AU  - Rivera, D. G.
AU  - 
VL  - 9
UR  - 
DO  - 10.1039/C7SC05467J
AB  - A new synthetic strategy for the development of multivalent antibacterial glycoconjugate vaccines is described. The approach comprises the utilization of an isocyanide-based multicomponent process for the conjugation of functionalized capsular polysaccharides of S. pneumoniae and S. Typhi to carrier proteins such as diphtheria and tetanus toxoids. For the first time, oxo- and carboxylic acid-functionalized polysaccharides could be either independently or simultaneously conjugated to immunogenic proteins by means of the Ugi-multicomponent reaction, thus leading to mono- or multivalent unimolecular glycoconjugates as vaccine candidates. Despite the high molecular weight of the two or three reacting biomolecules, the multicomponent bioconjugation proved highly efficient and reproducible. The Ugi-derived glycoconjugates showed notable antigenicity and elicited good titers of functional specific antibodies. To our knowledge, this is the only bioconjugation method that enables the incorporation of two different polysaccharidic antigens to a carrier protein in a single step. Applications in the field of self-adjuvanting, eventually anticancer, multicomponent vaccines are foreseeable.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 807
TI  - Protein Carbonylation and Glycation in Legume Nodules
JO  - Plant Physiol.
PY  - 2018
SP  - 1510-1528
AU  - Matamoros, M. A.
AU  - Kim, A.
AU  - Peñuelas, M.
AU  - Ihling, C.
AU  - Griesser, E.
AU  - Hoffmann, R.
AU  - Fedorova, M.
AU  - Frolov, A.
AU  - Becana, M.
AU  - 
VL  - 177
UR  - 
DO  - 10.1104/pp.18.00533
AB  - Nitrogen fixation is an agronomically and environmentally important process catalyzed by bacterial nitrogenase within legume root nodules. These unique symbiotic organs have high metabolic rates and produce large amounts of reactive oxygen species that may modify proteins irreversibly. Here, we examined two types of oxidative posttranslational modifications of nodule proteins: carbonylation, which occurs by direct oxidation of certain amino acids or by interaction with reactive aldehydes arising from cell membrane lipid peroxides; and glycation, which results from the reaction of Lys and Arg residues with reducing sugars or their auto-oxidation products. We used a strategy based on the enrichment of carbonylated peptides by affinity chromatography followed by liquid chromatography-tandem mass spectrometry to identify 369 oxidized proteins in bean (Phaseolus vulgaris) nodules. Of these, 238 corresponded to plant proteins and 131 to bacterial proteins. Lipid peroxidation products induced most carbonylation sites. This study also revealed that carbonylation has major effects on two key nodule proteins. Metal-catalyzed oxidation caused inactivation of malate dehydrogenase and aggregation of leghemoglobin. In addition, numerous glycated proteins were identified in vivo, including three key nodule proteins: sucrose synthase, glutamine synthetase, and glutamate synthase. Label-free quantification identified 10 plant proteins and 18 bacterial proteins as age-specifically glycated. Overall, our results suggest that the selective carbonylation or glycation of crucial proteins involved in nitrogen metabolism, transcriptional regulation, and signaling may constitute a mechanism to control cell metabolism and nodule senescence.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 806
TI  - Proteome Map of Pea (Pisum sativum L.) Embryos Containing Different Amounts of Residual Chlorophylls
JO  - Int. J. Mol. Sci.
PY  - 2018
SP  - 4066
AU  - Mamontova, T.
AU  - Lukasheva, E.
AU  - Mavropolo-Stolyarenko, G.
AU  - Proksch, C.
AU  - Bilova, T.
AU  - Kim, A.
AU  - Babakov, V.
AU  - Grishina, T.
AU  - Hoehenwarter, W.
AU  - Medvedev, S.
AU  - Smolikova, G.
AU  - Frolov, A.
AU  - 
VL  - 19
UR  - 
DO  - 10.3390/ijms19124066
AB  - Due to low culturing costs and high seed protein contents, legumes represent the main global source of food protein. Pea (Pisum sativum L.) is one of the major legume crops, impacting both animal feed and human nutrition. Therefore, the quality of pea seeds needs to be ensured in the context of sustainable crop production and nutritional efficiency. Apparently, changes in seed protein patterns might directly affect both of these aspects. Thus, here, we address the pea seed proteome in detail and provide, to the best of our knowledge, the most comprehensive annotation of the functions and intracellular localization of pea seed proteins. To address possible intercultivar differences, we compared seed proteomes of yellow- and green-seeded pea cultivars in a comprehensive case study. The analysis revealed totally 1938 and 1989 nonredundant proteins, respectively. Only 35 and 44 proteins, respectively, could be additionally identified after protamine sulfate precipitation (PSP), potentially indicating the high efficiency of our experimental workflow. Totally 981 protein groups were assigned to 34 functional classes, which were to a large extent differentially represented in yellow and green seeds. Closer analysis of these differences by processing of the data in KEGG and String databases revealed their possible relation to a higher metabolic status and reduced longevity of green seeds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 805
TI  - Influence of breast cancer resistance protein and P-glycoprotein on tissue distribution and excretion of Ko143 assessed with PET imaging in mice
JO  - Eur. J. Pharm. Sci.
PY  - 2018
SP  - 212-222
AU  - Mairinger, S.
AU  - Zoufal, V.
AU  - Wanek, T.
AU  - Traxl, A.
AU  - Filip, T.
AU  - Sauberer, M.
AU  - Stanek, J.
AU  - Kuntner, C.
AU  - Pahnke, J.
AU  - Müller, M.
AU  - Langer, O.
AU  - 
VL  - 115
UR  - 
DO  - 10.1016/j.ejps.2018.01.034
AB  - Ko143 is a reference inhibitor of the adenosine triphosphate-binding cassette (ABC) transporter breast cancer resistance protein (humans: ABCG2, rodents: Abcg2) for in vitro and in vivo use. Previous in vitro data indicate that Ko143 binds specifically to ABCG2/Abcg2, suggesting a potential utility of Ko143 as a positron emission tomography (PET) tracer to assess the density (abundance) of ABCG2 in different tissues. In this work we radiolabeled Ko143 with carbon-11 (11C) and performed small-animal PET experiments with [11C]Ko143 in wild-type, Abcg2(−/−), Abcb1a/b(−/−) and Abcb1a/b(−/−)Abcg2(−/−) mice to assess the influence of Abcg2 and Abcb1a/b on tissue distribution and excretion of [11C]Ko143.[11C]Ko143 was extensively metabolized in vivo and unidentified radiolabeled metabolites were found in all investigated tissues. We detected no significant differences between wild-type and Abcg2(−/−) mice in the distribution of [11C]Ko143-derived radioactivity to Abcg2-expressing organs (brain, liver and kidney). [11C]Ko143 and possibly its radiolabeled metabolites were transported by Abcb1a and not by Abcg2 at the mouse blood-brain barrier. [11C]Ko143-derived radioactivity underwent both hepatobiliary and urinary excretion, with Abcg2 playing a possible role in mediating the transport of radiolabeled metabolites of [11C]Ko143 from the kidney into urine. Experiments in which a pharmacologic dose of unlabeled Ko143 (10 mg/kg) was co-administered with [11C]Ko143 revealed pronounced effects of the vehicle used for Ko143 formulation (containing polyethylene glycol 300 and polysorbate 80) on radioactivity distribution to the brain and the liver, as well as on hepatobiliary and urinary excretion of radioactivity.Our results highlight the challenges associated with the development of PET tracers for ABC transporters and emphasize that inhibitory effects of pharmaceutical excipients on membrane transporters need to be considered when performing in vivo drug-drug interaction studies. Finally, our study illustrates the power of small-animal PET to assess the interaction of drug molecules with membrane transporters on a whole body level.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 804
TI  - Rosellin A and B, two red diketopiperazine alkaloids from the mushroom Mycena rosella
JO  - Tetrahedron
PY  - 2018
SP  - 5113-5118
AU  - Lohmann, J. S.
AU  - von Nussbaum, M.
AU  - Brandt, W.
AU  - Mülbradt, J.
AU  - Steglich, W.
AU  - Spiteller, P.
AU  - 
VL  - 74
UR  - 
DO  - 10.1016/j.tet.2018.06.049
AB  - Rosellin A and B, two red diketopiperazine alkaloids with unprecedented structures, have been isolated from the fruiting bodies of the mushroom Mycena rosella. The structures of the rosellins were mainly deduced from their 2D NMR and HRMS (ESI) spectra. Their absolute configuration was determined by comparison of the CD spectra of the rosellins with the corresponding CD spectra obtained by quantum chemical calculations. Root exposure to rosellin A led to bleaching of the leaves of Lepidium sativum plants.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 803
TI  - Loss of epithelium-specific GPx2 results in aberrant cell fate decisions during intestinal differentiation
JO  - Oncotarget
PY  - 2018
SP  - 539-552
AU  - Lennicke, C.
AU  - Rahn, J.
AU  - Wickenhauser, C.
AU  - Lichtenfels, R.
AU  - Müller, A. S.
AU  - Wessjohann, L. A.
AU  - Kipp, A. P.
AU  - Seliger, B.
AU  - 
VL  - 9
UR  - 
DO  - 10.18632/oncotarget.22640
AB  - The selenoprotein glutathione peroxidase 2 (GPx2) is expressed in the epithelium of the gastrointestinal tract, where it is thought to be involved in maintaining mucosal homeostasis. To gain novel insights into the role of GPx2, proteomic profiles of colonic tissues either derived from wild type (WT) or GPx2 knockout (KO) mice, maintained under selenium (Se) deficiency or adequate Se supplementation conditions were established and analyzed. Amongst the panel of differentially expressed proteins, the calcium-activated chloride channel regulator 1 (CLCA1) was significantly down-regulated in GPx2 KO versus WT mice regardless of the given Se status. Moreover, transcript levels of the isoforms CLCA2 and CLCA3 showed a similar expression pattern. In the intestine, CLCA1 is usually restricted to mucin-producing goblet cells. However, although -SeKO mice had the highest numbers of goblet cells as confirmed by significantly enhanced mRNA expression levels of the goblet cell marker mucin-2, the observed expression pattern suggests that GPx2 KO goblet cells might be limited in synthesizing CLCA1. Furthermore, transcript levels of differentiation markers such as chromogranin-1 (Chga) for enteroendocrine cells and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) for stem cells were also downregulated in GPx2 KO mice. Moreover, this was accompanied by a downregulation of the mRNA expression levels of the intestinal hormones glucagon-like peptide 1 (Glp1), ghrelin (Ghrl) and somatostatin (Sst). Thus, it seems that GPx2 might be important for the modulation of cell fate decisions in the murine intestinal epithelium.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 802
TI  - Survival Associations Using Perfusion and Diffusion Magnetic Resonance Imaging in Patients With Histologic and Genetic Defined Diffuse Glioma World Health Organization Grades II and III
JO  - J. Comput. Assist. Tomo.
PY  - 2018
SP  - 807-815
AU  - Latysheva, A.
AU  - Eeg Emblem, K.
AU  - Server, A.
AU  - Brandal, P.
AU  - Meling, T. R.
AU  - Pahnke, J.
AU  - Hald, J. K.
AU  - 
VL  - 42
UR  - 
DO  - 10.1097/RCT.0000000000000742
AB  - Objective According to the new World Health Organization 2016 classification for tumors of the central nervous system, 1p/19q codeletion defines the genetic hallmark that differentiates oligodendrogliomas from diffuse astrocytomas. The aim of our study was to evaluate whether relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) histogram analysis can stratify survival in adult patients with genetic defined diffuse glioma grades II and III.Methods Sixty-seven patients with untreated diffuse gliomas World Health Organization grades II and III and known 1p/19q codeletion status were included retrospectively and analyzed using ADC and rCBV maps based on whole-tumor volume histograms. Overall survival and progression-free survival (PFS) were analyzed by using Kaplan-Meier and Cox survival analyses adjusted for known survival predictors.Results Significant longer PFS was associated with homogeneous rCBV distribution–higher rCBVpeak (median, 37 vs 26 months; hazard ratio [HR], 3.2; P = 0.02) in patients with astrocytomas, and heterogeneous rCBV distribution–lower rCBVpeak (median, 46 vs 37 months; HR, 5.3; P &lt; 0.001) and higher rCBVmean (median, 44 vs 39 months; HR, 7.9; P = 0.003) in patients with oligodendrogliomas. Apparent diffusion coefficient parameters (ADCpeak, ADCmean) did not stratify PFS and overall survival.Conclusions Tumors with heterogeneous perfusion signatures and high average values were associated with longer PFS in patients with oligodendrogliomas. On the contrary, heterogeneous perfusion distribution was associated with poor outcome in patients with diffuse astrocytomas.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 801
TI  - ABCA7 Downregulation Modifies Cellular Cholesterol Homeostasis and Decreases Amyloid-β Peptide Efflux in an in vitro Model of the Blood-Brain Barrier
JO  - J. Alzheimers Dis.
PY  - 2018
SP  - 1195-1211
AU  - Lamartinière, Y.
AU  - Boucau, M.-C.
AU  - Dehouck, L.
AU  - Krohn, M.
AU  - Pahnke, J.
AU  - Candela, P.
AU  - Gosselet, F.
AU  - Fenart, L.
AU  - 
VL  - 64
UR  - 
DO  - 10.3233/JAD-170883
AB  - The role of ABCA7 in brain homeostasis and Alzheimer’s disease (AD) is currently under intense scrutiny, since it has been reported that polymorphisms in the Abca7 gene and a loss of function of the protein are closely linked to excessive accumulation of amyloid peptides and disturbed cholesterol homeostasis. The blood-brain barrier (BBB), which isolates the brain from the blood compartment, is involved in both of these processes. We therefore hypothesized that ABCA7 downregulation might affect cholesterol and amyloid exchanges at the BBB. Using siRNA and primary cultures of mouse endothelial cells purified from brain microvessels and seeded on Transwell ® inserts, we investigated the role of ABCA7 in cholesterol and amyloid exchanges across the BBB. Our results showed that a decrease in ABCA7 expression at the BBB provokes in vitro a reduction in ABCA1 expression and a decrease in APOE secretion. In vitro, these decreases reduce cholesterol exchange across the BBB, particularly for high-density lipoproteins and ApoA-I particles. When ABCA7 was absent, we observed a reduction in Aβ peptide basolateral-to-apical transport in the presence of ApoA-I, with non-significant changes in the expression levels of Rage, Lrp1, Abcb1, Abcc1, and Abcg2. Our study in murine BBB model highlighted a putative new role for ABCA7 in AD via the protein’s involvement in cholesterol metabolism and amyloid clearance at the BBB.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 800
TI  - Humanization of the blood–brain barrier transporter ABCB1 in mice disrupts genomic locus — lessons from three unsuccessful approaches
JO  - Eur. J. Microbiol. Immunol.
PY  - 2018
SP  - 78-86
AU  - Krohn, M.
AU  - Wanek, T.
AU  - Menet, M.-C.
AU  - Noack, A.
AU  - Declèves, X.
AU  - Langer, O.
AU  - Löscher, W.
AU  - Pahnke, J.
AU  - 
VL  - 8
UR  - 
DO  - 10.1556/1886.2018.00008
AB  - ATP-binding cassette (ABC) transporters are of major importance for the restricted access of toxins and drugs to the human body. At the body&#39;s barrier tissues like the blood–brain barrier, these transporters are highly represented. Especially, ABCB1 (P-glycoprotein) has been a priority target of pharmaceutical research, for instance, to aid chemotherapy of cancers, therapy resistant epilepsy, and lately even neurodegenerative diseases. To improve translational research, the humanization of mouse genes has become a popular tool although, like recently seen for Abcb1, not all approaches were successful. Here, we report the characterization of another unsuccessful commercially available ABCB1 humanized mouse strain. In vivo assessment of transporter activity using positron emission tomography imaging revealed a severe reduction of ABCB1 function in the brain of these mice. Analyses of brain mRNA and protein expression showed that the murine Abcb1a gene is still expressed in homozygous humanized animals while expression of the human gene is minimal. Promoter region analyses underpinned that the introduced human gene might dysregulate normal expression and provided insights into the regulation of both transcription and translation of Abcb1a. We conclude that insertion of the human coding DNA sequence (CDS) into exon 3 instead of exon 2 most probably represents a more promising strategy for Abcb1a humanization.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 831
TI  - Photochemical activity changes accompanying the embryogenesis of pea (Pisum sativum) with yellow and green cotyledons
JO  - Funct. Plant Biol.
PY  - 2018
SP  - 228-235
AU  - Smolikova, G.
AU  - Kreslavski, V.
AU  - Shiroglazova, O.
AU  - Bilova, T.
AU  - Sharova, E.
AU  - Frolov, A.
AU  - Medvedev, S.
AU  - 
VL  - 45
UR  - 
DO  - 10.1071/FP16379
AB  - The pea seeds are photosynthetically active until the end of the maturation phase, when the embryonic chlorophylls degrade. However, in some cultivars, the underlying mechanisms are compromised, and the mature seeds preserve green colour. The residual chlorophylls can enhance oxidative degradation of reserve biomolecules, and affect thereby the quality, shelf life and nutritive value of seeds. Despite this, the formation, degradation, and physical properties of the seed chlorophylls are still not completely characterised. So here we address the dynamics of seed photochemical activity in the yellow- and green-seeded pea cultivars by the pulse amplitude modulation (PAM) fluorometric analysis. The experiments revealed the maximal photochemical activity at the early- and mid-cotyledon stages. Thereby, the active centres of PSII were saturated at the light intensity of 15–20 µmol photons m–2 s–1. Despite of their shielding from the light by the pod wall and seed coat, photochemical reactions can be registered in the seeds with green embryo. Importantly, even at the low light intensities, the photochemical activity in the coats and cotyledons could be detected. The fast transients of the chlorophyll a fluorescence revealed a higher photochemical activity in the coat of yellow-seeded cultivars in comparison to those with the green-seeded ones. However, it declined rapidly in all seeds at the late cotyledon stage, and was accompanied with the decrease of the seed water content. Thus, the termination of photosynthetic activity in seeds is triggered by their dehydration.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 828
TI  - ChemFrag: Chemically meaningful annotation of fragment ion mass spectra
JO  - J. Mass Spectrom.
PY  - 2018
SP  - 1104-1115
AU  - Schüler, J.-A.
AU  - Neumann, S.
AU  - Müller-Hannemann, M.
AU  - Brandt, W.
AU  - 
VL  - 53
UR  - 
DO  - 10.1002/jms.4278
AB  - Identification and structural determination of small molecules by mass spectrometry is an important step in chemistry and biochemistry. However, the chemically realistic annotation of a fragment ion spectrum can be a difficult challenge. We developed ChemFrag, for the detection of fragmentation pathways and the annotation of fragment ions with chemically reasonable structures. ChemFrag combines a quantum chemical with a rule‐based approach. For different doping substances as test instances, ChemFrag correctly annotates fragment ions. In most cases, the predicted fragments are chemically more realistic than those from purely combinatorial approaches, or approaches based on machine learning. The annotation generated by ChemFrag often coincides with spectra that have been manually annotated by experts. This is a major advance in peak annotation and allows a more precise automatic interpretation of mass spectra.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 961
TI  - In Vitro Anticancer Evaluation of Platinum(II/IV) Complexes with Diisoamyl Ester of (S,S)-ethylenediamine-N,N’-di-2-propanoic Acid
JO  - Anti-Cancer Agents Med. Chem.
PY  - 2017
SP  - 1136-1143
AU  - Zmejkovski, B. B.
AU  - Pantelić, N.
AU  - Filipović, L.
AU  - Aranđelović, S.
AU  - Radulović, S.
AU  - Sabo, T. J.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 17
UR  - 
DO  - 10.2174/1871520616666161207155634
AB  - Aims: Platinum(II) and platinum(IV) complexes [PtCln{(S,S)-(i-Am)2eddip}] (n = 2, 4: 1, 2, respectively; (S,S)-(i-Am)2eddip = O,O’-diisoamyl-(S,S)-ethylenediamine-N,N’-di-2-propanoate) were synthesized and characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy and mass spectrometry.Method: Quantum chemical calculations were used to predict formed isomers of 1 and 2. Furthermore, reduction of 2 with ascorbic acid was followed by time-dependant 13C NMR spectroscopy in order to enable assignation of the formed isomers for complex 1. In vitro cytotoxic activity was determined for 1 and 2 on a panel of five human tumor cell lines derived from cervix adenocarcinoma (HeLa), alveolar basal adenocarcinoma (A549), breast adenocarcinoma (MDA-453), colorectal cancer (LS 174), erythromyeloblastoid leukemia (K562), as well as one non-malignant human lung fibroblast cell line (MRC-5), using MTT assay. Result: Both complexes exhibited high (2 against K562: IC50 = 5.4 μM), more active than cisplatin, to moderate activity (1). Both complexes caused considerable decrease of cell number in K562 cells in G1, S and G2 phases, concordantly increasing subpopulation in sub-G1 fraction. Morphological analysis of K562 cell death induced by platinum(II/IV) complexes indicate apoptosis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 956
TI  - Piperlongumine B and analogs are promising and selective inhibitors for acetylcholinesterase
JO  - Eur. J. Med. Chem.
PY  - 2017
SP  - 222-231
AU  - Wiemann, J.
AU  - Karasch, J.
AU  - Loesche, A.
AU  - Heller, L.
AU  - Brandt, W.
AU  - Csuk, R.
AU  - 
VL  - 139
UR  - 
DO  - 10.1016/j.ejmech.2017.07.081
AB  - Piperlongumine B (19), an alkaloid previously isolated from long pepper (Piper longum) has been synthesized for the first time in a short sequence and in good yield together with 19 analogs. Screening of these compounds in Ellman&#39;s assays showed several of them to be good inhibitors of acetylcholinesterase while being less active for butyrylcholinesterase. Activity of the compounds increased with the ring size of the heterocycle, and a maximum of activity was observed for an analog holding 12 methylene groups in the aliphatic side chain. These compounds may be regarded as promising candidates for the development of efficient inhibitors of acetylcholinesterase being useful for the treatment of Alzheimer&#39;s disease.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 954
TI  - One-Pot Assembly of Amino Acid Bridged Hybrid Macromulticyclic Cages through Multiple Multicomponent Macrocyclizations
JO  - Angew. Chem.
PY  - 2017
SP  - 3555-3559
AU  - Wessjohann, L. A.
AU  - Kreye, O.
AU  - Rivera, D. G.
AU  - 
VL  - 129
UR  - 
DO  - 10.1002/ange.201610801
AB  - An important development in the field of macrocyclization strategies towards molecular cages is described. The approach comprises the utilization of a double Ugi four‐component macrocyclization for the assembly of macromulticycles with up to four different tethers, that is, hybrid cages. The innovation of this method rests on setting up the macromulticycle connectivities not through the tethers but through the bridgeheads, which in this case involve N‐substituted amino acids. Both dilution and metal‐template‐driven macrocyclization conditions were implemented with success, enabling the one‐pot formation of cryptands and cages including steroidal, polyether, heterocyclic, peptidic, and aryl tethers. This method demonstrates substantial complexity‐generating character and is suitable for applications in molecular recognition and catalysis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 953
TI  - One-Pot Assembly of Amino Acid Bridged Hybrid Macromulticyclic Cages through Multiple Multicomponent Macrocyclizations
JO  - Angew. Chem. Int. Ed.
PY  - 2017
SP  - 3501-3505
AU  - Wessjohann, L. A.
AU  - Kreye, O.
AU  - Rivera, D. G.
AU  - 
VL  - 56
UR  - 
DO  - 10.1002/anie.201610801
AB  - An important development in the field of macrocyclization strategies towards molecular cages is described. The approach comprises the utilization of a double Ugi four‐component macrocyclization for the assembly of macromulticycles with up to four different tethers, that is, hybrid cages. The innovation of this method rests on setting up the macromulticycle connectivities not through the tethers but through the bridgeheads, which in this case involve N‐substituted amino acids. Both dilution and metal‐template‐driven macrocyclization conditions were implemented with success, enabling the one‐pot formation of cryptands and cages including steroidal, polyether, heterocyclic, peptidic, and aryl tethers. This method demonstrates substantial complexity‐generating character and is suitable for applications in molecular recognition and catalysis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 930
TI  - No Silver Bullet – Canonical Poly(ADP-Ribose) Polymerases (PARPs) Are No Universal Factors of Abiotic and Biotic Stress Resistance of Arabidopsis thaliana
JO  - Front. Plant Sci.
PY  - 2017
SP  - 59
AU  - Rissel, D.
AU  - Heym, P. P.
AU  - Thor, K.
AU  - Brandt, W.
AU  - Wessjohann, L. A.
AU  - Peiter, E.
AU  - 
VL  - 8
UR  - 
DO  - 10.3389/fpls.2017.00059
AB  - Abiotic and biotic stress can have a detrimental impact on plant growth and productivity. Hence, there is a substantial demand for key factors of stress responses to improve yield stability of crops. Members of the poly(ADP-ribose)polymerase (PARP) protein family, which post-translationally modify (PARylate) nuclear proteins, have been suggested as such universal determinants of plant stress responses. A role under abiotic stress has been inferred from studies in which a genetic or, more commonly, pharmacological inhibition of PARP activity improved the performance of stressed plants. To further elucidate the role of PARP proteins under stress, T-DNA knockout mutants for the three Arabidopsis thaliana PARP genes were subjected to drought, osmotic, salt, and oxidative stress. To exclude a functional redundancy, which was indicated by a transcriptional upregulation of the remaining parp genes, a parp triple mutant was generated. Surprisingly, parp mutant plants did not differ from wild type plants in any of these stress experiments, independent from the number of PARP genes mutated. The parp triple mutant was also analyzed for callose formation in response to the pathogenassociated molecular pattern flg22. Unexpectedly, callose formation was unaltered in the mutant, albeit pharmacological PARP inhibition robustly blocked this immune response, confirming previous reports. Evidently, pharmacological inhibition appears to be more robust than the abolition of all PARP genes, indicating the presence of so-far undescribed proteins with PARP activity. This was supported by the finding that protein PARylation was not absent, but even increased in the parp triple mutant. Candidates for novel PARP-inhibitor targets may be found in the SRO protein family. These proteins harbor a catalytic PARP-like domain and are centrally involved in stress responses. Molecular modeling analyses, employing animal PARPs as templates, indeed indicated a capability of the SRO proteins RCD1 and SRO1 to bind nicotinamide-derived inhibitors. Collectively, the results of our study suggest that the stress-related phenotypes of parp mutants are highly conditional, and they call for a reconsideration of PARP inhibitor studies. In the context of this study, we also propose a unifying nomenclature of PARP genes and parp mutants, which is currently highly inconsistent and redundant.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 929
TI  - Quantification of glycosylceramides in plants by automated multiple development–high-performance thin-layer chromatography
JO  - JPC - J. Planar Chromat.
PY  - 2017
SP  - 460-466
AU  - Reisberg, M.
AU  - Arnold, N.
AU  - Bisrat, D.
AU  - Asres, K.
AU  - Neubert, R. H.
AU  - Dräger, B.
AU  - 
VL  - 30
UR  - 
DO  - 10.1556/1006.2017.30.6.1
AB  - Glycosylceramides (GlyCers) are precursors of ceramides (Cers) that are major components of the outer layer of human skin, the stratum corneum. A Cer deficiency is associated with skin diseases such as psoriasis and atopic dermatitis and can be treated with Cer-containing semisolid formulations. Plants may serve as alternative sources for expensive semisynthetic Cer production. Since the GlyCer contents of plants vary widely, there is a need to develop a rapid, simple, selective, and precise method for GlyCer quantification in plants. In the present study, an effective and validated automated multiple development‒high-performance thin-layer chromatography (AMD‒HPTLC) method has been developed for GlyCer quantification in 9 different plant materials. An 18-step gradient elution program (n-hexane, chloroform, ethyl acetate, methanol) led to a clear separation of bands from complex matrices and allowed densitometric analysis for quantification purposes. Apple pomace and wheat germs yielded 26.8 and 39.5 mg of GlyCer per 100 g plant material, respectively, while the yields of coffee grounds were below the limit of quantification. The GlyCer contents of the seeds of six Fabaceae species, namely, Albizia grandibracteata, Albizia gummifera, Albizia lebbeck, Albizia schimperiana, Acacia etbaica, and Robinia pseudoacacia, ranged from 9.4 to 23.1 mg per 100 g plant material. GlyCers were separated by preparative thin-layer chromatography (TLC) and identified by offline high-performance liquid chromatography–mass spectrometry (HPLC–MS). Intact GlyCers were detected in the Fabaceae species for the first time. A simple AMD–HPTLC screening and quantification technique for GlyCers was developed, which may serve as a tool in searching plant GlyCers for a possible “phyto”-Cer production.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 928
TI  - Production of Rare Phyto-Ceramides from Abundant Food Plant Residues
JO  - J. Agr. Food Chem.
PY  - 2017
SP  - 1507-1517
AU  - Reisberg, M.
AU  - Arnold, N.
AU  - Porzel, A.
AU  - Neubert, R. H. H.
AU  - Dräger, B.
AU  - 
VL  - 65
UR  - 
DO  - 10.1021/acs.jafc.6b04275
AB  - Ceramides (Cers) are major components of the outermost layer of the skin, the stratum corneum, and play a crucial role in permeability barrier functions. Alterations in Cer composition causing skin diseases are compensated with semisynthetic skin-identical Cers. Plants constitute new resources for Cer production as they contain glucosylceramides (GluCers) as major components. GluCers were purified from industrial waste plant materials, apple pomace (Malus domestica), wheat germs (Triticum sp.), and coffee grounds (Coffea sp.), with GluCer contents of 28.9 mg, 33.7 mg, and 4.4 mg per 100 g of plant material. Forty-five species of GluCers (1–45) were identified with different sphingoid bases, saturated or monounsaturated α-hydroxy fatty acids (C15–28), and β-glucose as polar headgroup. Three main GluCers were hydrolyzed by a recombinant human glucocerebrosidase to produce phyto-Cers (46–48). These studies showed that rare and expensive phyto-Cers can be obtained from industrial food plant residues.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 926
TI  - Altered protein expression pattern in colon tissue of mice upon supplementation with distinct selenium compounds
JO  - Proteomics
PY  - 2017
SP  - 1600486
AU  - Rahn, J.
AU  - Lennicke, C.
AU  - Kipp, A. P.
AU  - Müller, A. S.
AU  - Wessjohann, L. A.
AU  - Lichtenfels, R.
AU  - Seliger, B.
AU  - 
VL  - 17
UR  - 
DO  - 10.1002/pmic.201600486
AB  - The essential trace element selenium (Se) is controversially discussed concerning its role in health and disease. Its various physiological functions are largely mediated by Se incorporation in the catalytic center of selenoproteins. In order to gain insights into the impact of Se deficiency and of supplementation with different Se compounds (selenite, selenate, selenomethionine) at defined concentrations (recommended, 150 μg/kg diet; excessive, 750 μg/kg diet) in murine colon tissues, a 20‐week feeding experiment was performed followed by analysis of the protein expression pattern of colon tissue specimens by 2D‐DIGE and MALDI‐TOF MS. Using this approach, 24 protein spots were identified to be significantly regulated by the different Se compounds. These included the antioxidant enzyme peroxiredoxin‐5 (PRDX5), proteins with binding capabilities, such as cofilin‐1 (COF1), calmodulin, and annexin A2 (ANXA2), and proteins involved in catalytic processes, such as 6‐phosphogluconate dehydrogenase (6PGD). Furthermore, the Se compounds demonstrated a differential impact on the expression of the identified proteins. Selected target structures were validated by qPCR and Western blot which mainly confirmed the proteomic profiling data. Thus, novel Se‐regulated proteins in colon tissues have been identified, which expand our understanding of the physiologic role of Se in colon tissue.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 925
TI  - Total Synthesis of Cordyheptapeptide A
JO  - Synlett
PY  - 2017
SP  - 1971-1974
AU  - Puentes, A. R.
AU  - Neves Filho, R. A. W.
AU  - Rivera, D. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 28
UR  - 
DO  - 10.1055/s-0036-1588433
AB  - The first total synthesis of cordyheptapeptide A is described. The synthesis is accomplished by a convergent approach featuring a combination of peptide coupling and the Ugi reaction for the preparation of the main building blocks and the acyclic precursor. The assembly of an N-methylated fragment by the Ugi reaction comprised the utilization of a convertible isonitrile followed by activation of the C-terminal amide. Two different macrocyclization sites were evaluated, proving greater efficacy the macrolactamization at the site Ile-Tyr, likely due of a more suitable conformational bias of the acyclic precursor having an internal β-turn centered at the N-Me-d-Phe-Pro moiety.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 924
TI  - Peptide Macrocyclization Assisted by Traceless Turn Inducers Derived from Ugi Peptide Ligation with Cleavable and Resin-Linked Amines
JO  - Org. Lett.
PY  - 2017
SP  - 4022-4025
AU  - Puentes, A. R.
AU  - Morejon, M. C.
AU  - Rivera, D. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 19
UR  - 
DO  - 10.1021/acs.orglett.7b01761
AB  - A multicomponent approach enabling the installation of turn-inducing moieties that facilitate the macrocyclization of short and medium-size oligopeptides is described. The strategy comprises the Ugi ligation of peptide carboxylic acids and isocyanopeptides in the presence of aldehydes and acid or photolabile amines followed by cyclization and cleavage of the backbone N-substituents to render canonical cyclopeptides. Implementing the approach on solid phase with the use of Rink amide resins led to a new class of backbone amide linker strategy.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 923
TI  - Antiproliferative Activity of Gold(III) Complexes with Esters of Cyclohexyl-Functionalized Ethylenediamine-N,N’-Diacetate
JO  - Serb. J. Exp. Clin. Res.
PY  - 2017
SP  - 289-294
AU  - Pantelić, N.
AU  - Stanojković, T. P.
AU  - Zmejkovski, B. B.
AU  - Kaluđerović, G. N.
AU  - Sabo, T. J.
AU  - 
VL  - 18
UR  - 
DO  - 10.1515/sjecr-2017-0067
AB  - Six gold(III) complexes with esters of cyclohexyl-functionalized ethylenediamine-N,N’-diacetate, general formula [AuCl2{(S,S)-R2eddch}]PF6, [(S,S)-eddch = (S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate, R = Me, Et, n-Pr, n-Bu, i-Bu, i-Am, 1–6, respectively], were tested against cancer cell lines such as human melanoma Fem-x, human colon carcinoma LS174T and non-small cell lung carcinoma A549 as well as a non-cancerous human embryonic lung fibroblasts MRC-5 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with the aim of assessing in vitro antitumoral activity and selectivity. All investigated complexes showed lower cytotoxicity and better or similar selectivity in comparison to cisplatin, used as reference compound. Complex [AuCl2{(S,S)-(i-Am)2eddch}]PF6 (6) demonstrated the highest activity against Fem-x (IC50 = 14.98 ± 0.34 μM). Additionally, the same complex expressed 4.5 times higher selectivity than cisplatin.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 922
TI  - In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N′-ethylenediamine bidentate ester ligands
JO  - J. Inorg. Biochem.
PY  - 2017
SP  - 55-66
AU  - Pantelić, N.
AU  - Zmejkovski, B. B.
AU  - Kolundžija, B.
AU  - Crnogorac, M. ?.
AU  - Vujić, J. M.
AU  - Dojčinović, B.
AU  - Trifunović, S. R.
AU  - Stanojković, T. P.
AU  - Sabo, T. J.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 172
UR  - 
DO  - 10.1016/j.jinorgbio.2017.04.001
AB  - Four novel gold(III) complexes of general formulae [AuCl2{(S,S)-R2eddl}]PF6 (R2eddl = O,O′-dialkyl-(S,S)-ethylenediamine-N,N′-di-2-(4-methyl)pentanoate, R = n-Pr, n-Bu, n-Pe, i-Bu; 1–4, respectively), were synthesized and characterized by elemental analysis, UV/Vis, IR, and NMR spectroscopy, as well as high resolution mass spectrometry. Density functional theory calculations pointed out that (R,R)-N,N′-configuration diastereoisomers were energetically the most favorable. Duo to high cytotoxic activity complex 3 was chosen for stability study in DMSO, no decomposition occurs within 24 h, and for the reaction with ascorbic acid in which was reduced immediately. Additionally, 3 interacts with bovine serum albumin (BSA) as proven by UV/Vis spectroscopy. In vitro antitumor activity was determined against human cervix adenocarcinoma (HeLa), human myelogenous leukemia (K562), and human melanoma (Fem-x) cancer cell lines, as well as against non-cancerous human embryonic lung fibroblast cells MRC-5. The highest activity was observed against K562 cells (IC50: 5.04–6.51 μM). Selectivity indices showed that these complexes are less toxic than cisplatin. 3 had a similar viability kinetics on HeLa cells as cisplatin. Drug accumulation studies in HeLa cells showed that the total gold uptake increased much faster than that of cisplatin pointing out that 3 more efficiently enters the cells than cisplatin. Furthermore, morphological and cell cycle analysis reveal that gold(III) complexes induced apoptosis in time- and dose-dependent manner.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 920
TI  - Structural and stereochemical elucidation of new hygrophorones from Hygrophorus abieticola (Basidiomycetes)
JO  - Tetrahedron
PY  - 2017
SP  - 1682-1690
AU  - Otto, A.
AU  - Porzel, A.
AU  - Westermann, B.
AU  - Brandt, W.
AU  - Wessjohann, L.
AU  - Arnold, N.
AU  - 
VL  - 73
UR  - 
DO  - 10.1016/j.tet.2017.02.013
AB  - Four new hygrophorones (1–4) together with the known hygrophorone B12 (5) have been isolated from fruiting bodies of the basidiomycete Hygrophorus abieticola Krieglst. ex Gröger &amp; Bresinsky. Their structures were assigned on the basis of extensive one and two dimensional NMR spectroscopic analyses as well as ESI-HRMS measurements. Among these compounds, two previously undescribed hygrophorone types, named hygrophorone H12 (3) and 2,3-dihydrohygrophorone H12 (4), were identified. The absolute configuration of hygrophorone E12 (2) is suggested based on quantum chemical CD calculations, while a semisynthetic approach in conjunction with computational studies and analysis of NOE interactions allowed the stereochemical assignment of compounds 3 and 4. Additionally, semisynthetic derivatives of hygrophorone B12 (5) were generated by acetylation of the hydroxyl groups. The biological activity of the natural and semisynthetic hygrophorones was evaluated against phytopathogenic organisms, revealing that the α,β-unsaturated carbonyl functionality is likely to be an essential structural feature. Hygrophorone B12 (5) was identified as the most active compound, acting against both ascomycetous fungi and oomycetes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 917
TI  - Reconstitution of Vanadium Haloperoxidase&#39;s Catalytic Activity by Boric Acid-Towards a Potential Biocatalytic Role of Boron
JO  - Chem.-Eur. J.
PY  - 2017
SP  - 4973-4980
AU  - Natalio, F.
AU  - Wiese, S.
AU  - Brandt, W.
AU  - Wessjohann, L.
AU  - 
VL  - 23
UR  - 
DO  - 10.1002/chem.201605230
AB  - Boron&#39;s unusual properties inspired major advances in chemistry. In nature, the existence and importance of boron has been fairly explored (e.g. bacterial signaling, plant development) but its role as biological catalyst was never reported. Here, we show that boric acid [B(OH)3] can restore chloroperoxidase activity of Curvularia inaequalis recombinant apo‐haloperoxidase&#39;s (HPO) in the presence of hydrogen peroxide and chloride ions. Molecular modeling and semi‐empirical PM7 calculations support a thermodynamically highly favored (bio)catalytic mechanism similarly to vanadium haloperoxidases (V‐HPO) in which [B(OH)3] is assumedly located in apo‐HPO&#39;s active site and a monoperoxyborate [B(OH)3(OOH)−] intermediate is formed and stabilized by interaction with specific active site amino acids leading ultimately to the formation of HOCl. Thus, B(OH)3−HPO provides the first evidence towards the future exploitation of boron′s role in biological systems.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 915
TI  - A multicomponent macrocyclization strategy to natural product-like cyclic lipopeptides: synthesis and anticancer evaluation of surfactin and mycosubtilin analogues
JO  - Org. Biomol. Chem.
PY  - 2017
SP  - 3628-3637
AU  - Morejon, M. C.
AU  - Laub, A.
AU  - Kaluđerović, G. N.
AU  - Puentes, A. R.
AU  - Hmedat, A. N.
AU  - Otero-González, A. J.
AU  - Rivera, D. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 15
UR  - 
DO  - 10.1039/C7OB00459A
AB  - A multicomponent macrocyclization strategy towards cyclic lipopeptides is described. The approach relies on the utilization of the Ugi and Passerini multicomponent reactions for the cyclization of peptides and oxo-peptides, and here it is employed for the construction of a small library of analogues of the natural products mycosubtilin and surfactin A. A key feature of this method is the simultaneous incorporation of either one or two exocyclic lipid tails along with the macrocyclic ring closure, which is only possible due to the multicomponent nature of the macrocyclization step. The evaluation of the anticancer activity of the lipopeptide library showed that the installation of a second lipid moiety in the surfactin scaffold leads to a more potent cytotoxicity in cancer cells. This is a new example of the multicomponent reaction potential in rapidly producing natural product analogues for biological screening.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 913
TI  - Antiplasmodial Compounds from Leaves of Dodonaea angustifolia
JO  - Curr. Bioact. Comp.
PY  - 2017
SP  - 268-273
AU  - Melaku, Y.
AU  - Worku, T.
AU  - Tadesse, Y.
AU  - Mekonnen, Y.
AU  - Schmidt, J.
AU  - Arnold, N.
AU  - Dagne, E.
AU  - 
VL  - 13
UR  - 
DO  - 10.2174/1573407213666170403121222
AB  - Background: Dodonaea angustifolia is used in Ethiopian traditional medicine to treat malaria. The objective of this work was to conduct bioassay guided fractionation of the leaves of D. angustifolia using Plasmodium berghei infected mice.Method: The antiplasmodial activity of the extracts and pure compounds was evaluated using the standard Peter’s four-day suppressive method. The structures of isolated compounds were elucidated using chemical and spectroscopic methods.Results: In this study, the ethyl acetate soluble portion of the 80% aqueous MeOH extract of the leaves significantly suppressed parasitaemia in Plasmodium berghei infected mice (80.28% at 150 mg/kg). Three active compounds which exhibited significant percent suppression of parasitaemia by 81% at 40 mg/kg, 80% at 50 mg/kg and 70% at 40 mg/kg, respectively were identified. These are the flavanone pinocembrin (1), the flavanol santin (2) and the clerodane diterpene 2-hydroxy-15,16-epoxyceloda-3,13(16),14-trien-18-oic acid (3). Under similar conditions, chloroquine suppressed parasitaemia by 100% at 25 mg/kg. Chemical study of the ethanol extract of the leaves yielded 5,7,4&#39;-trihydroxy-3,6-dimethoxyflavone (4), ent-16-hydroxy-labdan-3,8-dihydroxy,13(14)-en-15,16-olide (5) and 5,6,7-trihydroxy-3,4&#39;-dimethoxyflavone (6). Compound 6 has not been reported before as a natural product.Conclusion: From the leaves of D. angustifolia, three compounds with significant antiplasmodial activities were isolated and characterized, with pinocembrin as the most active compound.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 912
TI  - Analysis of the husk and kernel of the seeds of Moringa stenopetala
JO  - Bull. Chem. Soc. Ethiop.
PY  - 2017
SP  - 107-113
AU  - Melaku, Y.
AU  - Arnold, N.
AU  - Schmidt, J.
AU  - Dagne, E.
AU  - 
VL  - 31
UR  - 
DO  - 10.4314/bcse.v31i1.9
AB  - The ethanol extract of the kernel of the endemic plant Moringa stenopetala after silica gel column chromatography led to the isolation of 4-(α-L-rhamnopyranosyloxy)benzyl glucosinolate (1) and sucrose. The oil obtained by Soxhlet extraction with petrol was trans-esterified with BF3-MeOH and analyzed by GC-MS. The results showed the presence of diverse fatty acids namely palmitic (11%), palmitoleic (1.2%), stearic (11%), oleic (63%), linoleic (1.2%), arachidic (6%) and the rare behenic acids (6%). The white glossy seed husk which comprises 25% of the whole seed yielded two compounds namely 4-(σ-L-rhamnosyloxy)benzyl alcohol (2) and allantoin (3). To the best of our knowledge this is the first report of compound 2 as a natural product. Allantoin is reported here for the first time from the genus Moringa.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 909
TI  - The choroid plexus in health and in disease: dialogues into and out of the brain
JO  - Neurobiol. Dis.
PY  - 2017
SP  - 32-40
AU  - Marques, F.
AU  - Sousa, J. C.
AU  - Brito, M. A.
AU  - Pahnke, J.
AU  - Santos, C.
AU  - Correia-Neves, M.
AU  - Palha, J. A.
AU  - 
VL  - 107
UR  - 
DO  - 10.1016/j.nbd.2016.08.011
AB  - This article brings the choroid plexus into the context of health and disease. It is remarkable that the choroid plexus, composed by a monolayer of epithelial cells that lie in a highly vascularized stroma, floating within the brain ventricles, gets so little attention in major physiology and medicine text books and in the scientific literature in general. Consider that it is responsible for producing most of the about 150 mL of cerebrospinal fluid that fills the brain ventricles and the subarachnoid space and surrounds the spinal cord in the adult human central nervous system, which is renewed approximately 2–3 times daily. As such, its activity influences brain metabolism and function, which will be addressed. Reflect that it contains an impressive number of receptors and transporters, both in the apical and basolateral sides of the epithelial cells, and as such is a key structure for the communication between the brain and the periphery. This will be highlighted in the context of neonatal jaundice, multiple sclerosis and Alzheimer&#39;s disease. Realize that the capillaries that irrigate the choroid plexus stroma do not possess tight junctions and that the blood flow to the choroid plexus is five times higher than that in the brain parenchyma, allowing for a rapid sensing system and delivery of molecules such as nutrients and metals as will be revised. Recognize that certain drugs reach the brain parenchyma solely through the choroid plexus epithelia, which has potential to be manipulated in diseases such as neonatal jaundice and Alzheimer&#39;s disease as will be discussed. Without further notice, it must be now clear that understanding the choroid plexus is necessary for comprehending the brain and how the brain is modulated and modulates all other systems, in health and in disease. This review article intends to address current knowledge on the choroid plexus, and to motivate the scientific community to consider it when studying normal brain physiology and diseases of the central nervous system. It will guide the reader through several aspects of the choroid plexus in normal physiology, in diseases characteristic of various periods of life (newborns-kernicterus, young adults-multiple sclerosis and the elder-Alzheimer&#39;s disease), and how sex-differences may relate to disease susceptibility.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 907
TI  - Repurposing N,N&#39;-bis-(arylamidino)-1,4-piperazinedicarboxamidines: An unexpected class of potent inhibitors of cholinesterases
JO  - Eur. J. Med. Chem.
PY  - 2017
SP  - 430-434
AU  - Loesche, A.
AU  - Wiese, J.
AU  - Sommerwerk, S.
AU  - Simon, V.
AU  - Brandt, W.
AU  - Csuk, R.
AU  - 
VL  - 125
UR  - 
DO  - 10.1016/j.ejmech.2016.09.051
AB  - Drug repurposing (=drug repositioning) is an effective way to cut costs for the development of new therapeutics and to reduce the time-to-market time-span. Following this concept a small library of compounds was screened for their ability to act as inhibitors of acetyl- and butyrylcholinesterase. Picloxydine, an established antiseptic, was shown to be an inhibitor for both enzymes. Systematic variation of the aryl substituents led to analogs possessing almost the same good properties as gold standard galantamine hydrobromide.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 905
TI  - Modulation of MHC class I surface expression in B16F10 melanoma cells by methylseleninic acid
JO  - OncoImmunology
PY  - 2017
SP  - e1259049
AU  - Lennicke, C.
AU  - Rahn, J.
AU  - Bukur, J.
AU  - Hochgräfe, F.
AU  - Wessjohann, L. A.
AU  - Lichtenfels, R.
AU  - Seliger, B.
AU  - 
VL  - 6
UR  - 
DO  - 10.1080/2162402X.2016.1259049
AB  - The essential trace element selenium (Se) might play a role in cancer prevention as well as for cancer therapy. Its metabolite methylselenol is able to kill cells through distinct mechanisms including induction of reactive oxygen species, DNA damage and apoptosis. Since methylselenol affects innate immune responses by modulating the expression of NKG2D ligands, the aim of this study was to determine whether the methylselenol generating compound methylseleninic acid (MSA) influences the expression of the MHC class I surface antigens and growth properties thereby reverting immune escape.Treatment of B16F10 melanoma cells expressing low basal MHC class I surface antigens with dimethyldiselenide (DMDSe) and MSA, but not with selenomethionine and selenite resulted in a dose-dependent upregulation of MHC class I cell surface antigens. This was due to a transcriptional upregulation of some major components of the antigen processing machinery (APM) and the interferon (IFN) signaling pathway and accompanied by a reduced migration of B16F10 melanoma cells in the presence of MSA. Comparative “ome”-based profilings of untreated and MSA-treated melanoma cells linked the anti-oxidative response system with MHC class I antigen processing. Since MSA treatment enhanced MHC class I surface expression also on different human tumors cell lines, MSA might affect the malignant phenotype of various tumor cells by restoring MHC class I APM component expression due to an altered redox status and by partially mimicking IFN-gamma signaling thereby providing a novel mechanism for the chemotherapeutic potential of methylselenol generating Se compounds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 904
TI  - Individual effects of different selenocompounds on the hepatic proteome and energy metabolism of mice
JO  - BBA-Gen. Subjects
PY  - 2017
SP  - 3323-3334
AU  - Lennicke, C.
AU  - Rahn, J.
AU  - Kipp, A. P.
AU  - Dojčinović, B. P.
AU  - Müller, A. S.
AU  - Wessjohann, L. A.
AU  - Lichtenfels, R.
AU  - Seliger, B.
AU  - 
VL  - 1861
UR  - 
DO  - 10.1016/j.bbagen.2016.08.015
AB  - BackgroundSelenium (Se) exerts its biological activity largely via selenoproteins, which are key enzymes for maintaining the cellular redox homeostasis. However, besides these beneficial effects there is also evidence that an oversupply of Se might increase the risk towards developing metabolic disorders. To address this in more detail, we directly compared effects of feeding distinct Se compounds and concentrations on hepatic metabolism and expression profiles of mice.MethodsMale C57BL6/J mice received either a selenium-deficient diet or diets enriched with adequate or high doses of selenite, selenate or selenomethionine for 20 weeks. Subsequently, metabolic parameters, enzymatic activities and expression levels of hepatic selenoproteins, Nrf2 targets, and additional redox-sensitive proteins were analyzed. Furthermore, 2D-DIGE-based proteomic profiling revealed Se compound-specific differentially expressed proteins.ResultsWhereas heterogeneous effects between high concentrations of the Se compounds were observed with regard to body weight and metabolic activities, selenoproteins were only marginally increased by high Se concentrations in comparison to the respective adequate feeding. In particular the high-SeMet group showed a unique response compromising higher hepatic Se levels in comparison to all other groups. Accordingly, hepatic glutathione (GSH) levels, glutathione S-transferase (GST) activity, and GSTpi1 expression were comparably high in the high-SeMet and Se-deficient group, indicating that compound-specific effects of high doses appear to be independent of selenoproteins.ConclusionsNot only the nature, but also the concentration of Se compounds differentially affect biological processes.General significanceThus, it is important to consider Se compound-specific effects when supplementing with selenium.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 901
TI  - In vitro cytotoxicity of compounds isolated from Desbordesia glaucescens against human carcinoma cell lines
JO  - S. Afr. J. Bot.
PY  - 2017
SP  - 37-43
AU  - Kuete, V.
AU  - Dongmo Mafodong, F. L.
AU  - Celik, I.
AU  - Fobofou, S. A. T.
AU  - Ndontsa, B. L.
AU  - Karaosmanoğlu, O.
AU  - Wessjohann, L. A.
AU  - Tane, P.
AU  - Koparal, A. T.
AU  - Sivas, H.
AU  - 
VL  - 111
UR  - 
DO  - 10.1016/j.sajb.2017.03.031
AB  - Malignancies constitute a global health concern and chemotherapy remains the main mode of treatment. The present study was designed to evaluate the cytotoxicity of 8 compounds from Desbordesia glaucescens namely lanosta-7,24-dien-3-one (1), friedelanone (2), friedelanol (3), 3,3′-di-O-methylellagic acid (4), 3,3′,4′-tri-O-methylellagic acid (5), ellagic acid (6), 3′,4′-di-O-methylellagic acid 4-O-β-d-glucopyranoside (7) and 3,3′-di-O-methylellagic acid 4′-O-β-d-xylopyranoside (8) against 4 human carcinoma cell lines and normal CRL2120 fibroblasts. The neutral red uptake (NRU) assay was used for cytotoxicity testing. Caspase-Glo assay, cell cycle analysis, measurements of mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were used to evaluate apoptosis induction. Compounds 4 and 6 as well as doxorubicin had IC50 values below 45 μM in the four tested cancer cell lines meanwhile other compounds displayed selective activity. The IC50 values ranged from 11.23 μM (towards breast adenocarcinoma MCF-7 cells) to 44.65μM (colon carcinoma Caco-2 cells) for 4, from 14.07 μM (towards MCF-7 cells) to 77.73 μM (Caco-2 cells) for 6 and from 0.07 μM (towards SPC212 cells) to 1.01 μM (A549 cells) for doxorubicin. Compound 4 induced apoptosis in MCF-7 cells mediated by MMP loss. The constituents of Desbordesia glaucescens and especially ellagic acid (6) and its derivative 4 are potential cytotoxic compounds that deserve more investigations towards developing novel antiproliferative drugs against human carcinoma.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 900
TI  - Rothtalazepane, A New Azepane from the Wood of Rothmannia talbotii (Rubiaceae)
JO  - Nat. Prod. Commun.
PY  - 2017
SP  - 1435-1436
AU  - Koagne, R. R.
AU  - Bitchagno, G. T. M.
AU  - Fobofou, S. A. T.
AU  - Konga, I. S.
AU  - Tamokou, J. d. D.
AU  - Wessjohann, L. A.
AU  - Tane, P.
AU  - 
VL  - 12
UR  - 
DO  - 10.1177/1934578X1701200912
AB  - Rothmannia talbotii, a hitherto chemically unexplored medicinal plant, is used in the Western Region of Cameroon to relieve fever. In our ongoing search for bioactive compounds from Cameroonian medicinal plants, a previously undescribed compound rothtalazepane (1), along with six known compounds, aitchisonide B (2), D-mannitol (3), β-D-glucopyranosyl-(6→1’)-β-D-glucopyranoside (4), monopalmitin (5), stigmasterol (6), and sitosterol 3-O-β-D-glucopyranoside (7) were isolated and characterized from the crude ethanol extract of the wood of R. talbotii. Rothtalazepane (1) exhibits no significant activity against several microbial strains, thus its function likely lies not in antimicrobial defense and it is not the active principle against urinary infections described for Rothmannia.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 942
TI  - Crystal and molecular structure of a new palladium(II) complex with a coumarin-valine derivate
JO  - J. Struct. Chem.
PY  - 2017
SP  - 550-557
AU  - Stojković, D. L.
AU  - Jevtić, V. V.
AU  - Vuković, N.
AU  - Vukić, M.
AU  - Potočňák, I.
AU  - Zelen, I. R.
AU  - Zarić, M. M.
AU  - Mišić, M. M.
AU  - Baskić, D.
AU  - Kaluđerović, G. N.
AU  - Trifunović, S. R.
AU  - 
VL  - 58
UR  - 
DO  - 10.1134/S0022476617030179
AB  - The new coumarine derivate with methyl ester of 2-((Z)-1(2,4-dioxochroman-3-ylidene)ethylamino)-3-methylbutanoic acid and the corresponding palladium(II) complex are synthesized and characterized by microanalysis, infrared, 1H and 13C NMR spectroscopy. The proposed structure of the ligand was confirmed based on the X-ray structural study.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 941
TI  - Expression of endogenous mouse APP modulates β-amyloid deposition in hAPP-transgenic mice
JO  - Acta Neuropathol. Commun.
PY  - 2017
SP  - 49
AU  - Steffen, J.
AU  - Krohn, M.
AU  - Schwitlick, C.
AU  - Brüning, T.
AU  - Paarmann, K.
AU  - Pietrzik, C. U.
AU  - Biverstål, H.
AU  - Jansone, B.
AU  - Langer, O.
AU  - Pahnke, J.
AU  - 
VL  - 5
UR  - 
DO  - 10.1186/s40478-017-0448-2
AB  - Amyloid-β (Aβ) deposition is one of the hallmarks of the amyloid hypothesis in Alzheimer’s disease (AD). Mouse models using APP-transgene overexpression to generate amyloid plaques have shown to model only certain parts of the disease. The extent to which the data from mice can be transferred to man remains controversial. Several studies have shown convincing treatment results in reducing Aβ and enhancing cognition in mice but failed totally in human. One model-dependent factor has so far been almost completely neglected: the endogenous expression of mouse APP and its effects on the transgenic models and the readout for therapeutic approaches.Here, we report that hAPP-transgenic models of amyloidosis devoid of endogenous mouse APP expression (mAPP-knockout / mAPPko) show increased amounts and higher speed of Aβ deposition than controls with mAPP. The number of senile plaques and the level of aggregated hAβ were elevated in mAPPko mice, while the deposition in cortical blood vessels was delayed, indicating an alteration in the general aggregation propensity of hAβ together with endogenous mAβ. Furthermore, the cellular response to Aβ deposition was modulated: mAPPko mice developed a pronounced and age-dependent astrogliosis, while microglial association to amyloid plaques was diminished. The expression of human and murine aggregation-prone proteins with differing amino acid sequences within the same mouse model might not only alter the extent of deposition but also modulate the route of pathogenesis, and thus, decisively influence the study outcome, especially in translational research.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 939
TI  - Quantification of prospective type 2 diabetes mellitus biomarkers by stable isotope dilution with bi-labeled standard glycated peptides
JO  - Anal. Methods
PY  - 2017
SP  - 409-418
AU  - Soboleva, A.
AU  - Modzel, M.
AU  - Didio, A.
AU  - Płóciennik, H.
AU  - Kijewska, M.
AU  - Grischina, T.
AU  - Karonova, T.
AU  - Bilova, T.
AU  - Stefanov, V.
AU  - Stefanowicz, P.
AU  - Frolov, A.
AU  - 
VL  - 9
UR  - 
DO  - 10.1039/C6AY02483A
AB  - Type 2 diabetes mellitus (T2DM) is a complex group of disorders, characterized by hyperglycemia, insulin resistance and insulin deficiency. In human blood, hyperglycemia ultimately results in the enhancement of glycation – a posttranslational modification formed by the interaction of protein amino groups with glucose. The resulting fructosamines (Amadori compounds) readily undergo further degradation resulting in advanced glycation end products (AGEs), known to be pro-inflammatory in humans. These compounds are highly heterogeneous and characteristic of advanced stages of the disease, whereas fructosamines are recognized markers of early diabetes stages (HbA1C, glycated albumin). Recently, individual plasma protein glycation sites were proposed as promising T2DM biomarkers sensitive to short-term fluctuations of plasma glucose. However, corresponding absolute quantification strategies, applicable in regular clinical practice, are still not established. Therefore, here we propose a new analytical approach aiming at reproducible and precise quantification of multiple glycated peptides in human plasma tryptic digests. Thereby, the standard peptides comprised a 13C,15N-labeled lysyl residue, a dabsyl moiety for determination of standard amounts, and a cleavable linker. Known amounts of these peptides were spiked to plasma samples prior to tryptic digestion, quantification relying on stable isotope dilution. The method was demonstrated to be applicable for quantification of individual glycated sites in T2DM patients and non-diabetic controls.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 938
TI  - Probing Protein Glycation by Chromatography and Mass Spectrometry: Analysis of Glycation Adducts
JO  - Int. J. Mol. Sci.
PY  - 2017
SP  - 2557
AU  - Soboleva, A.
AU  - Vikhnina, M.
AU  - Grishina, T.
AU  - Frolov, A.
AU  - 
VL  - 18
UR  - 
DO  - 10.3390/ijms18122557
AB  - Glycation is a non-enzymatic post-translational modification of proteins, formed by the reaction of reducing sugars and α-dicarbonyl products of their degradation with amino and guanidino groups of proteins. Resulted early glycation products are readily involved in further transformation, yielding a heterogeneous group of advanced glycation end products (AGEs). Their formation is associated with ageing, metabolic diseases, and thermal processing of foods. Therefore, individual glycation adducts are often considered as the markers of related pathologies and food quality. In this context, their quantification in biological and food matrices is required for diagnostics and establishment of food preparation technologies. For this, exhaustive protein hydrolysis with subsequent amino acid analysis is the strategy of choice. Thereby, multi-step enzymatic digestion procedures ensure good recoveries for the most of AGEs, whereas tandem mass spectrometry (MS/MS) in the multiple reaction monitoring (MRM) mode with stable isotope dilution or standard addition represents “a gold standard” for their quantification. Although the spectrum of quantitatively assessed AGE structures is continuously increases, application of untargeted profiling techniques for identification of new products is desired, especially for in vivo characterization of anti-glycative systems. Thereby, due to a high glycative potential of plant metabolites, more attention needs to be paid on plant-derived AGEs.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 937
TI  - Maillard Proteomics: Opening New Pages
JO  - Int. J. Mol. Sci.
PY  - 2017
SP  - 2677
AU  - Soboleva, A.
AU  - Schmidt, R.
AU  - Vikhnina, M.
AU  - Grishina, T.
AU  - Frolov, A.
AU  - 
VL  - 18
UR  - 
DO  - 10.3390/ijms18122677
AB  - Protein glycation is a ubiquitous non-enzymatic post-translational modification, formed by reaction of protein amino and guanidino groups with carbonyl compounds, presumably reducing sugars and α-dicarbonyls. Resulting advanced glycation end products (AGEs) represent a highly heterogeneous group of compounds, deleterious in mammals due to their pro-inflammatory effect, and impact in pathogenesis of diabetes mellitus, Alzheimer’s disease and ageing. The body of information on the mechanisms and pathways of AGE formation, acquired during the last decades, clearly indicates a certain site-specificity of glycation. It makes characterization of individual glycation sites a critical pre-requisite for understanding in vivo mechanisms of AGE formation and developing adequate nutritional and therapeutic approaches to reduce it in humans. In this context, proteomics is the methodology of choice to address site-specific molecular changes related to protein glycation. Therefore, here we summarize the methods of Maillard proteomics, specifically focusing on the techniques providing comprehensive structural and quantitative characterization of glycated proteome. Further, we address the novel break-through areas, recently established in the field of Maillard research, i.e., in vitro models based on synthetic peptides, site-based diagnostics of metabolism-related diseases (e.g., diabetes mellitus), proteomics of anti-glycative defense, and dynamics of plant glycated proteome during ageing and response to environmental stress.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 936
TI  - Genetic and Hormonal Regulation of Chlorophyll Degradation during Maturation of Seeds with Green Embryos
JO  - Int. J. Mol. Sci.
PY  - 2017
SP  - 1993
AU  - Smolikova, G.
AU  - Dolgikh, E.
AU  - Vikhnina, M.
AU  - Frolov, A.
AU  - Medvedev, S.
AU  - 
VL  - 18
UR  - 
DO  - 10.3390/ijms18091993
AB  - The embryos of some angiosperms (usually referred to as chloroembryos) contain chlorophylls during the whole period of embryogenesis. Developing embryos have photochemically active chloroplasts and are able to produce assimilates, further converted in reserve biopolymers, whereas at the late steps of embryogenesis, seeds undergo dehydration, degradation of chlorophylls, transformation of chloroplast in storage plastids, and enter the dormancy period. However, in some seeds, the process of chlorophyll degradation remains incomplete. These residual chlorophylls compromise the quality of seed material in terms of viability, nutritional value, and shelf life, and represent a serious challenge for breeders and farmers. The mechanisms of chlorophyll degradation during seed maturation are still not completely understood, and only during the recent decades the main pathways and corresponding enzymes could be characterized. Among the identified players, the enzymes of pheophorbide a oxygenase pathway and the proteins encoded by STAY GREEN (SGR) genes are the principle ones. On the biochemical level, abscisic acid (ABA) is the main regulator of seed chlorophyll degradation, mediating activity of corresponding catabolic enzymes on the transcriptional level. In general, a deep insight in the mechanisms of chlorophyll degradation is required to develop the approaches for production of chlorophyll-free high quality seeds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 935
TI  - Improved method for cannula fixation for long-term intracerebral brain infusion
JO  - J. Neurosci. Meth.
PY  - 2017
SP  - 145-150
AU  - Sike, ?.
AU  - Wengenroth, J.
AU  - Upīte, J.
AU  - Brüning, T.
AU  - Eiriz, I.
AU  - Sántha, P.
AU  - Biverstål, H.
AU  - Jansone, B.
AU  - Haugen, H. J.
AU  - Krohn, M.
AU  - Pahnke, J.
AU  - 
VL  - 290
UR  - 
DO  - 10.1016/j.jneumeth.2017.07.026
AB  - BackgroundImplanted osmotic minipumps are commonly used for long-term, brain-targeted delivery of a wide range of experimental agents by being connected to a catheter and a cannula. During the stereotactical surgery procedure, the cannula has to be placed correctly in the x-y directions and also with respect to the injection point in the z-direction (deepness). However, the flat fixation base of available cannula holders doesn’t allow an easy, secure fixation onto the curve-shaped skull.New methodWe have developed a modified method for a better fixation of the cannula holder by using an easy-to-produce, skull-shaped silicone spacer as fixation adapter.ResultsWe describe the application and its fast and reliable production in the lab.Comparison with existing method(s)Superglue or cement is currently being used as the method of choice. However, the curve-shaped skull surface does not fit well with the flat and rigid cannula adapter which leads to fixation problems over time causing wide infusion channels and often also to leakage problems from intracerebrally applied agents towards the surface meninges. As another consequence of the inappropriate fixation, the cannula may loosen from the skull before the end of the experiment or it causes damage to the brain tissue, harming the animals with leading to a failure of the whole experiment.ConclusionsThe easy-to-produce spacer facilitates the crucial step of long-term, stereotactic brain infusion experiments with intracerebral catheters in a highly secure and reproducible way.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 931
TI  - Leaf litter diversity positively affects the decomposition of plant polyphenols
JO  - Plant Soil
PY  - 2017
SP  - 305-317
AU  - Ristok, C.
AU  - Leppert, K. N.
AU  - Franke, K.
AU  - Scherer-Lorenzen, M.
AU  - Niklaus, P. A.
AU  - Wessjohann, L. A.
AU  - Bruelheide, H.
AU  - 
VL  - 419
UR  - 
DO  - 10.1007/s11104-017-3340-8
AB  - Background and AimsLeaf litter decomposition is closely linked to nutrient cycling and driven by environmental conditions, species-specific leaf chemistry, and here in particular by polyphenols composition. However, not much attention has been paid on the decomposition of polyphenols themselves. We hypothesized that phenolics and tannin decomposition rates are species-specific and positively affected by litter species richness.MethodsLeaf litter of three Chinese tree species was exposed to field decomposition conditions, aggregated in mixtures of different species richness (1-, 2-, 3-species mixtures). We sampled litter five times over the course of 171 days, calculated species-specific total phenolics and total protein precipitable tannin decomposition rates, assessed changes in polyphenol composition using HPLC, and tentatively identified compounds by LC-ESI-MS/MS.ResultsLeaf litter richness effects on phenolics and tannin decomposition rates were positive, except for Sapindus-specific tannins, and differed between leaf litter species. Decomposition duration changed polyphenol compositions, and significantly interacted with leaf litter species richness with increasing effects of litter richness with time.ConclusionsLitter diversity effects on polyphenol decomposition are crucial for whole leaf litter decomposition. The contrasting dependencies of phenolics and tannin decomposition rates on leaf litter richness may provide explanations for equivocal results in leaf litter mixture experiments.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 899
TI  - Silicon-based nanotheranostics
JO  - Nanoscale
PY  - 2017
SP  - 12821-12829
AU  - Knežević, N. ?.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 9
UR  - 
DO  - 10.1039/C7NR04445C
AB  - With the rapid expansion of nanoscience and nanotechnology in interdisciplinary fields, multifunctional nanomaterials have attracted particular attention. Recent advances in nanotherapeutics for cancer applications provided diverse groups of synthetic particles with defined cellular and biological functions. The advance of nanotechnology significantly increased the number of possibilities for the construction of diverse biological tools. Such materials are destined to be of great importance because of the opportunity to combine the biotechnological potential of nanoparticles together with the recognition, sensitivity and modulation of cellular pathways or genes when applied to living organisms. In this mini review three main types of Si-based nanomaterials are highlighted in the area of their application for therapy and imaging: porous silicon nanoparticles (pSiNPs), mesoporous silica nanoparticles (MSNs), focusing on their nanoconstructs containing coordination compounds, and periodic mesoporous silica nanoparticles (PMONPs). Moreover, a critical discussion on the research efforts in the construction of nanotheranostics is presented.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 897
TI  - Methionine and seleno-methionine type peptide and peptoid building blocks synthesized by five-component five-center reactions
JO  - Chem. Commun.
PY  - 2017
SP  - 3777-3780
AU  - Kaluđerović, G. N.
AU  - Abbas, M.
AU  - Kautz, H. C.
AU  - Wadaan, M. A. M.
AU  - Lennicke, C.
AU  - Seliger, B.
AU  - Wessjohann, L. A.
AU  - 
VL  - 53
UR  - 
DO  - 10.1039/C7CC00399D
AB  - A first example of 5-component 5-center reactions with isonitriles [Ugi-5CRs] is described. The extended Ugi type reactions involve selenoaldehydes as well as ammonia, both challenging reactants in multicomponent (MCR) systems, to generate methionine and Se-methionine moieties and derivatives as protected building blocks or for direct ligation in peptides or peptoids. The peptoid/peptide building blocks proved to be non-cytotoxic but increased the expression of genes encoding for stress protective selenoproteins (Gpx1).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 896
TI  - (18-Crown-6)potassium(I) Trichlorido[28-acetyl-3-(tris-(hydroxylmethyl)amino-ethane)betulinic ester-κN]platinum(II): Synthesis and In Vitro Antitumor Activity
JO  - Inorganics
PY  - 2017
SP  - 56
AU  - Kaluđerović, G. N.
AU  - Bulatović, M.
AU  - Krajnović, T.
AU  - Paschke, R.
AU  - Zmejkovski, B. B.
AU  - Maksimović-Ivanić, D.
AU  - Mijatović, S.
AU  - 
VL  - 5
UR  - 
DO  - 10.3390/inorganics5030056
AB  - Synthesis of platinum(II) conjugate with acetylated betulinic acid tris(hydroxymethyl)aminomethane ester (BATRIS) is presented (BATRISPt). HR-ESI-MS and multinuclear NMR spectroscopy, as well as elemental analysis were used for characterization of BATRISPt. Cytotoxicity (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), crystal violet (CV), and sulforhodamine B (SRB) assays) of BA, BATRIS, BATRISPt, and cisplatin were assessed on seven different tumor cell lines: melanoma B16, colon HCT116 and DLD-1, adenocarcinoma HeLa, breast MCF-7, and anaplastic thyroid tumor 8505C and SW1736; as well as normal MRC-5 fibroblasts. Furthermore, the effect of the mentioned compounds on the apoptosis (Annexin V/PI assay) and autophagy induction (acridine orange (AO) assay) as well as caspase 3, 8, and 9 activation were investigated on the selected B16 melanoma cell line. BATRISPt showed lower activity than BA, BATRIS, or cisplatin. All tested compounds triggered apoptosis in B16 cells. Induction of autophagy was observed in B16 cells exposed only to BATRIS. On the other hand, new conjugate activates caspases 8 and 9 in B16 cells with higher impact than BATRIS or cisplatin alone.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 895
TI  - Mesoporous silica nanoparticles SBA-15 loaded with emodin upregulate the antioxidative defense of Euproctis chrysorrhoea (L.) larvae
JO  - Turk. J. Biol.
PY  - 2017
SP  - 935-942
AU  - Janković-Tomanić, M.
AU  - Todorović, D.
AU  - Stanivuković, Z.
AU  - Perić Mataruga, V.
AU  - Wessjohann, L. A.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 41
UR  - 
DO  - 10.3906/biy-1705-76
AB  - The study presented here aims to elucidate the effects of emodin (EO = 1,3,8-trihydroxy-6-methylanthraquinone) in its freeform and when loaded into a mesoporous silica nanocarrier SBA-15 (→ SBA-15&#124;EO) on the activities of the main antioxidative enzymes,superoxide dismutase, catalase, glutathione S-transferase, and glutathione reductase, in larvae of a polyphagous insect pest, the browntailmoth Euproctis chrysorrhoea (L.). The results show that only SBA-15&#124;EO upregulates the activities of the tested antioxidative enzymes.These results point to significant differences in the effectiveness of the compound in the free versus the loaded form.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 891
TI  - Anionic chlorido(triphenyl)tin(IV) bearing N-phthaloylglycinato or 1,2,4-benzenetricarboxylato 1,2-anhydride ligands: potential cytotoxic and apoptosis-inducing agents against several types of cancer
JO  - Chem. Biol. Drug Des.
PY  - 2017
SP  - 628-633
AU  - Hübner, D.
AU  - Kaluđerović, M. R.
AU  - Gómez-Ruiz, S.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 89
UR  - 
DO  - 10.1111/cbdd.12885
AB  - Two ionic triphenyltin(IV) chloride carboxylate compounds of the formula [NHEt3][Ph3SnCl(L)] [LH = N‐phthaloylglycine (P‐GlyH), 1; 1,2,4‐benzenetricarboxylic 1,2‐anhydride (BTCH), 2] were tested for the in vitro activity against 518A2 (melanoma), FaDu (head and neck carcinoma), HT‐29 (colon cancer), MCF‐7 (breast carcinoma), and SW1736 (thyroid cancer) cell lines. The ammonium salts of the carboxylic acids are found to be not active, while anionic [Ph3SnCl(L)]− exhibited high cytotoxicity in nM range, both higher activity and selectivity than cisplatin. Compounds 1 and 2 are inducing apoptosis, which was proved with the morphological and biochemical features such as membrane blebbing, translocation of phosphatidylserine, and DNA fragmentation. Thus, accumulation of cells in sub‐G1 phase is observed. Both anionic organotin(IV) compounds showed potent cytotoxic and apoptotic properties against five cancer cell lines of various histogenetic origin.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 887
TI  - Amino derivatives of platanic acid act as selective and potent inhibitors of butyrylcholinesterase
JO  - Eur. J. Med. Chem.
PY  - 2017
SP  - 652-668
AU  - Heller, L.
AU  - Kahnt, M.
AU  - Loesche, A.
AU  - Grabandt, P.
AU  - Schwarz, S.
AU  - Brandt, W.
AU  - Csuk, R.
AU  - 
VL  - 126
UR  - 
DO  - 10.1016/j.ejmech.2016.11.056
AB  - A set of thirtyfive 30-norlupan derivatives (2–36) was prepared from the natural triterpenoid platanic acid (PA), and the hydroxyl group at C-3, the carboxyl group at C-17 and the carbonyl group at C-20 were modified. These derivatives were tested for their inhibitory activity for the enzymes acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum) using Ellman&#39;s assay. Extra enzyme kinetic studies were performed. The most active compound was (3β, 20R)-3-acetyloxy-20-amino-30-norlupan-28-oate (32) showing a Ki value of 0.01 ± 0.003 μM for BChE. This compound proved to be a selective (FB = 851), mixed-type inhibitor for BChE.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 886
TI  - Pigment pattern of the Chilean mushroom Dermocybe nahuelbutensis Garrido &amp; E. Horak
JO  - Rec. Nat. Prod.
PY  - 2017
SP  - 547-551
AU  - Greff, A.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Palfner, G.
AU  - Arnold, N.
AU  - 
VL  - 11
UR  - 
DO  - 10.25135/rnp.69.17.01.027
AB  - Fruiting bodies of the Chilean mushroom Dermocybe nahuelbutenis Garrido &amp; E. Horak (syn.: Cortinariusnahuelbutensis (Garrido &amp; E. Horak) E. Valenz. &amp; G. Moreno) were chemically investigated for the first time andafforded the new dimeric anthraqinone 7,7&#39;-emodinphyscion (1) beside the know anthraquinones dermolutein (2),endocrocin (3), skyrin (4) and the dimeric pre-anthraquinone derivative flavomannin C (5). The chemotaxonomicsignificance of the pigments is discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 882
TI  - Early responses of mature Arabidopsis thaliana plants to reduced water potential in the agar-based polyethylene glycol infusion drought model
JO  - J. Plant Physiol.
PY  - 2017
SP  - 70-83
AU  - Frolov, A.
AU  - Bilova, T.
AU  - Paudel, G.
AU  - Berger, R.
AU  - Balcke, G. U.
AU  - Birkemeyer, C.
AU  - Wessjohann, L. A.
AU  - 
VL  - 208
UR  - 
DO  - 10.1016/j.jplph.2016.09.013
AB  - Drought is one of the most important environmental stressors resulting in increasing losses of crop plant productivity all over the world. Therefore, development of new approaches to increase the stress tolerance of crop plants is strongly desired. This requires precise and adequate modeling of drought stress. As this type of stress manifests itself as a steady decrease in the substrate water potential (ψw), agar plates infused with polyethylene glycol (PEG) are the perfect experimental tool: they are easy in preparation and provide a constantly reduced ψw, which is not possible in soil models. However, currently, this model is applicable only to seedlings and cannot be used for evaluation of stress responses in mature plants, which are obviously the most appropriate objects for drought tolerance research. To overcome this limitation, here we introduce a PEG-based agar infusion model suitable for 6–8-week-old A. thaliana plants, and characterize, to the best of our knowledge for the first time, the early drought stress responses of adult plants grown on PEG-infused agar. We describe essential alterations in the primary metabolome (sugars and related compounds, amino acids and polyamines) accompanied by qualitative and quantitative changes in protein patterns: up to 87 unique stress-related proteins were annotated under drought stress conditions, whereas further 84 proteins showed a change in abundance. The obtained proteome patterns differed slightly from those reported for seedlings and soil-based models.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 881
TI  - Rats’ urinary metabolomes reveal the potential roles of functional foods and exercise in obesity management
JO  - Food Funct.
PY  - 2017
SP  - 985-996
AU  - Farag, M. A.
AU  - Ammar, N. M.
AU  - Kholeif, T. E.
AU  - Metwally, N. S.
AU  - El-Sheikh, N. M.
AU  - Wessjohann, L. A.
AU  - Abdel-Hamid, A. Z.
AU  - 
VL  - 8
UR  - 
DO  - 10.1039/C6FO01753C
AB  - The complexity of the metabolic changes in obese individuals still presents a challenge for the understanding of obesity-related metabolic disruptions and for obesity management. In this study, a gas chromatography mass spectrometry (GC-MS) based metabolomics approach targeting urine metabolism has been applied to assess the potential roles of functional foods and exercise for obesity management in rats. Male albino rats diagnosed as obese via histopathology and biochemical assays were administered functional foods in common use for obesity management including pomegranate, grapefruit, and red cabbage juice extracts in parallel with swimming exercise. Urine samples were collected from these rats, and likewise from healthy control animals, for metabolite analysis using (GC-MS) coupled to multivariate data analysis. The results revealed a significant elevation in oxalate and phosphate levels in obese rat urine concurrent with lower lactate levels as compared to the control group. Furthermore, and to pinpoint the bioactive agents in the administered functional foods, ultra performance liquid chromatography (UPLC) coupled to high resolution time-of-flight mass spectrometry (TOF-MS) was employed for secondary metabolite profiling. The different phenolic classes found in the examined functional foods, viz. ellagitannins in pomegranate, flavanones in grapefruit and flavonols in red cabbage, are likely to mediate their anti-obesity effects. The results indicate that these functional foods and exercise were quite effective in reverting obesity-related metabolic disruptions back to normal status, as revealed by orthogonal partial least squares-discriminant analysis (OPLS-DA).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 880
TI  - Phytochemical Profiles and Antimicrobial Activities of Allium cepa Red cv. and A. sativum Subjected to Different Drying Methods: A Comparative MS-Based Metabolomics
JO  - Molecules
PY  - 2017
SP  - 761
AU  - Farag, M. A.
AU  - Ali, S. E.
AU  - Hodaya, R. H.
AU  - El-Seedi, H. R.
AU  - Sultani, H. N.
AU  - Laub, A.
AU  - Eissa, T. F.
AU  - Abou-Zaid, F. O. F.
AU  - Wessjohann, L. A.
AU  - 
VL  - 22
UR  - 
DO  - 10.3390/molecules22050761
AB  - Plants of the Allium genus produce sulphur compounds that give them a characteristic (alliaceous) flavour and mediate for their medicinal use. In this study, the chemical composition and antimicrobial properties of Allium cepa red cv. and A. sativum in the context of three different drying processes were assessed using metabolomics. Bulbs were dried using either microwave, air drying, or freeze drying and further subjected to chemical analysis of their composition of volatile and non-volatile metabolites. Volatiles were collected using solid phase micro-extraction (SPME) coupled to gas chromatography–mass spectrometry (GC/MS) with 42 identified volatiles including 30 sulphur compounds, four nitriles, three aromatics, and three esters. Profiling of the polar non-volatile metabolites via ultra-performance liquid chromatography coupled to high resolution MS (UPLC/MS) annotated 51 metabolites including dipeptides, flavonoids, phenolic acids, and fatty acids. Major peaks in GC/MS or UPLC/MS contributing to the discrimination between A. sativum and A. cepa red cv. were assigned to sulphur compounds and flavonoids. Whereas sulphur conjugates amounted to the major forms in A. sativum, flavonoids predominated in the chemical composition of A. cepa red cv. With regard to drying impact on Allium metabolites, notable and clear separations among specimens were revealed using principal component analysis (PCA). The PCA scores plot of the UPLC/MS dataset showed closer metabolite composition of microwave dried specimens to freeze dried ones, and distant from air dried bulbs, observed in both A. cepa and A. sativum. Compared to GC/MS, the UPLC/MS derived PCA model was more consistent and better in assessing the impact of drying on Allium metabolism. A phthalate derivative was found exclusively in a commercial garlic preparation via GC/MS, of yet unknown origin. The freeze dried samples of both Allium species exhibited stronger antimicrobial activities compared to dried specimens with A. sativum being in general more active than A. cepa red cv.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 879
TI  - Metabolomics reveals biotic and abiotic elicitor effects on the soft coral Sarcophyton ehrenbergi terpenoid content
JO  - Sci. Rep.
PY  - 2017
SP  - 648
AU  - Farag, M. A.
AU  - Al-Mahdy, D. A.
AU  - Meyer, A.
AU  - Westphal, H.
AU  - Wessjohann, L. A.
AU  - 
VL  - 7
UR  - 
DO  - 10.1038/s41598-017-00527-8
AB  - The effects of six biotic and abiotic elicitors, i.e. MeJA (methyl jasmonate), SA (salicylic acid), ZnCl2, glutathione and β-glucan BG (fungal elicitor), and wounding, on the secondary metabolite accumulation in the soft coral Sarcophyton ehrenbergi were assessed. Upon elicitation, metabolites were extracted and analysed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Except for MeJA, no differences in photosynthetic efficiency were observed after treatments, suggesting the absence of a remarkable stress on primary production. Chemometric analyses of UPLC-MS data showed clear segregation of SA and ZnCl2 elicited samples at 24 and 48 h post elicitation. Levels of acetylated diterpene and sterol viz., sarcophytonolide I and cholesteryl acetate, was increased in ZnCl2 and SA groups, respectively, suggesting an activation of specific acetyl transferases. Post elicitation, sarcophytonolide I level increased 132 and 17-folds at 48 h in 0.1 mM SA and 1 mM ZnCl2 groups, respectively. Interestingly, decrease in sarcophine, a major diterpene was observed only in response to ZnCl2, whereas no change was observed in sesquiterpene content following treatments. To the best of our knowledge, this study provides the first documentation for elicitation effects on a soft corals secondary metabolome and suggests that SA could be applied to increase diterpenoid levels in corals.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 878
TI  - Effect of Oxylipins, Terpenoid Precursors and Wounding on Soft Corals’ Secondary Metabolism as Analyzed via UPLC/MS and Chemometrics
JO  - Molecules
PY  - 2017
SP  - 2195
AU  - Farag, M. A.
AU  - Westphal, H.
AU  - Eissa, T. F.
AU  - Wessjohann, L. A.
AU  - Meyer, A.
AU  - 
VL  - 22
UR  - 
DO  - 10.3390/molecules22122195
AB  - The effect of three oxylipin analogues, a terpenoid intermediate and wounding on the secondary metabolism of the soft corals Sarcophyton glaucum and Lobophyton pauciflorum was assessed. Examined oxylipins included prostaglandin (PG-E1), methyl jasmonate (MeJA), and arachidonic acid (AA) in addition to the diterpene precursor geranylgeranylpyrophosphate (GGP). Post-elicitation, metabolites were extracted from coral heads and analyzed via UPLC-MS followed by multivariate data analyses. Both supervised and unsupervised data analyses were used for sample classification. Multivariate data analysis revealed clear segregation of PG-E1 and MeJA elicited S. glaucum at 24 and 48 h post elicitation from other elicitor samples and unelicited control group. PG-E1 was found more effective in upregulating S. glaucum terpene/sterol levels compared to MeJA. Metabolites showing upregulation in S. glaucum include campestene-triol and a cembranoid, detected at ca. 30- and 2-fold higher levels compared to unelicited corals. Such an elicitation effect was less notable in the other coral species L. pauciflorum, suggesting a differential oxylipin response in soft corals. Compared to MeJA and PG, no elicitation effect was observed for GGP, AA or wounding on the metabolism of either coral species.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 877
TI  - Cytotoxic Effects of Sarcophyton sp. Soft Corals—Is There a Correlation to Their NMR Fingerprints?
JO  - Mar. Drugs
PY  - 2017
SP  - 211
AU  - Farag, M. A.
AU  - Fekry, M. I.
AU  - Al-Hammady, M. A.
AU  - Khalil, M. N.
AU  - El-Seedi, H. R.
AU  - Meyer, A.
AU  - Porzel, A.
AU  - Westphal, H.
AU  - Wessjohann, L. A.
AU  - 
VL  - 15
UR  - 
DO  - 10.3390/md15070211
AB  - Sarcophyton sp. soft corals are rich in cembranoid diterpenes, which represent the main chemical defense of corals against their natural predators in addition to their myriad biological effects in humans. Quantitative NMR (qNMR) was applied for assessing the diterpene variation in 16 soft coral specimens in the context of their genotype, origin, and growing habitat. qNMR revealed high diterpene levels in Sarcophyton sp. compared to Sinularia and Lobophyton, with (ent)sarcophines as major components (17–100 µg/mg) of the coral tissues. Multivariate data analysis was employed to classify samples based on the quantified level of diterpenes, and compared to the untargeted NMR approach. Results revealed that qNMR provided a stronger classification model of Sarcophyton sp. than untargeted NMR fingerprinting. Additionally, cytotoxicity of soft coral crude extracts was assessed against androgen-dependent prostate cancer cell lines (PC3) and androgen-independent colon cancer cell lines (HT-29), with IC50 values ranging from 10–60 µg/mL. No obvious correlation between the extracts’ IC50 values and their diterpene levels was found using either Spearman or Pearson correlations. This suggests that this type of bioactivity may not be easily predicted by NMR metabolomics in soft corals, or is not strongly correlated to measured diterpene levels.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 876
TI  - Assessment of sensory metabolites distribution in 3 cactus Opuntia ficus-indica fruit cultivars using UV fingerprinting and GC/MS profiling techniques
JO  - LWT
PY  - 2017
SP  - 145-154
AU  - Farag, M. A.
AU  - Maamoun, A. A.
AU  - Ehrlich, A.
AU  - Fahmy, S.
AU  - Wessjohann, L. A.
AU  - 
VL  - 80
UR  - 
DO  - 10.1016/j.lwt.2017.02.014
AB  - Among most propagated and worldwide cacti used for commercial (food) production is Opuntia ficus-indica. The present study aimed at investigating aroma compound and metabolites distribution in cactus fruits from 3 cultivars (cvs): red ‘Rose’, yellow-orange ‘Gialla’ and greenish-white ‘Bianca’ represented by both its pulp and skin samples. Two methods were applied including UV-vis fingerprinting versus gas chromatography coupled to mass spectrometry (GC-MS). Betalains predominated in red fruits, whereas carotenoids and chlorophyll were more abundant in orange and green fruits, respectively, as revealed from their crude extracts UV absorption spectra. Volatiles were profiled using headspace solid-phase micro-extraction (SPME) coupled to GC-MS. 40 Volatiles were identified with short chain aldehydes (25–32%) and acids (25–29%) as the major volatile classes. Cultivars exhibited comparable aroma profiles suggesting that volatiles cannot serve as a chemical fingerprint to distinguish between cvs. Primary metabolites mediating for fruit taste and nutritional value viz. sugars and amino acid were profiled using GC-MS post silylation with 82 identified metabolites. Glucose (62%) and fructose (16%) were found to predominate sugar composition, whereas proline was the major amino acid (3–8%). Multivariate data analyses revealed for betalain and disaccharides enrichment i.e., turanose and sucrose in fruit skin versus proline, talopyranose and lyxopyranose abundance in pulp tissue.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 875
TI  - Diazatruxenes from the Condensation Reaction of Indoles with Ninhydrin
JO  - J. Heterocyclic Chem.
PY  - 2017
SP  - 1077-1083
AU  - El-Sayed, M. T.
AU  - Wessjohann, L.
AU  - Porzel, A.
AU  - Hilgeroth, A.
AU  - 
VL  - 54
UR  - 
DO  - 10.1002/jhet.2677
AB  - The reaction of indoles with ninhydrin has been reported to provide only 1:1 condensation products (cf. A or 8) that show good antioxidant and anti‐inflammatory activity. In the present work, our synthetic challenge for the synthesis of innovative, highly substituted tetra‐indole indanes of type 1 via a 4:1 condensation reaction in acetic acid gave two unexpected new products, the diazatruxene derivatives 3 and 4. The novel structures have been characterized by their analytical and spectral data including 1D‐ and 2D‐NMR. With 5‐chloroindole, only the known 1:1 reaction.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 874
TI  - Preparation and in vitro investigations of triphenyl[ω-(tetrahydro-2H-pyran-2-yloxy)alkyl]tin(IV) compounds
JO  - Appl. Organomet. Chem.
PY  - 2017
SP  - e3630
AU  - Edeler, D.
AU  - Bensing, C.
AU  - Schmidt, H.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 31
UR  - 
DO  - 10.1002/aoc.3630
AB  - The reaction of SnPh3Li with X(CH2)nO–THP (THP = tetrahydro‐2H‐pyran‐2‐yl; n = 3, 4, 6, 8, 11; X = Cl, Br) afforded organotin(IV) compounds with the general formula Ph3Sn(CH2)nO–THP (1–5). The tetraorganotin(IV) compounds were characterized using multinuclear NMR and infrared spectroscopies and high‐resolution mass spectrometry. Anticancer activity of the synthesized compounds was tested in vitro against the A2780 (ovarian), A549 (lung), HeLa (adenocarcinoma) and SW480 (colon) tumour cell lines with SRB assay. The in vitro investigations revealed that when a shorter chain was present a higher activity was achieved; however compounds 1–5 were found to be less active than cisplatin. In addition, the most active compound, 1, enters A2780 cells and causes apoptosis by triggering both intrinsic and extrinsic caspase pathways.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 870
TI  - A Distinct Aromatic Prenyltransferase Associated with the Futalosine Pathway
JO  - ChemistrySelect
PY  - 2017
SP  - 9319-9325
AU  - Cotrim, C. A.
AU  - Weidner, A.
AU  - Strehmel, N.
AU  - Bisol, T. B.
AU  - Meyer, D.
AU  - Brandt, W.
AU  - Wessjohann, L. A.
AU  - Stubbs, M. T.
AU  - 
VL  - 2
UR  - 
DO  - 10.1002/slct.201702151
AB  - Menaquinone (MK) is an electron carrier molecule essential for respiration in most Gram positive bacteria. A crucial step in MK biosynthesis involves the prenylation of an aromatic molecule, catalyzed by integral membrane prenyltransferases of the UbiA (4‐hydroxybenzoate oligoprenyltransferase) superfamily. In the classical MK biosynthetic pathway, the prenyltransferase responsible is MenA (1,4‐dihydroxy‐2‐naphthoate octaprenyltransferase). Recently, an alternative pathway for formation of MK, the so‐called futalosine pathway, has been described in certain micro‐organisms. Until now, five soluble enzymes (MqnA‐MqnE) have been identified in the first steps. In this study, the genes annotated as ubiA from T. thermophilus and S. lividans were cloned, expressed and investigated for prenylation activity. The integral membrane proteins possess neither UbiA nor MenA activity and represent a distinct class of prenyltransferases associated with the futalosine pathway that we term MqnP. We identify a critical residue within a highly conserved Asp‐rich motif that serves to distinguish between members of the UbiA superfamily.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 864
TI  - Global proteomic analysis of advanced glycation end products in the Arabidopsis proteome provides evidence for age-related glycation hot spots
JO  - J. Biol. Chem.
PY  - 2017
SP  - 15758-15776
AU  - Bilova, T.
AU  - Paudel, G.
AU  - Shilyaev, N.
AU  - Schmidt, R.
AU  - Brauch, D.
AU  - Tarakhovskaya, E.
AU  - Milrud, S.
AU  - Smolikova, G.
AU  - Tissier, A.
AU  - Vogt, T.
AU  - Sinz, A.
AU  - Brandt, W.
AU  - Birkemeyer, C.
AU  - Wessjohann, L. A.
AU  - Frolov, A.
AU  - 
VL  - 292
UR  - 
DO  - 10.1074/jbc.M117.794537
AB  - Glycation is a post-translational modification resulting from the interaction of protein amino and guanidino groups with carbonyl compounds. Initially, amino groups react with reducing carbohydrates, yielding Amadori and Heyns compounds. Their further degradation results in formation of advanced glycation end products (AGEs), also originating from α-dicarbonyl products of monosaccharide autoxidation and primary metabolism. In mammals, AGEs are continuously formed during the life of the organism, accumulate in tissues, are well-known markers of aging, and impact age-related tissue stiffening and atherosclerotic changes. However, the role of AGEs in age-related molecular alterations in plants is still unknown. To fill this gap, we present here a comprehensive study of the age-related changes in the Arabidopsis thaliana glycated proteome, including the proteins affected and specific glycation sites therein. We also consider the qualitative and quantitative changes in glycation patterns in terms of the general metabolic background, pathways of AGE formation, and the status of plant anti-oxidative/anti-glycative defense. Although the patterns of glycated proteins were only minimally influenced by plant age, the abundance of 96 AGE sites in 71 proteins was significantly affected in an age-dependent manner and clearly indicated the existence of age-related glycation hot spots in the plant proteome. Homology modeling revealed glutamyl and aspartyl residues in close proximity (less than 5 Å) to these sites in three aging-specific and eight differentially glycated proteins, four of which were modified in catalytic domains. Thus, the sites of glycation hot spots might be defined by protein structure that indicates, at least partly, site-specific character of glycation.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 863
TI  - Identification of Phenolic Compounds from Hancornia speciosa (Apocynaceae) Leaves by UHPLC Orbitrap-HRMS
JO  - Molecules
PY  - 2017
SP  - 143
AU  - Bastos, K. X.
AU  - Dias, C. N.
AU  - Nascimento, Y. M.
AU  - da Silva, M. S.
AU  - Langassner, S. M. Z.
AU  - Wessjohann, L. A.
AU  - Tavares, J. F.
AU  - 
VL  - 22
UR  - 
DO  - 10.3390/molecules22010143
AB  - Apocynaceae is a botanical family distributed mainly in tropical and subtropical regions of the world. In Brazil, they comprise about 90 genera and 850 species, inhabiting various types of vegetation. Within this large botanical family, the genus Hancornia is considered monotypic, with its only species Hancornia speciosa Gomes. Antihypertensive, antidiabetic, and antiviral activities are described for this species. Despite having been the target of some studies, knowledge of its chemical composition is still limited. In this study, the phenolics of H. speciosa leaves were analyzed using ultra-high performance liquid chromatography (UHPLC) coupled to Orbitrap high-resolution mass spectrometry (HRMS). As a result, 14 compounds were identified viz. protocatechuic acid, catechin, and quercetin, and another 14 were putatively identified viz. B- and C-type procyanidins, while just one compound remained unknown. From the identified compounds, 17 are reported for the first time viz. coumaroylquinic acid isomers and eriodyctiol. The results show that Hancornia speciosa can serve as source of valuable phenolics.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 860
TI  - Hierarchical cluster analysis and chemical characterisation of Myrtus communis L. essential oil from Yemen region and its antimicrobial, antioxidant and anti-colorectal adenocarcinoma properties
JO  - Nat. Prod. Res.
PY  - 2017
SP  - 2158-2163
AU  - Anwar, S.
AU  - Crouch, R. A.
AU  - Awadh Ali, N. A.
AU  - Al-Fatimi, M. A.
AU  - Setzer, W. N.
AU  - Wessjohann, L.
AU  - 
VL  - 31
UR  - 
DO  - 10.1080/14786419.2016.1277346
AB  - The hydrodistilled essential oil obtained from the dried leaves of Myrtus communis, collected in Yemen, was analysed by GC–MS. Forty-one compounds were identified, representing 96.3% of the total oil. The major constituents of essential oil were oxygenated monoterpenoids (87.1%), linalool (29.1%), 1,8-cineole (18.4%), α-terpineol (10.8%), geraniol (7.3%) and linalyl acetate (7.4%). The essential oil was assessed for its antimicrobial activity using a disc diffusion assay and resulted in moderate to potent antibacterial and antifungal activities targeting mainly Bacillus subtilis, Staphylococcus aureus and Candida albicans. The oil moderately reduced the diphenylpicrylhydrazyl radical (IC50 = 4.2 μL/mL or 4.1 mg/mL). In vitro cytotoxicity evaluation against HT29 (human colonic adenocarcinoma cells) showed that the essential oil exhibited a moderate antitumor effect with IC50 of 110 ± 4 μg/mL. Hierarchical cluster analysis of M. communis has been carried out based on the chemical compositions of 99 samples reported in the literature, including Yemeni sample.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 859
TI  - Chemical Constituents of Chirita drakei
JO  - Nat. Prod. Commun.
PY  - 2017
SP  - 563-566
AU  - Anh, N. T. H.
AU  - Tuan, N. V.
AU  - Thien, D. D.
AU  - Quan, T. D.
AU  - Tam, N. T.
AU  - Lien, G. T. K.
AU  - Franke, K.
AU  - Thuy, T. T.
AU  - Sung, T. V.
AU  - 
VL  - 12
UR  - 
DO  - 10.1177/1934578X1701200425
AB  - Chirita drakei Burtt (now accepted as Primulina drakei (B.L.Burtt) Mich.Möller &amp; A.Weber) is growing on limestone mountain slopes of Ha Long Bay islands in Vietnam. The chemical investigation of the aerial parts of C. drakei led to the isolation and structural elucidation of two new compounds named chiridrakoside A (1) and chiridrakoside B (2) besides twelve known compounds comprising five phenylethanoid glycosides (3–7), two lignans (8, 9), a phenyl propanoid (10), an anthraquinone (11), a furan derivative (12) and two triterpenes (13, 14). All described compounds, except 4, 5 and 11, were obtained for the first time from the genera Chirita or Primulina. The cytotoxic activity of the isolated compounds was evaluated against the four human cancer cell lines KB (mouth epidermal carcinoma), HepG2 (hepatocellular carcinoma), Lu (lung carcinoma) and MCF7 (breast carcinoma). Epoxyconiferyl alcohol (10) exhibited cytotoxic activity against the tested cell lines (IC50 from 46 to 128 μM).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 858
TI  - Antimicrobial, Antioxidant, and Cytotoxic Activities of Ocimum forskolei and Teucrium yemense (Lamiaceae) Essential Oils
JO  - Medicines
PY  - 2017
SP  - 17
AU  - Ali, N. A. A.
AU  - Chhetri, B. K.
AU  - Dosoky, N. S.
AU  - Shari, K.
AU  - Al-Fahad, A. J. A.
AU  - Wessjohann, L.
AU  - Setzer, W. N.
AU  - 
VL  - 4
UR  - 
DO  - 10.3390/medicines4020017
AB  - Background:Ocimum forskolei and Teucrium yemense (Lamiaceae) are used in traditional medicine in Yemen. Methods: The chemical composition, antimicrobial, antioxidant and cytotoxic activities of the essential oils isolated from the leaves of Ocimum forskolei Benth. (EOOF) and two different populations of Teucrium yemense Deflers., one collected from Dhamar province (EOTY-d), and another collected from Taiz (EOTY-t) were investigated. The antimicrobial activities of the oils were evaluated against several microorganisms with the disc diffusion test or the broth microdilution test. The essential oils were screened for in-vitro cytotoxic activity against human tumor cells. EOOF and EOTY-d were screened for free-radical-inhibitory activity using the DPPH radical scavenging assay. Results: Sixty-four compounds were identified in (EOOF) representing 100% of the oil content with endo-fenchol (31.1%), fenchone (12.2%), τ-cadinol (12.2%), and methyl (E)-cinnamate (5.1%) as the major compounds. In EOTY-d, 67 compounds were identified, which made up 91% of the total oil. The most abundant constituents were (E)-caryophyllene (11.2%), α-humulene (4.0.%), γ-selinene (5.5%), 7-epi-α-selinene (20.1%), and caryophyllene oxide (20.1%), while the major compounds in EOTY-t were α-pinene (6.6%), (E)-caryophyllene (19.1%) α-humulene (6.4%), δ-cadinene (6.5%), caryophyllene oxide (4.3%), α-cadinol (9.5%), and shyobunol (4.6%). The most sensitive microorganisms for EOOF were B. subtilis, S. aureus, and C. albicans with inhibition zones of 34, 16, and 24 mm and MIC values of, 4.3 mg/mL, 4.3 mg/mL, and 8.6 mg/mL, respectively. EOTY-t showed antimicrobial activity against S. aureus, B. cereus, A. niger, and B. cinerea with MIC values of 0.156, 0.156, 0.313 and 0.313 mg/mL, respectively. Neither essential oil showed remarkable radical inhibition (IC50 = 31.55 and 31.41 μL/mL). EOTY-d was active against HT-29 human colorectal adenocarcinoma cell lines with IC50 = 43.7 μg/mL. Consistent with this, EOTY-t was active against both MCF-7 and MDA-MB-231 human breast adenocarcinoma cells. Conclusions: The antimicrobial activity of Ocimum forskolei essential oil against B. subtilis and C. albicans is consistent with its traditional use in Yemeni traditional medicine to treat skin infections. Both O. forskolei and T. yemense show wide variations in their respective essential oil compositions; there remains a need to investigate both species botanically, genetically, and phytochemically more comprehensively.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 857
TI  - Structural studies of amyloid-β peptides: Unlocking the mechanism of aggregation and the associated toxicity
JO  - Biochimie
PY  - 2017
SP  - 176-192
AU  - Aleksis, R.
AU  - Oleskovs, F.
AU  - Jaudzems, K.
AU  - Pahnke, J.
AU  - Biverstål, H.
AU  - 
VL  - 140
UR  - 
DO  - 10.1016/j.biochi.2017.07.011
AB  - Alzheimer&#39;s disease (AD) is one of the most prevalent neurodegenerative diseases worldwide. Formation of amyloid plaques consisting of amyloid-β peptides (Aβ) is one of the hallmarks of AD. Several lines of evidence have shown a correlation between the Aβ aggregation and the disease development. Extensive research has been conducted with the aim to reveal the structures of the neurotoxic Aβ aggregates. However, the exact structure of pathological aggregates and mechanism of the disease still remains elusive due to complexity of the occurring processes and instability of various disease-relevant Aβ species. In this article we review up-to-date structural knowledge about amyloid-β peptides, focusing on data acquired using solution and solid state NMR techniques. Furthermore, we discuss implications from these structural studies on the mechanisms of aggregation and neurotoxicity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 45
TI  - Natural and Nature-Inspired Macrocycles: A Chemoinformatic Overview and Relevant Examples
T2  - Practical Medicinal Chemistry with Macrocycles: Design, Synthesis, and Case Studies
PB  - 
PY  - 2017
SP  - 77-100
AU  - Wessjohann, L. A.
AU  - Bartelt, R.
AU  - Brandt, W.
AU  - 
VL  - 
UR  - 
SN  - 978-1-11909-259-9
DO  - 10.1002/9781119092599.ch4
AB  - This chapter discusses theoretical analyses and experimental studies of biologically and medicinally relevant macrocyclic compounds (MCs). The most important groups of macrocyclic natural products—excluding cyclopeptides—are discussed on the basis of selected examples. A common principle in the biosynthesis of most natural MCs is the primary synthesis of a linear precursor, followed by macrocyclization. Modification of the MC then leads to the final natural product. The chapter also focuses on the aspects of structure‐activity relationships (SAR) of macrocycles derived from chemoinformatic analyses and related theoretical methods. It further reviews the few examples that clearly show how chemoinformatics and modeling techniques, such as docking studies, can contribute essential information for drug design to improve their properties (mostly bioavailability or potency) and help to analyze and understand SAR of MCs. Finally, the chapter explores known aspects of quantitative SAR (QSAR) related to anticancer activities, antibiotics, HIV treatments, and other diseases.
A2  - Marsault, E. &amp; Peterson, M. L., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 44
TI  - Macrocycles from Multicomponent Reactions
T2  - Practical Medicinal Chemistry with Macrocycles: Design, Synthesis, and Case Studies
PB  - 
PY  - 2017
SP  - 339-376
AU  - Wessjohann, L. A.
AU  - Filho, R. A. W. N.
AU  - Puentes, A. R.
AU  - Morejón, M. C.
AU  - 
VL  - 
UR  - 
SN  - 978-1-11909-259-9
DO  - 10.1002/9781119092599.ch14
AB  - Macrocyclizations may be performed through two main processes: single‐component reactions and multicomponent reactions (MCRs). This chapter discusses MCRs and details approaches where isonitrile‐based MCRs (IMCRs) were applied to accomplish the macrocyclization of long linear molecules. It also introduces some insights about general aspects, concepts, and classifications of IMCR‐based macrocyclizations. The chapter then focuses on the early development of this method and case studies, where it was applied to the synthesis of rationally designed macrocyclic molecules. It further covers a special topic on the use of multiple IMCR‐based macrocyclizations for synthesizing three‐dimensional structures. In the past, most studies were directed toward understanding the principles of using MCRs in macrocyclizations and to explore the scope of these reactions, especially of the valuable IMCRs. In the future, this will be extended to even more and different MCRs, which in themselves are only at the advent of being explored.
A2  - Marsault, E. &amp; Peterson, M. L., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 41
TI  - Computational Studies and Biosynthesis of Natural Products with Promising Anticancer Properties
T2  - Natural Products and Cancer Drug Discovery
PB  - 
PY  - 2017
SP  - 257-285
AU  - Moumbock, A. F. A.
AU  - Simoben, C. V.
AU  - Wessjohann, L.
AU  - Sippl, W.
AU  - Günther, S.
AU  - Ntie‐Kang, F.
AU  - 
VL  - 
UR  - 
SN  - 978-953-51-3314-8
DO  - 10.5772/67650
AB  - We present an overview of computational approaches for the prediction of metabolic pathways by which plants biosynthesise compounds, with a focus on selected very promising anticancer secondary metabolites from floral sources. We also provide an overview of databases for the retrieval of useful genomic data, discussing the strengths and limitations of selected prediction software and the main computational tools (and methods), which could be employed for the investigation of the uncharted routes towards the biosynthesis of some of the identified anticancer metabolites from plant sources, eventually using specific examples to address some knowledge gaps when using these approaches.
A2  - Badria, F. A., ed.
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2545
TI  - Real-time detection of PRT1-mediated ubiquitination via fluorescently labeled substrate probes
JO  - bioRxiv
PY  - 2016
SP  - 
AU  - Mot, A. C.
AU  - Prell, E.
AU  - Klecker, M.
AU  - Naumann, C.
AU  - Faden, F.
AU  - Westermann, B.
AU  - Dissmeyer, N.
AU  - 
VL  - 
UR  - 
DO  - 10.1101/062067
AB  - The N-end rule pathway has emerged as a major system for regulating protein functions by controlling their turn-over in medical, animal and plant sciences as well as agriculture. Although novel functions and enzymes of the pathway were discovered, ubiquitination mechanism and substrate specificity of N-end rule pathway E3 Ubiquitin ligases remained elusive. Taking the first discovered bona fide plant N-end rule E3 ligase PROTEOLYSIS1 (PRT1) as a model, we use a novel tool to molecularly characterize polyubiquitination live, in real-time.We gained mechanistic insights in PRT1 substrate preference and activation by monitoring live ubiquitination by using a fluorescent chemical probe coupled to artificial substrate reporters. Ubiquitination was measured by rapid in-gel fluorescence scanning as well as in real time by fluorescence polarization.Enzymatic activity, substrate specificity, mechanisms and reaction optimization of PRT1-mediated ubiquitination were investigated ad hoc in short time and with significantly reduced reagent consumption.We demonstrated for the first time that PRT1 is indeed an E3 ligase, which was hypothesized for over two decades. These results demonstrate that PRT1 has the potential to be involved in polyubiquitination of various substrates and therefore pave the way to understanding recently discovered phenotypes of prt1 mutants.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1067
TI  - Synthesis of α-alkenyl-β-hydroxy adducts by α-addition of unprotected 4-bromocrotonic acid and amides with aldehydes and ketones by chromium(II)-mediated reactions
JO  - Appl. Organomet. Chem.
PY  - 2016
SP  - 674-679
AU  - Wessjohann, L. A.
AU  - Wild, H.
AU  - Ferreira, L. A.
AU  - Schrekker, H. S.
AU  - 
VL  - 30
UR  - 
DO  - 10.1002/aoc.3488
AB  - The regioselective and diastereoselective chromium(II)‐mediated reactions of 4‐bromocrotonic acid or amides with aldehydes and ketones can proceed without the need to protect protic sites to generate the respective α‐alkenyl‐β‐hydroxy adducts, i.e. formally the addition of the α‐anion of a carboxylic acid or amide to an oxo‐compound is featured.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1066
TI  - Applications of Convertible Isonitriles in the Ligation and Macrocyclization of Multicomponent Reaction-Derived Peptides and Depsipeptides
JO  - J. Org. Chem.
PY  - 2016
SP  - 6535-6545
AU  - Wessjohann, L. A.
AU  - Morejon, M. C.
AU  - Ojeda, G. M.
AU  - Rhoden, C. R. B.
AU  - Rivera, D. G.
AU  - 
VL  - 81
UR  - 
DO  - 10.1021/acs.joc.6b01150
AB  - Peptide ligation and macrocyclization are among the most relevant approaches in the field of peptide chemistry. Whereas a variety of strategies relying on coupling reagents and native chemical ligation are available, there is a continuous need for efficient peptide ligation and cyclization methods. Herein we report on the utilization of convertible isonitriles as effective synthetic tools for the ligation and macrocyclization of peptides arising from isocyanide-based multicomponent reactions. The strategy relies on the use of convertible isonitriles—derived from Fukuyama amines—and peptide carboxylic acids in Ugi and Passerini reactions to afford N-alkylated peptides and depsipeptides, respectively, followed by conversion of the C-terminal amide onto either N-peptidoacyl indoles or pyrroles. Such activated peptides proved efficient in the ligation to peptidic, lipidic and fluorescently labeled amines and in macrocyclization protocols. As a result, a wide set of N-substituted peptides (with methyl, glycosyl and amino acids as N-substituents), cyclic N-methylated peptides and a depsipeptide were produced in good yields using conditions that involve either classical heating or microwave irradiation. This report improves the repertoire of peptide covalent modification methods by exploiting the synthetic potential of multicomponent reactions and convertible isonitriles.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1063
TI  - The Vacuolar Proton-Cation Exchanger EcNHX1 Generates pH Signals for the Expression of Secondary Metabolism in Eschscholzia californica
JO  - Plant Physiol.
PY  - 2016
SP  - 1135-1148
AU  - Weigl, S.
AU  - Brandt, W.
AU  - Langhammer, R.
AU  - Roos, W.
AU  - 
VL  - 170
UR  - 
DO  - 10.1104/pp.15.01570
AB  - Cell cultures of Eschscholzia californica react to a fungal elicitor by the overproduction of antimicrobial benzophenanthridine alkaloids. The signal cascade toward the expression of biosynthetic enzymes includes (1) the activation of phospholipase A2 at the plasma membrane, resulting in a peak of lysophosphatidylcholine, and (2) a subsequent, transient efflux of vacuolar protons, resulting in a peak of cytosolic H+. This study demonstrates that one of the Na+/H+ antiporters acting at the tonoplast of E. californica cells mediates this proton flux. Four antiporter-encoding genes were isolated and cloned from complementary DNA (EcNHX1–EcNHX4). RNA interference-based, simultaneous silencing of EcNHX1, EcNHX3, and EcNHX4 resulted in stable cell lines with largely diminished capacities of (1) sodium-dependent efflux of vacuolar protons and (2) elicitor-triggered overproduction of alkaloids. Each of the four EcNHX genes of E. californica reconstituted the lack of Na+-dependent H+ efflux in a Δnhx null mutant of Saccharomyces cerevisiae. Only the yeast strain transformed with and expressing the EcNHX1 gene displayed Na+-dependent proton fluxes that were stimulated by lysophosphatidylcholine, thus giving rise to a net efflux of vacuolar H+. This finding was supported by three-dimensional protein homology models that predict a plausible recognition site for lysophosphatidylcholine only in EcNHX1. We conclude that the EcNHX1 antiporter functions in the elicitor-initiated expression of alkaloid biosynthetic genes by recruiting the vacuolar proton pool for the signaling process.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1055
TI  - Discovering Regulated Metabolite Families in Untargeted Metabolomics Studies
JO  - Anal. Chem.
PY  - 2016
SP  - 8082-8090
AU  - Treutler, H.
AU  - Tsugawa, H.
AU  - Porzel, A.
AU  - Gorzolka, K.
AU  - Tissier, A.
AU  - Neumann, S.
AU  - Balcke, G. U.
AU  - 
VL  - 88
UR  - 
DO  - 10.1021/acs.analchem.6b01569
AB  - The identification of metabolites by mass spectrometry constitutes a major bottleneck which considerably limits the throughput of metabolomics studies in biomedical or plant research. Here, we present a novel approach to analyze metabolomics data from untargeted, data-independent LC-MS/MS measurements. By integrated analysis of MS1 abundances and MS/MS spectra, the identification of regulated metabolite families is achieved. This approach offers a global view on metabolic regulation in comparative metabolomics. We implemented our approach in the web application “MetFamily”, which is freely available at http://msbi.ipb-halle.de/MetFamily/. MetFamily provides a dynamic link between the patterns based on MS1-signal intensity and the corresponding structural similarity at the MS/MS level. Structurally related metabolites are annotated as metabolite families based on a hierarchical cluster analysis of measured MS/MS spectra. Joint examination with principal component analysis of MS1 patterns, where this annotation is preserved in the loadings, facilitates the interpretation of comparative metabolomics data at the level of metabolite families. As a proof of concept, we identified two trichome-specific metabolite families from wild-type tomato Solanum habrochaites LA1777 in a fully unsupervised manner and validated our findings based on earlier publications and with NMR.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1052
TI  - Spin-labelled diketopiperazines and peptide–peptoid chimera by Ugi-multi-component-reactions
JO  - Org. Biomol. Chem.
PY  - 2016
SP  - 11336-11341
AU  - Sultani, H. N.
AU  - Haeri, H. H.
AU  - Hinderberger, D.
AU  - Westermann, B.
AU  - 
VL  - 14
UR  - 
DO  - 10.1039/C6OB02194H
AB  - For the first time, spin-labelled coumpounds have been obtained by isonitrile-based multi component reactions (IMCRs). The typical IMCR Ugi-protocols offer a simple experimental setup allowing structural variety by which labelled diketopiperazines (DKPs) and peptide–peptoid chimera have been synthesized. The reaction keeps the paramagnetic spin label intact and offers a simple and versatile route to a large variety of new and chemically diverse spin labels.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1050
TI  - Revisiting rodent models: Octodon degus as Alzheimer’s disease model?
JO  - Acta Neuropathol. Commun.
PY  - 2016
SP  - 91
AU  - Steffen, J.
AU  - Krohn, M.
AU  - Paarmann, K.
AU  - Schwitlick, C.
AU  - Brüning, T.
AU  - Marreiros, R.
AU  - Müller-Schiffmann, A.
AU  - Korth, C.
AU  - Braun, K.
AU  - Pahnke, J.
AU  - 
VL  - 4
UR  - 
DO  - 10.1186/s40478-016-0363-y
AB  - Alzheimer’s disease primarily occurs as sporadic disease and is accompanied with vast socio-economic problems. The mandatory basic research relies on robust and reliable disease models to overcome increasing incidence and emerging social challenges. Rodent models are most efficient, versatile, and predominantly used in research. However, only highly artificial and mostly genetically modified models are available. As these ‘engineered’ models reproduce only isolated features, researchers demand more suitable models of sporadic neurodegenerative diseases. One very promising animal model was the South American rodent Octodon degus, which was repeatedly described as natural ‘sporadic Alzheimer’s disease model’ with ‘Alzheimer’s disease-like neuropathology’. To unveil advantages over the ‘artificial’ mouse models, we re-evaluated the age-dependent, neurohistological changes in young and aged Octodon degus (1 to 5-years-old) bred in a wild-type colony in Germany. In our hands, extensive neuropathological analyses of young and aged animals revealed normal age-related cortical changes without obvious signs for extensive degeneration as seen in patients with dementia. Neither significant neuronal loss nor enhanced microglial activation were observed in aged animals. Silver impregnation methods, conventional, and immunohistological stains as well as biochemical fractionations revealed neither amyloid accumulation nor tangle formation. Phosphoepitope-specific antibodies against tau species displayed similar intraneuronal reactivity in both, young and aged Octodon degus.In contrast to previous results, our study suggests that Octodon degus born and bred in captivity do not inevitably develop cortical amyloidosis, tangle formation or neuronal loss as seen in Alzheimer’s disease patients or transgenic disease models.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1048
TI  - Expeditious Entry to Functionalized Pseudo-peptidic Organoselenide Redox Modulators via Sequential Ugi/SN Methodology
JO  - Anti-Cancer Agents Med. Chem.
PY  - 2016
SP  - 621-632
AU  - Shaaban, S.
AU  - Negm, A.
AU  - Sobh, M. A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 16
UR  - 
DO  - 10.2174/1871520615666150916092035
AB  - An efficient route towards the synthesis of symmetrical diselenide and seleniumcontaining quinone pseudopeptides via one-pot Ugi and sequential nucleophilic substitution (SN) methodology was developed. Compounds were evaluated for their antimicrobial and anticancer activities and their corresponding antioxidant/pro-oxidant profiles were assesed employing 2,2-diphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like activity assays. Selenium based quinones were among the most potent cytotoxic compounds with a slight preference for MCF-7 compared to HepG2 cells and good free radical scavenging activity. Furthermore, symmetrical diselenides exhibited the most potent GPx-like activity compared to ebselen. Moreover, compounds 7, 8, 9 and 10 exhibited similar antifungal activity to the antifungal drug clotrimazole with modest activity against the Gram-positive bacterium S. aureus. These results indicate that some of the synthesized organoselenides are redox modulating agent with promising anti-cancer and antifungal potentials.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1047
TI  - Combinatorial synthesis, in silico, molecular and biochemical studies of tetrazole-derived organic selenides with increased selectivity against hepatocellular carcinoma
JO  - Eur. J. Med. Chem.
PY  - 2016
SP  - 55-71
AU  - Shaaban, S.
AU  - Negm, A.
AU  - Ashmawy, A. M.
AU  - Ahmed, D. M.
AU  - Wessjohann, L. A.
AU  - 
VL  - 122
UR  - 
DO  - 10.1016/j.ejmech.2016.06.005
AB  - Novel tetrazole-based diselenides and selenoquinones were synthesized via azido-Ugi and sequential nucleophilic substitution (SN) strategy. Molecular docking study into mammalian TrxR1 was used to predict the anticancer potential of the newly synthesized compounds. The cytotoxic activity of the compounds was evaluated using hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cancer cells and compared with their cytotoxicity in normal fibroblast (WI-38) cells. The corresponding redox properties of the synthesized compounds were assessed employing 2,2-diphenyl-1-picrylhydrazyl (DPPH), glutathione peroxidase (GPx)-like activity and bleomycin dependent DNA damage. In general, diselenides showed preferential cytotoxicity to HepG2 compared to MCF-7 cells. These compounds exhibited also good GPx catalytic activity compared to ebselen (up to 5 fold). Selenoquinones 18, 21, 22 and 23 were selected to monitor the expression levels of caspase-8, Bcl-2 and Ki-67 molecular biomarkers. Interestingly, these compounds downregulated the Bcl-2 and Ki-67 expression levels and activated the expression of caspase-8 in HepG2 cells compared to untreated cells. These results indicate that some of the newly synthesized compounds possess anti-HepG2 activity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1044
TI  - Negative ion electrospray high-resolution tandem mass spectrometry of polyphenols
JO  - J. Mass Spectrom.
PY  - 2016
SP  - 33-43
AU  - Schmidt, J.
AU  - 
VL  - 51
UR  - 
DO  - 10.1002/jms.3712
AB  - Representative compounds with a 1,3‐dihydroxybenzene substructure belonging to different important polyphenol classes (stilbenes, flavones, isoflavones, flavonols, flavanones, flavanols, phloroglucinols, anthraquinones and bisanthraquinones) were investigated based on detailed high‐resolution tandem mass spectrometry measurements with an Orbitrap system under negative ion electrospray conditions. The mass spectral behaviour of these compound classes was compared among each other not only with respect to previously described losses of CO, CH2CO and C3O2 but also concerning the loss of CO2 and successive specific fragmentations. Furthermore, some unusual fragmentations such as the loss of a methyl radical during mass spectral decomposition are discussed. The obtained results demonstrate both similarities and differences in their mass spectral fragmentation under MSn conditions, allowing a characterization of the corresponding compound type.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1027
TI  - Activity Regulation by Heteromerization of Arabidopsis Allene Oxide Cyclase Family Members
JO  - Plants
PY  - 2016
SP  - 3
AU  - Otto, M.
AU  - Naumann, C.
AU  - Brandt, W.
AU  - Wasternack, C.
AU  - Hause, B.
AU  - 
VL  - 5
UR  - 
DO  - 10.3390/plants5010003
AB  - Jasmonates (JAs) are lipid-derived signals in plant stress responses and development. A crucial step in JA biosynthesis is catalyzed by allene oxide cyclase (AOC). Four genes encoding functional AOCs (AOC1, AOC2, AOC3 and AOC4) have been characterized for Arabidopsis thaliana in terms of organ- and tissue-specific expression, mutant phenotypes, promoter activities and initial in vivo protein interaction studies suggesting functional redundancy and diversification, including first hints at enzyme activity control by protein-protein interaction. Here, these analyses were extended by detailed analysis of recombinant proteins produced in Escherichia coli. Treatment of purified AOC2 with SDS at different temperatures, chemical cross-linking experiments and protein structure analysis by molecular modelling approaches were performed. Several salt bridges between monomers and a hydrophobic core within the AOC2 trimer were identified and functionally proven by site-directed mutagenesis. The data obtained showed that AOC2 acts as a trimer. Finally, AOC activity was determined in heteromers formed by pairwise combinations of the four AOC isoforms. The highest activities were found for heteromers containing AOC4 + AOC1 and AOC4 + AOC2, respectively. All data are in line with an enzyme activity control of all four AOCs by heteromerization, thereby supporting a putative fine-tuning in JA formation by various regulatory principles.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry; Molecular Signal Processing
ER  - 


TY  - JOUR
ID  - 1025
TI  - Solution- and Solid-Phase Macrocyclization of Peptides by the Ugi–Smiles Multicomponent Reaction: Synthesis of N-Aryl-Bridged Cyclic Lipopeptides
JO  - Org. Lett.
PY  - 2016
SP  - 4096-4099
AU  - Morejon, M. C.
AU  - Laub, A.
AU  - Westermann, B.
AU  - Rivera, D. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 18
UR  - 
DO  - 10.1021/acs.orglett.6b02001
AB  - A new multicomponent methodology for the solution- and solid-phase macrocyclization of peptides is described. The approach comprises the utilization of the Ugi–Smiles reaction for the cyclization of 3-nitrotyrosine-containing peptides either by the N-terminus or the lysine side-chain amino groups. Both the on-resin and solution cyclizations took place with good to excellent efficiency in the presence of an aldehyde and a lipidic isocyanide, while the use of paraformaldehyde required an aminocatalysis-mediated imine formation prior to the on-resin Ugi–Smiles ring closure. The introduction of a turn motif in the peptide sequence facilitated the cyclization step, shortened the reaction time, and delivered crude products with &gt;90% purity. This powerful method provided a variety of structurally novel N-aryl-bridged cyclic lipopeptides occurring as single atropisomers
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1023
TI  - Passerini Reactions on Biocatalytically Derived Chiral Azetidines
JO  - Molecules
PY  - 2016
SP  - 1153
AU  - Moni, L.
AU  - Banfi, L.
AU  - Basso, A.
AU  - Bozzano, A.
AU  - Spallarossa, M.
AU  - Wessjohann, L.
AU  - Riva, R.
AU  - 
VL  - 21
UR  - 
DO  - 10.3390/molecules21091153
AB  - The purpose of this study was to explore a series of Passerini reactions on a biocatalytically derived enantiopure azetidine-2-carboxyaldehyde in order to obtain, in a diastereoselective manner, polyfunctionalised derivatives having the potential to be cyclized to chiral bridged bicyclic nitrogen heterocycles. While diastereoselectivity was poor under classical Passerini conditions, a significant increase of diastereoselectivity (up to 76:24) was gained by the use of zinc bromide as promoter. The methodology has a broad scope and yields are always good.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1020
TI  - Chronic Toxoplasma gondii infection enhances β-amyloid phagocytosis and clearance by recruited monocytes
JO  - Acta Neuropathol. Commun.
PY  - 2016
SP  - 25
AU  - Möhle, L.
AU  - Israel, N.
AU  - Paarmann, K.
AU  - Krohn, M.
AU  - Pietkiewicz, S.
AU  - Müller, A.
AU  - Lavrik, I. N.
AU  - Buguliskis, J. S.
AU  - Schott, B. H.
AU  - Schlüter, D.
AU  - Gundelfinger, E. D.
AU  - Montag, D.
AU  - Seifert, U.
AU  - Pahnke, J.
AU  - Dunay, I. R.
AU  - 
VL  - 4
UR  - 
DO  - 10.1186/s40478-016-0293-8
AB  - IntroductionAlzheimer’s disease (AD) is associated with the accumulation of β-amyloid (Aβ) as senile plaques in the brain, thus leading to neurodegeneration and cognitive impairment. Plaque formation depends not merely on the amount of generated Aβ peptides, but more importantly on their effective removal. Chronic infections with neurotropic pathogens, most prominently the parasite Toxoplasma (T.) gondii, are frequent in the elderly, and it has been suggested that the resulting neuroinflammation may influence the course of AD. In the present study, we investigated how chronic T. gondii infection and resulting neuroinflammation affect plaque deposition and removal in a mouse model of AD.ResultsChronic infection with T. gondii was associated with reduced Aβ and plaque load in 5xFAD mice. Upon infection, myeloid-derived CCR2hi Ly6Chi monocytes, CCR2+ Ly6Cint, and CCR2+ Ly6Clow mononuclear cells were recruited to the brain of mice. Compared to microglia, these recruited mononuclear cells showed highly increased phagocytic capacity of Aβ ex vivo. The F4/80+ Ly6Clow macrophages expressed high levels of Triggering Receptor Expressed on Myeloid cells 2 (TREM2), CD36, and Scavenger Receptor A1 (SCARA1), indicating phagocytic activity. Importantly, selective ablation of CCR2+ Ly6Chi monocytes resulted in an increased amount of Aβ in infected mice. Elevated insulin-degrading enzyme (IDE), matrix metalloproteinase 9 (MMP9), as well as immunoproteasome subunits β1i/LMP2, β2i/MECL-1, and β5i/LMP7 mRNA levels in the infected brains indicated increased proteolytic Aβ degradation. Particularly, LMP7 was highly expressed by the recruited mononuclear cells in the brain, suggesting a novel mechanism of Aβ clearance.ConclusionsOur results indicate that chronic Toxoplasma infection ameliorates β-amyloidosis in a murine model of AD by activation of the immune system, specifically by recruitment of Ly6Chi monocytes and by enhancement of phagocytosis and degradation of soluble Aβ. Our findings provide evidence for a modulatory role of inflammation-induced Aβ phagocytosis and degradation by newly recruited peripheral immune cells in the pathophysiology of AD.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1019
TI  - Biological Potential of Halfsandwich Ruthenium(II) and Iridium (III) Complexes
JO  - Anti-Cancer Agents Med. Chem.
PY  - 2016
SP  - 1455-1460
AU  - Ludwig, G.
AU  - Mojić, M.
AU  - Bulatović, M.
AU  - Mijatović, S.
AU  - Maksimović-Ivanić, D.
AU  - Steinborn, D.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 16
UR  - 
DO  - 10.2174/1871520615666151029100749
AB  - In vitro studies with the ruthenium(II) and analogous iridium(III) complexes [Ru(η6- p-cymene)Cl2{Ph2PCH2CH2CH2S(O)xPh-κP}], [Ru(η6-p-cymene)Cl{Ph2PCH2CH2CH2S(O)xPh- κP,κS}][PF6] (1–4), [Ir(η5-C5Me5)Cl2{Ph2PCH2CH2CH2S(O)xPh-κP}] and [Ir(η5-C5Me5)Cl{Ph2 PCH2CH2CH2S(O)xPh-κP,κS}][PF6] (5–8; x = 0, 1) revealed the high selectivity toward the 8505C, A253, MCF-7, SW480 and 518A2 cancer cell lines. Thus, the cationic ruthenium complex 4 proved to be the most selective one. In case of the neutral and cationic ruthenium complexes 1–4 the caspase-dependent apoptotic cell death was proven as the main cause of the drug’s tumoricidal action on 8505C cell line.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1015
TI  - Redox proteomics: Methods for the identification and enrichment of redox-modified proteins and their applications
JO  - Proteomics
PY  - 2016
SP  - 197-213
AU  - Lennicke, C.
AU  - Rahn, J.
AU  - Heimer, N.
AU  - Lichtenfels, R.
AU  - Wessjohann, L. A.
AU  - Seliger, B.
AU  - 
VL  - 16
UR  - 
DO  - 10.1002/pmic.201500268
AB  - PTMs are defined as covalent additions to functional groups of amino acid residues in proteins like phosphorylation, glycosylation, S‐nitrosylation, acetylation, methylation, lipidation, SUMOylation as well as oxidation. Oxidation of proteins has been characterized as a double‐edged sword. While oxidative modifications, in particular of cysteine residues, are widely involved in the regulation of cellular homeostasis, oxidative stress resulting in the oxidation of biomolecules along with the disruption of their biological functions can be associated with the development of diseases, such as cancer, diabetes, and neurodegenerative diseases, respectively. This is also the case for advanced glycation end products, which result from chemical reactions of keto compounds such as oxidized sugars with proteins. The role of oxidative modifications under physiological and pathophysiological conditions remains largely unknown. Recently, novel technologies have been established that allow the enrichment, identification, and characterization of specific oxidative PTMs (oxPTMs). This is essential to develop strategies to prevent and treat diseases that are associated with oxidative stress. Therefore this review will focus on (i) the methods and technologies, which are currently applied for the detection, identification, and quantification of oxPTMs including the design of high throughput approaches and (ii) the analyses of oxPTMs related to physiological and pathological conditions.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1014
TI  - Versatile antitumor potential of isoxanthohumol: Enhancement of paclitaxel activity in vivo
JO  - Pharmacol. Res.
PY  - 2016
SP  - 62-73
AU  - Krajnović, T.
AU  - Kaluđerović, G. N.
AU  - Wessjohann, L. A.
AU  - Mijatović, S.
AU  - Maksimović-Ivanić, D.
AU  - 
VL  - 105
UR  - 
DO  - 10.1016/j.phrs.2016.01.011
AB  - Isoxanthohumol (IXN), a prenylated flavonoid from hops, exhibits diverse biological activities, e.g. antitumor, antiinflammatory, antioxidant and antiangiogenic. In this study, the effect of IXN is evaluated on two melanoma cell lines with dissimilar molecular background, B16 and A375. The treatment of both cell lines with IXN resulted in dose-dependent decrease of cell viability. Abolished viability was in correlation with changed morphology and loss of dividing potential indicating phenotypical alteration of both tested cell lines. While modified B16 cells underwent the process of non-classic differentiation followed by tyrosinase activity without enhancement of melanin content, inhibition of Notch 1, β-catenin and Oct-3/4 was observed in A375 cells indicating loss of their pluripotent characteristics. In parallel with this, distinct subpopulations in both cell cultures entered the process of programmed cell death—apoptosis in a caspase independent manner. The described changes in cultures upon exposure to IXN could be connected with the suppression of reactive oxygen (ROS) and nitrogen species (RNS) induced by the drug. Despite the differences in which IXN promoted modifications in the upper part of the PI3K/Akt and MEK-ERK signaling pathways between B16 and A375 cells, p70S6K and its target S6 protein in both types of melanoma cells, after transient activation, became inhibited. In addition to direct input of IXN on cell viability, this study for the first time shows that IXN strongly sensitizes melanoma cells to the treatment with paclitaxel in vivo, in concordance with data obtained in vitro on B16 cells as well as their highly invasive F10 subclone.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1013
TI  - The RADAR Project—A Service for Research Data Archival and Publication
JO  - ISPRS Int. J. Geo-Inf.
PY  - 2016
SP  - 28
AU  - Kraft, A.
AU  - Razum, M.
AU  - Potthoff, J.
AU  - Porzel, A.
AU  - Engel, T.
AU  - Lange, F.
AU  - Van den Broek, K.
AU  - Furtado, F.
AU  - 
VL  - 5
UR  - 
DO  - 10.3390/ijgi5030028
AB  - The aim of the RADAR (Research Data Repository) project is to set up and establish an infrastructure that facilitates research data management: the infrastructure will allow researchers to store, manage, annotate, cite, curate, search and find scientific data in a digital platform available at any time that can be used by multiple (specialized) disciplines. While appropriate and innovative preservation strategies and systems are in place for the big data communities (e.g., environmental sciences, space, and climate), the stewardship for many other disciplines, often called the “long tail research domains”, is uncertain. Funded by the German Research Foundation (DFG), the RADAR collaboration project develops a service oriented infrastructure for the preservation, publication and traceability of (independent) research data. The key aspect of RADAR is the implementation of a two-stage business model for data preservation and publication: clients may preserve research results for up to 15 years and assign well-graded access rights, or to publish data with a DOI assignment for an unlimited period of time. Potential clients include libraries, research institutions, publishers and open platforms that desire an adaptable digital infrastructure to archive and publish data according to their institutional requirements and workflows.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1012
TI  - Archivierung und Publikation von Forschungsdaten: Die Rolle von digitalen Repositorien am Beispiel des RADAR-Projekts
JO  - Bibliotheksdienst
PY  - 2016
SP  - 623-635
AU  - Kraft, A.
AU  - Razum, M.
AU  - Potthoff, J.
AU  - Porzel, A.
AU  - Engel, T.
AU  - Lange, F.
AU  - Van den Broek, K.
AU  - 
VL  - 50
UR  - 
DO  - 10.1515/bd-2016-0077
AB  - The goal of RADAR is to simplify and establish inter-disciplinary research data management for university libraries and projects. In summer 2016‚ ‘RADAR – Research Data Repository‘ starts as a service that offers researchers, institutions of different disciplines and publishers a generic infrastructure for archiving and publishing their research data. Among others, services are long-term data availability with Handle or Digital Object Identifier (DOI), an adaptable role and access rights management, an optional peer review function and access statistics. The business model encourages researchers to integrate arising charges for using the repository into applications for Third-Party funding and data management plans. Published data are available as Open Data to be used by Data Mining, metadata harvesting or linking with search portals. This interlinking enables a sustainable research data management and the establishment of data infrastructures like RADAR.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1009
TI  - Palladium(II) complexes with R2edda-derived ligands
JO  - J. Coord. Chem.
PY  - 2016
SP  - 1337-1345
AU  - Kaluđerović, G. N.
AU  - Hernández-Corroto, E.
AU  - Brandt, W.
AU  - Zmejkovski, B. B.
AU  - Gómez-Ruiz, S.
AU  - 
VL  - 69
UR  - 
DO  - 10.1080/00958972.2016.1168519
AB  - Four palladium(II) complexes with R2edda ligands, dichlorido(O,O′-dialkylethylenediamine-N,N′-diacetate)palladium(II) monohydrates, [PdCl2(R2edda)]∙H2O, R = Me, Et, n-Pr, i-Bu, and the new ligand precursor i-Bu2edda∙2HCl∙H2O, O,O′-diisobutylethylenediamine-N,N′-diacetate dihydrochloride monohydrate, were synthesized and characterized by IR, 1H and 13C NMR spectroscopy, and elemental analysis. DFT calculations were performed for the palladium(II) complexes and a high possibility for isomer formation due to stereogenic N ligand atoms was confirmed. Moreover, DFT simulations revealed energetic profile of isomer formation. Computational outcomes are in agreement with spectroscopic instrumental findings, both strongly indicating a non-stereoselective reaction between selected esters and K2[PdCl4], forming isomers.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1007
TI  - Sideritis spp. Extracts Enhance Memory and Learning in Alzheimer’s β-Amyloidosis Mouse Models and Aged C57Bl/6 Mice
JO  - J. Alzheimers Dis.
PY  - 2016
SP  - 967-980
AU  - Hofrichter, J.
AU  - Krohn, M.
AU  - Schumacher, T.
AU  - Lange, C.
AU  - Feistel, B.
AU  - Walbroel, B.
AU  - Pahnke, J.
AU  - 
VL  - 53
UR  - 
DO  - 10.3233/JAD-160301
AB  - Nowadays, Alzheimer’s disease is the most prevalent epiphenomenon of the aging population. Although soluble amyloid-β (Aβ) species (monomers, oligomers) are recognized triggers of the disease, no therapeutic approach is able to stop it. Herbal medicines are used to treat different diseases in many regions of the world. On the Balkan Peninsula, at the eastern Mediterranean Sea, and adjacent regions, Sideritis species are used as traditional medicine to prevent age-related problems in elderly. To evaluate this traditional knowledge in controlled experiments, we tested extracts of two commonly used Sideritis species, Sideritis euboea and Sideritis scardica, with regard to their effects on cognition in APP-transgenic and aged, non-transgenic C57Bl/6 mice. Additionally, histomorphological and biochemical changes associated with Aβ deposition and treatment were assessed. We found that daily oral treatment with Sideritis spp. extracts highly enhanced cognition in aged, non-transgenic as well as in APP-transgenic mice, an effect that was even more pronounced when extracts of both species were applied in combination. The treatment strongly reduced Aβ42 load in APP-transgenic mice, accompanied by increased phagocytic activity of microglia, and increased expression of the α-secretase ADAM10. Moreover, the treatment was able to fully rescue neuronal loss of APP-transgenic mice to normal levels as seen in non-transgenic controls. Having the traditional knowledge in mind, our results imply that treatment with Sideritis spp. extracts might be a potent, well-tolerated option for treating symptoms of cognitive impairment in elderly and with regard to Alzheimer’s disease by affecting its most prominent hallmarks: Aβ pathology and cognitive decline.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1003
TI  - Natural Products from Microalgae with Potential against Alzheimer’s Disease: Sulfolipids Are Potent Glutaminyl Cyclase Inhibitors
JO  - Mar. Drugs
PY  - 2016
SP  - 203
AU  - Hielscher-Michael, S.
AU  - Griehl, C.
AU  - Buchholz, M.
AU  - Demuth, H.-U.
AU  - Arnold, N.
AU  - Wessjohann, L. A.
AU  - 
VL  - 14
UR  - 
DO  - 10.3390/md14110203
AB  - In recent years, many new enzymes, like glutaminyl cyclase (QC), could be associated with pathophysiological processes and represent targets for many diseases, so that enzyme-inhibiting properties of natural substances are becoming increasingly important. In different studies, the pathophysiology connection of QC to various diseases including Alzheimer’s disease (AD) was described. Algae are known for the ability to synthesize complex and highly-diverse compounds with specific enzyme inhibition properties. Therefore, we screened different algae species for the presence of QC inhibiting metabolites using a new “Reverse Metabolomics” technique including an Activity-correlation Analysis (AcorA), which is based on the correlation of bioactivities to mass spectral data with the aid of mathematic informatics deconvolution. Thus, three QC inhibiting compounds from microalgae belonging to the family of sulfolipids were identified. The compounds showed a QC inhibition of 81% and 76% at concentrations of 0.25 mg/mL and 0.025 mg/mL, respectively. Thus, for the first time, sulfolipids are identified as QC inhibiting compounds and possess substructures with the required pharmacophore qualities. They represent a new lead structure for QC inhibitors.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 999
TI  - Site-specific analysis of advanced glycation end products in plasma proteins of type 2 diabetes mellitus patients
JO  - Anal. Bioanal. Chem.
PY  - 2016
SP  - 5557-5566
AU  - Greifenhagen, U.
AU  - Frolov, A.
AU  - Blüher, M.
AU  - Hoffmann, R.
AU  - 
VL  - 408
UR  - 
DO  - 10.1007/s00216-016-9651-4
AB  - Advanced glycation end products (AGEs) are posttranslational modifications formed non-enzymatically from the reaction of carbohydrates and their degradation products with proteins. Accumulation of AGEs is associated with the progression of severe diabetic complications, for example, and elevated tissue levels of AGEs might even predict these pathologies. As AGE formation is often site-specific, mapping of these modification sites may reveal more sensitive and specific markers than the global tissue level. Here, 42 AGE modifications were identified in a bottom-up proteomic approach by tandem mass spectrometry, which corresponded to 36 sites in 22 high to medium abundant proteins in individual plasma samples obtained from type 2 diabetes mellitus (T2DM) patients with long disease duration (&gt;10 years). Major modifications were glarg (11 modification sites) and carboxymethylation (5) of arginine and formylation (8), acetylation (7), and carboxymethylation (7) of lysine residues. Relative quantification of these sites in plasma samples obtained from normoglycemic individuals (n = 47) and patients with T2DM being newly diagnosed (n = 47) or of medium (2–5 years, n = 20) and long disease duration (&gt;10 years, n = 20) did not reveal any significant differences.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 998
TI  - Immobilized metal affinity chromatography on collapsed Langmuir-Blodgett iron(III) stearate films and iron(III) oxide nanoparticles for bottom-up phosphoproteomics
JO  - J. Chromatogr. A
PY  - 2016
SP  - 181-190
AU  - Gladilovich, V.
AU  - Greifenhagen, U.
AU  - Sukhodolov, N.
AU  - Selyutin, A.
AU  - Singer, D.
AU  - Thieme, D.
AU  - Majovsky, P.
AU  - Shirkin, A.
AU  - Hoehenwarter, W.
AU  - Bonitenko, E.
AU  - Podolskaya, E.
AU  - Frolov, A.
AU  - 
VL  - 1443
UR  - 
DO  - 10.1016/j.chroma.2016.03.044
AB  - Phosphorylation is the enzymatic reaction of site-specific phosphate transfer from energy-rich donors to the side chains of serine, threonine, tyrosine, and histidine residues in proteins. In living cells, reversible phosphorylation underlies a universal mechanism of intracellular signal transduction. In this context, analysis of the phosphoproteome is a prerequisite to better understand the cellular regulatory networks. Conventionally, due to the low contents of signaling proteins, selective enrichment of proteolytic phosphopeptides by immobilized metal affinity chromatography (IMAC) is performed prior to their LC–MS or -MS/MS analysis. Unfortunately, this technique still suffers from low selectivity and compromised analyte recoveries. To overcome these limitations, we propose IMAC systems comprising stationary phases based on collapsed Langmuir-Blodgett films of iron(III) stearate (FF) or iron(III) oxide nanoparticles (FO) and mobile phases relying on ammonia, piperidine and heptadecafluorooctanesulfonic acid (PFOS). Experiments with model phosphopeptides and phosphoprotein tryptic digests showed superior binding capacity, selectivity and recovery for both systems in comparison to the existing commercial analogs. As evidenced by LC–MS/MS analysis of the HeLa phosphoproteome, these features of the phases resulted in increased phosphoproteome coverage in comparison to the analogous commercially available phases, indicating that our IMAC protocol is a promising chromatographic tool for in-depth phosphoproteomic research.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 993
TI  - Activation of Mitochondrial Complex II-Dependent Respiration Is Beneficial for α-Synucleinopathies
JO  - Mol. Neurobiol.
PY  - 2016
SP  - 4728-4744
AU  - Fröhlich, C.
AU  - Zschiebsch, K.
AU  - Gröger, V.
AU  - Paarmann, K.
AU  - Steffen, J.
AU  - Thurm, C.
AU  - Schropp, E.-M.
AU  - Brüning, T.
AU  - Gellerich, F.
AU  - Radloff, M.
AU  - Schwabe, R.
AU  - Lachmann, I.
AU  - Krohn, M.
AU  - Ibrahim, S.
AU  - Pahnke, J.
AU  - 
VL  - 53
UR  - 
DO  - 10.1007/s12035-015-9399-4
AB  - Parkinson’s disease and dementia with Lewy bodies are major challenges in research and clinical medicine world-wide and contribute to the most common neurodegenerative disorders. Previously, specific mitochondrial polymorphisms have been found to enhance clearance of amyloid-β from the brain of APP-transgenic mice leading to beneficial clinical outcome. It has been discussed whether specific mitochondrial alterations contribute to disease progression or even prevent toxic peptide deposition, as seen in many neurodegenerative diseases. Here, we investigated α-synuclein-transgenic C57BL/6J mice with the A30P mutation, and a novel A30P C57BL/6J mouse model with three mitochondrial DNA polymorphisms in the ND3, COX3 and mtRNAArg genes, as found in the inbred NOD/LtJ mouse strain. We were able to detect that the new model has increased mitochondrial complex II-respiration which occurs in parallel to neuronal loss and improved motor performance, although it exhibits higher amounts of high molecular weight species of α-synuclein. High molecular weight aggregates of different peptides are controversially discussed in the light of neurodegeneration. A favourable hypothesis states that high molecular weight species are protective and of minor importance for the pathogenesis of neurodegenerative disorders as compared to the extreme neurotoxic monomers and oligomers. Summarising, our results point to a potentially protective and beneficial effect of specific mitochondrial polymorphisms which cause improved mitochondrial complex II-respiration in α-synucleinopathies, an effect that could be exploited further for pharmaceutical interventions.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 992
TI  - Tricyclic Acylphloroglucinols from Hypericum lanceolatum and Regioselective Synthesis of Selancins A and B
JO  - J. Nat. Prod.
PY  - 2016
SP  - 743-753
AU  - Fobofou, S. A. T.
AU  - Franke, K.
AU  - Porzel, A.
AU  - Brandt, W.
AU  - Wessjohann, L. A.
AU  - 
VL  - 79
UR  - 
DO  - 10.1021/acs.jnatprod.5b00673
AB  - The chemical investigation of the chloroform extract of Hypericum lanceolatum guided by 1H NMR, ESIMS, and TLC profiles led to the isolation of 11 new tricyclic acylphloroglucinol derivatives, named selancins A–I (1–9) and hyperselancins A and B (10 and 11), along with the known compound 3-O-geranylemodin (12), which is described for a Hypericum species for the first time. Compounds 8 and 9 are the first examples of natural products with a 6-acyl-2,2-dimethylchroman-4-one core fused with a dimethylpyran unit. The new compounds 1–9 are rare acylphloroglucinol derivatives with two fused dimethylpyran units. Compounds 10 and 11 are derivatives of polycyclic polyprenylated acylphloroglucinols related to hyperforin, the active component of St. John’s wort. Their structures were elucidated by UV, IR, extensive 1D and 2D NMR experiments, HRESIMS, and comparison with the literature data. The absolute configurations of 5, 8, 10, and 11 were determined by comparing experimental and calculated electronic circular dichroism spectra. Compounds 1 and 2 were synthesized regioselectively in two steps. The cytotoxicity of the crude extract (88% growth inhibition at 50 μg/mL) and of compounds 1–6, 8, 9, and 12 (no significant growth inhibition up to a concentration of 10 mM) against colon (HT-29) and prostate (PC-3) cancer cell lines was determined. No anthelmintic activity was observed for the crude extract.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 991
TI  - Prenylated phenyl polyketides and acylphloroglucinols from Hypericum peplidifolium
JO  - Phytochemistry
PY  - 2016
SP  - 108-113
AU  - Fobofou, S. A. T.
AU  - Harmon, C. R.
AU  - Lonfouo, A. H. N.
AU  - Franke, K.
AU  - Wright, S. M.
AU  - Wessjohann, L. A.
AU  - 
VL  - 124
UR  - 
DO  - 10.1016/j.phytochem.2016.02.003
AB  - In search for new or chemo-taxonomically relevant bioactive compounds from chemically unexplored Hypericum species, four previously undescribed natural products, named peplidiforones A–D were isolated and characterized from Hypericum peplidifolium A. Rich., together with six known compounds. The structures of all compounds were elucidated by extensive 1D- and 2D-NMR experiments, high resolution mass spectrometric analyses (HR-MS), and by comparison with data reported in the literature. Seven of these compounds are phenyl polyketides while three are acylphloroglucinol type compounds. Peplidiforone C, which possesses an unusual carbon skeleton consisting of a furan ring substituted by a 2,2-dimethylbut-3-enoyl moiety, is the first example of a prenylated furan derivative isolated from the genus Hypericum. The cytotoxicity, antifungal, and anti-herpes simplex virus type 1 (HSV-1) activities of extracts and compounds are described.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 989
TI  - Soft Corals Biodiversity in the Egyptian Red Sea: A Comparative MS and NMR Metabolomics Approach of Wild and Aquarium Grown Species
JO  - J. Proteome Res.
PY  - 2016
SP  - 1274-1287
AU  - Farag, M. A.
AU  - Porzel, A.
AU  - Al-Hammady, M. A.
AU  - Hegazy, M.-E. F.
AU  - Meyer, A.
AU  - Mohamed, T. A.
AU  - Westphal, H.
AU  - Wessjohann, L. A.
AU  - 
VL  - 15
UR  - 
DO  - 10.1021/acs.jproteome.6b00002
AB  - Marine life has developed unique metabolic and physiologic capabilities and advanced symbiotic relationships to survive in the varied and complex marine ecosystems. Herein, metabolite composition of the soft coral genus Sarcophyton was profiled with respect to its species and different habitats along the coastal Egyptian Red Sea via 1H NMR and ultra performance liquid chromatography-mass spectrometry (UPLC–MS) large-scale metabolomics analyses. The current study extends the application of comparative secondary metabolite profiling from plants to corals revealing for metabolite compositional differences among its species via a comparative MS and NMR approach. This was applied for the first time to investigate the metabolism of 16 Sarcophyton species in the context of their genetic diversity or growth habitat. Under optimized conditions, we were able to simultaneously identify 120 metabolites including 65 diterpenes, 8 sesquiterpenes, 18 sterols, and 15 oxylipids. Principal component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS) were used to define both similarities and differences among samples. For a compound based classification of coral species, UPLC–MS was found to be more effective than NMR. The main differentiations emanate from cembranoids and oxylipids. The specific metabolites that contribute to discrimination between soft corals of S. ehrenbergi from the three different growing habitats also belonged to cembrane type diterpenes, with aquarium S. ehrenbergi corals being less enriched in cembranoids compared to sea corals. PCA using either NMR or UPLC–MS data sets was found equally effective in predicting the species origin of unknown Sarcophyton. Cyclopropane containing sterols observed in abundance in corals may act as cellular membrane protectant against the action of coral toxins, that is, cembranoids.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 988
TI  - Metabolite profiling in 18 Saudi date palm fruit cultivars and their antioxidant potential via UPLC-qTOF-MS and multivariate data analyses
JO  - Food Funct.
PY  - 2016
SP  - 1077-1086
AU  - Farag, M. A.
AU  - Handoussa, H.
AU  - Fekry, M. I.
AU  - Wessjohann, L. A.
AU  - 
VL  - 7
UR  - 
DO  - 10.1039/c5fo01570g
AB  - Date palm fruit (Phoenix dactylifera) is not only one of the most economically significant plants in the Middle East, but also valued for its nutritional impact, and for which development of analytical methods is ongoing to help distinguish its many cultivars. This study attempts to characterize the primary and secondary metabolite profiles of 18 date cultivars from Saudi Arabia. A total of 44 metabolites extracted from the fruit peel were evaluated in a UPLC-qTOF-MS based metabolomics analysis including flavonoids, phenolic acids and fatty acids. The predominant flavones were glycosides of luteolin and chrysoeriol, as well as quercetin conjugates, whereas caffeoyl shikimic acid was the main hydroxycinnamic acid conjugate. GC-MS was further utilized to identify the primary metabolites in fruits (i.e. sugars) with glucose and fructose accounting for up to 95% of TIC among most cultivars. PCA and OPLS analyses revealed that flavone versus flavonol distribution in fruit were the main contributors for cultivar segregation. The antioxidant activity of date fruit samples was correlated with their total phenolics as determined by DPPH and CUPRAC assays. Dkheni Saudi and Shalabi Madina cultivars, appearing as the most distant in clustering analyses exhibited the strongest antioxidant effect suggesting that multivariate data analysis could help determine which date cultivars ought to be prioritized for future agricultural development.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 987
TI  - Comparative metabolite profiling and fingerprinting of genus Passiflora leaves using a multiplex approach of UPLC-MS and NMR analyzed by chemometric tools
JO  - Anal. Bioanal. Chem.
PY  - 2016
SP  - 3125-3143
AU  - Farag, M. A.
AU  - Otify, A.
AU  - Porzel, A.
AU  - Michel, C. G.
AU  - Elsayed, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 408
UR  - 
DO  - 10.1007/s00216-016-9376-4
AB  - Passiflora incarnata as well as some other Passiflora species are reported to possess anxiolytic and sedative activity and to treat various CNS disorders. The medicinal use of only a few Passiflora species has been scientifically verified. There are over 400 species in the Passiflora genus worldwide, most of which have been little characterized in terms of phytochemical or pharmacological properties. Herein, large-scale multi-targeted metabolic profiling and fingerprinting techniques were utilized to help gain a broader insight into Passiflora species leaves’ chemical composition. Nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) spectra of extracted components derived from 17 Passiflora accessions and from different geographical origins were analyzed using multivariate data analyses. A total of 78 metabolites were tentatively identified, that is, 20 C-flavonoids, 8 O-flavonoids, 21 C, O-flavonoids, 2 cyanogenic glycosides, and 23 fatty acid conjugates, of which several flavonoid conjugates are for the first time to be reported in Passiflora spp. To the best of our knowledge, this study provides the most complete map for secondary metabolite distribution within that genus. Major signals in 1H-NMR and MS spectra contributing to species discrimination were assigned to those of C-flavonoids including isovitexin-2″-O-xyloside, luteolin-C-deoxyhexoside-O-hexoside, schaftoside, isovitexin, and isoorientin. P. incarnata was found most enriched in C-flavonoids, justifying its use as an official drug within that genus. Compared to NMR, LC-MS was found more effective in sample classification based on genetic and/ or geographical origin as revealed from derived multivariate data analyses. Novel insight on metabolite candidates to mediate for Passiflora CNS sedative effects is also presented.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 986
TI  - Phenotypes on demand via switchable target protein degradation in multicellular organisms
JO  - Nat. Commun.
PY  - 2016
SP  - 12202
AU  - Faden, F.
AU  - Ramezani, T.
AU  - Mielke, S.
AU  - Almudi, I.
AU  - Nairz, K.
AU  - Froehlich, M. S.
AU  - Höckendorff, J.
AU  - Brandt, W.
AU  - Hoehenwarter, W.
AU  - Dohmen, R. J.
AU  - Schnittger, A.
AU  - Dissmeyer, N.
AU  - 
VL  - 7
UR  - 
DO  - 10.1038/ncomms12202
AB  - Phenotypes on-demand generated by controlling activation and accumulation of proteins of interest are invaluable tools to analyse and engineer biological processes. While temperature-sensitive alleles are frequently used as conditional mutants in microorganisms, they are usually difficult to identify in multicellular species. Here we present a versatile and transferable, genetically stable system based on a low-temperature-controlled N-terminal degradation signal (lt-degron) that allows reversible and switch-like tuning of protein levels under physiological conditions in vivo. Thereby, developmental effects can be triggered and phenotypes on demand generated. The lt-degron was established to produce conditional and cell-type-specific phenotypes and is generally applicable in a wide range of organisms, from eukaryotic microorganisms to plants and poikilothermic animals. We have successfully applied this system to control the abundance and function of transcription factors and different enzymes by tunable protein accumulation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 983
TI  - SBA-15 mesoporous silica particles loaded with cisplatin induce senescence in B16F10 cells
JO  - RSC Adv.
PY  - 2016
SP  - 111031-111040
AU  - Edeler, D.
AU  - Kaluđerović, M. R.
AU  - Dojčinović, B.
AU  - Schmidt, H.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 6
UR  - 
DO  - 10.1039/C6RA22596A
AB  - The anticancer drug cisplatin (CP) is loaded into SBA-15 mesoporous silica (SBA-15&#124;CP) and its release from the nanomaterial is studied. The CP-loaded SBA-15 is tested against four tumor cell lines: mouse malignant melanoma B16F10, human adenocarcinoma HeLa, colon HT-29 and prostate PC3. Most importantly, the superiority of this novel material in comparison to CP arises from the fact that the CP-grafted nanomaterial SBA-15 (→SBA-15&#124;CP) is enhancing cessation of proliferation along with induction of senescence in B16F10 in approximately 3.5 times lower concentration. The control material loaded with therapeutically inactive K2[PtCl4] (→SBA-15&#124;TC) showed no antitumor activity. To a large extent, SBA-15&#124;CP-induced senescence might present a safe approach in tumor treatment. Such cells can be cleared by immune cells resulting in efficient tumor regression. So far only apoptotic agents are being exploited in clinics, thus an understanding of the chemotherapeutic-induced senescence will allow oncologists to explore this essential tumor suppressor mechanism.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 981
TI  - A Terpene Synthase Is Involved in the Synthesis of the Volatile Organic Compound Sodorifen of Serratia plymuthica 4Rx13
JO  - Front. Microbiol.
PY  - 2016
SP  - 737
AU  - Domik, D.
AU  - Thürmer, A.
AU  - Weise, T.
AU  - Brandt, W.
AU  - Daniel, R.
AU  - Piechulla, B.
AU  - 
VL  - 7
UR  - 
DO  - 10.3389/fmicb.2016.00737
AB  - Bacteria release a plethora of volatile organic compounds, including compounds with extraordinary structures. Sodorifen (IUPAC name: 1,2,4,5,6,7,8-heptamethyl-3-methylenebicyclo[3.2.1]oct-6-ene) is a recently identified and unusual volatile hydrocarbon that is emitted by the rhizobacterium Serratia plymuthica 4R×13. Sodorifen comprises a bicyclic ring structure solely consisting of carbon and hydrogen atoms, where every carbon atom of the skeleton is substituted with either a methyl or a methylene group. This unusual feature of sodorifen made a prediction of its biosynthetic origin very difficult and so far its biosynthesis is unknown. To unravel the biosynthetic pathway we performed genome and transcriptome analyses to identify candidate genes. One knockout mutant (SOD_c20750) showed the desired negative sodorifen phenotype. Here it was shown for the first time that this gene is indispensable for the synthesis of sodorifen and strongly supports the hypothesis that sodorifen descends from the terpene metabolism. SOD_c20750 is the first bacterial terpene cyclase isolated from Serratia spp. and Enterobacteriales. Homology modeling revealed a 3D structure, which exhibits a functional role of amino acids for intermediate cation stabilization (W325) and putative proton acception (Y332). Moreover, the size and hydrophobicity of the active site strongly indicates that indeed the enzyme may catalyze the unusual compound sodorifen.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 978
TI  - CXCR4 and CXCR7 Mediate TFF3-Induced Cell Migration Independently From the ERK1/2 Signaling Pathway
JO  - Invest. Ophthalmol. Vis. Sci.
PY  - 2016
SP  - 56-65
AU  - Dieckow, J.
AU  - Brandt, W.
AU  - Hattermann, K.
AU  - Schob, S.
AU  - Schulze, U.
AU  - Mentlein, R.
AU  - Ackermann, P.
AU  - Sel, S.
AU  - Paulsen, F. P.
AU  - 
VL  - 57
UR  - 
DO  - 10.1167/iovs.15-18129
AB  - Purpose: Trefoil factor family (TFF) peptides, and in particular TFF3, are characteristic secretory products of mucous epithelia that promote antiapoptosis, epithelial migration, restitution, and wound healing. For a long time, a receptor for TFF3 had not yet been identified. However, the chemokine receptor CXCR4 has been described as a low affinity receptor for TFF2. Additionally, CXCR7, which is able to heterodimerize with CXCR4, has also been discussed as a potential TFF2 receptor. Since there are distinct structural similarities between the three known TFF peptides, this study evaluated whether CXCR4 and CXCR7 may also act as putative TFF3 receptors.Methods: We evaluated the expression of both CXCR4 and CXCR7 in samples of human ocular surface tissues and cell lines, using RT-PCR, immunohistochemistry, and Western blot analysis. Furthermore, we studied possible binding interactions between TFF3 and the receptor proteins in an x-ray structure-based modeling system. Functional studies of TFF3–CXCR4/CXCR7 interaction were accomplished by cell culture–based migration assays, flow cytometry, and evaluation of activation of the mitogen-activated protein (MAP) kinase signaling cascade.Results: We detected both receptors at mRNA and protein level in all analyzed ocular surface tissues, and in lesser amount in ocular surface cell lines. X-ray structure-based modeling revealed CXCR4 and CXCR7 dimers as possible binding partners to TFF3. Cell culture–based assays revealed enhanced cell migration under TFF3 stimulation in a conjunctival epithelial cell line, which was completely suppressed by blocking CXCR4 and/or CXCR7. Flow cytometry showed increased proliferation rates after TFF3 treatment, while blocking both receptors had no effect on this increase. Trefoil factor family 3 also activated the MAP kinase signaling cascade independently from receptor activity.Conclusions: Dimers CXCR4 and CXCR7 are involved in TFF3-dependent activation of cell migration, but not cell proliferation. The ERK1/2 pathway is activated in the process, but not influenced by CXCR4 or CXCR7. These results implicate a dependence of TFF3 activity as to cell migration on the chemokine receptors CXCR4 and CXCR7 at the ocular surface.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 973
TI  - Ericoside, a new antibacterial biflavonoid from Erica mannii (Ericaceae)
JO  - Fitoterapia
PY  - 2016
SP  - 206-211
AU  - Bitchagno, G. T. M.
AU  - Tankeo, S. B.
AU  - Tsopmo, A.
AU  - Simo Mpetga, J. D.
AU  - Tchinda, A. T.
AU  - Fobofou, S. A. T.
AU  - Nkuete, A. H. L.
AU  - Wessjohann, L. A.
AU  - Kuete, V.
AU  - Tane, P.
AU  - 
VL  - 109
UR  - 
DO  - 10.1016/j.fitote.2015.12.022
AB  - A new dihydroflavonol–flavonol biflavonoid derivative, named ericoside was isolated from the ethanol extract of the whole plant of Erica mannii along with the known flavonoid, taxifolin 3-O-α-l-rhamnopyranoside; and two readily available sterols (sitosterol, sitosterol 3-O-β-d-glucopyranoside). The isolation was performed using chromatographic methods and the structure of purified molecules were elucidated using spectroscopic techniques (e.g. MS, NMR) and by comparison with literature data. The crude ethanol extract, ericoside, and taxifolin 3-O-α-l-rhamnopyranoside were tested against ten Gram-negative bacteria including multidrug resistant clinical isolates using a broth microdilution method. The crude ethanol extract showed no noteworthy activity. Of the purified compounds, ericoside displayed moderate activity against the resistant Escherichia coli AG100 with a MIC of 64 μg/mL.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 972
TI  - A Snapshot of the Plant Glycated Proteome: STRUCTURAL, FUNCTIONAL, AND MECHANISTIC ASPECTS
JO  - J. Biol. Chem.
PY  - 2016
SP  - 7621-7636
AU  - Bilova, T.
AU  - Lukasheva, E.
AU  - Brauch, D.
AU  - Greifenhagen, U.
AU  - Paudel, G.
AU  - Tarakhovskaya, E.
AU  - Frolova, N.
AU  - Mittasch, J.
AU  - Balcke, G. U.
AU  - Tissier, A.
AU  - Osmolovskaya, N.
AU  - Vogt, T.
AU  - Wessjohann, L. A.
AU  - Birkemeyer, C.
AU  - Milkowski, C.
AU  - Frolov, A.
AU  - 
VL  - 291
UR  - 
DO  - 10.1074/jbc.M115.678581
AB  - Glycation is the reaction of carbonyl compounds (reducing sugars and α-dicarbonyls) with amino acids, lipids, and proteins, yielding early and advanced glycation end products (AGEs). The AGEs can be formed via degradation of early glycation intermediates (glycoxidation) and by interaction with the products of monosaccharide autoxidation (autoxidative glycosylation). Although formation of these potentially deleterious compounds is well characterized in animal systems and thermally treated foods, only a little information about advanced glycation in plants is available. Thus, the knowledge of the plant AGE patterns and the underlying pathways of their formation are completely missing. To fill this gap, we describe the AGE-modified proteome of Brassica napus and characterize individual sites of advanced glycation by the methods of liquid chromatography-based bottom-up proteomics. The modification patterns were complex but reproducible: 789 AGE-modified peptides in 772 proteins were detected in two independent experiments. In contrast, only 168 polypeptides contained early glycated lysines, which did not resemble the sites of advanced glycation. Similar observations were made with Arabidopsis thaliana. The absence of the early glycated precursors of the AGE-modified protein residues indicated autoxidative glycosylation, but not glycoxidation, as the major pathway of AGE formation. To prove this assumption and to identify the potential modifying agents, we estimated the reactivity and glycative potential of plant-derived sugars using a model peptide approach and liquid chromatography-mass spectrometry-based techniques. Evaluation of these data sets together with the assessed tissue carbohydrate contents revealed dihydroxyacetone phosphate, glyceraldehyde 3-phosphate, ribulose, erythrose, and sucrose as potential precursors of plant AGEs.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 971
TI  - Morphometric analysis of the cerebral expression of ATP-binding cassette transporter protein ABCB1 in chronic schizophrenia: Circumscribed deficits in the habenula
JO  - Schizophr. Res.
PY  - 2016
SP  - 52-58
AU  - Bernstein, H.-G.
AU  - Hildebrandt, J.
AU  - Dobrowolny, H.
AU  - Steiner, J.
AU  - Bogerts, B.
AU  - Pahnke, J.
AU  - 
VL  - 177
UR  - 
DO  - 10.1016/j.schres.2016.02.036
AB  - There is increasing evidence that microvascular abnormalities and malfunction of the blood–brain barrier (BBB) significantly contribute to schizophrenia pathophysiology. The ATP-binding cassette transporter ABCB1 is an important molecular component of the intact BBB, which has been implicated in a number of neurodegenerative and psychiatric disorders, including schizophrenia. However, the regional and cellular expression of ABCB1 in schizophrenia is yet unexplored. Therefore, we studied ABCB1 protein expression immunohistochemically in twelve human post-mortem brain regions known to play a role in schizophrenia, in 13 patients with schizophrenia and nine controls. In ten out of twelve brain regions under study, no significant differences were found with regard to the numerical density of ABCB1-expressing capillaries between all patients with schizophrenia and control cases. The left and right habenular complex, however, showed significantly reduced capillary densities in schizophrenia patients. In addition, we found a significantly reduced density of ABCB1-expressing neurons in the left habenula. Reduced ABCB1 expression in habenular capillaries might contribute to increased brain levels of proinflammatory cytokines in patients with schizophrenia, while decreased expression of this protein in a subpopulation of medial habenular neurons (which are probably purinergic) might be related to abnormalities of purines and their receptors found in this disease.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 969
TI  - Evaluation of functionalized mesoporous silica SBA-15 as a carrier system for Ph3Sn(CH2)3OH against the A2780 ovarian carcinoma cell line
JO  - Dalton Trans.
PY  - 2016
SP  - 18984-18993
AU  - Bensing, C.
AU  - Mojić, M.
AU  - Gómez-Ruiz, S.
AU  - Carralero, S.
AU  - Dojčinović, B.
AU  - Maksimović-Ivanić, D.
AU  - Mijatović, S.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 45
UR  - 
DO  - 10.1039/C6DT03519A
AB  - SBA-15&#124;Sn3, a mesoporous silica-based material (derivative of SBA-15) loaded with an organotin compound Ph3Sn(CH2)3OH (Sn3), possesses improved antitumor potential against the A2780 high-grade serous ovarian carcinoma cell line in comparison to Sn3. It is demonstrated that both the compound and the nanostructured material are internalized by the A2780 cells. A similar mode of action of Sn3 and SBA-15&#124;Sn3 against the A2780 cell line was found. Explicitly, induction of apoptosis, caspase 2, 3, 8 and 9 activation, accumulation of cells in the hypodiploid phase as well as accumulation of ROS were observed. Interestingly, Sn3 loaded in the mesoporous silica-based material needed to reach a concentration 3.5 times lower than the IC50 value of the Sn3 compound, pointing out a higher effect of the SBA-15&#124;Sn3 than Sn3 alone. Clonogenic potential, growth in 3D culture as well as mobility of cells were disturbed in the presence of SBA-15&#124;Sn3. Such behavior could be associated with the suppression of p-38 MAPK. Less profound effect of Sn3 compared to SBA-15&#124;Sn3 could be attributed to a different regulation of p-38 and STAT-3, which are mainly responsible for an appropriate cellular response to diverse stimuli or metastatic properties.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 966
TI  - Chemistry of the earthy odour of basidiomata of Cortinarius hinnuleus (Basidiomycota, Agaricales)
JO  - Österr. Z. Pilzk.
PY  - 2016
SP  - 5-10
AU  - Arnold, N.
AU  - Palfner, G.
AU  - Kuhnt, C.
AU  - Schmidt, J.
AU  - 
VL  - 25
UR  - http://www.univie.ac.at/oemykges/wp-content/uploads/2016/11/ozp_25_OA_Arnold_Cortinarius_odor.pdf
AB  - Cortinarius hinnuleus (Earthy Webcap), a common mycorrhizal mushroom in Central Europe, is characterized by a mouldy earthy odour. The relevant volatile compounds were detected by gas chromatography-mass spectrometry using headspace-solid phase microextraction technology and identified as geosmin, ß-caryophyllene and ß-barbatene together with the C8-volatiles 1-octen-3-ol, 1-octen-3-one, octan-3-ol, octan-3-one, and 2-octen-1-ol.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 965
TI  - Bioactive Triterpenes from the Fungus Piptoporus betulinus
JO  - Rec. Nat. Prod.
PY  - 2016
SP  - 103-108
AU  - Alresly, Z.
AU  - Lindequist, U.
AU  - Lalk, M.
AU  - Porzel, A.
AU  - Arnold, N.
AU  - Wessjohann, L. A.
AU  - 
VL  - 10
UR  - http://www.acgpubs.org/article/records-of-natural-products/2016/1-january-february/bioactive-triterpenes-from-the-fungus-piptoporus-betulinus
AB  - Phytochemical investigation of the ethyl acetate extract of the fruiting bodies from the basidiomycete Piptoporus betulinus led to the isolation of a new bioactive lanostane triterpene identified as 3 b -acetoxy-16-hydroxy-24-oxo-5α-lanosta-8- ene-21-oic acid (1). In addition, ten known triterpenes, polyporenic acid A (5), polyporenic acid C (4), three derivatives of polyporenic acid A (8, 10, 11), betulinic acid (3), betulin (2), ergosterol peroxide (6), 9,11-dehydroergosterol peroxide (7), and fomefficinic acid (9), were also isolated from the fungus. All isolated compounds were tested for antimicrobial activity against some Gram-positive and Gram-negative bacteria as well as against a fungal strain. The new triterpene and some of the other compounds showed antimicrobial activity against Gram-positive bacteria.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 964
TI  - Chemical composition and biological activity of essential oil of Chenopodium ambrosioides from Yemen
JO  - Am. J. Essent. Oils Nat. Prod.
PY  - 2016
SP  - 20-22
AU  - Al-kaf, A. G.
AU  - Crouch, R. A.
AU  - Denkert, A.
AU  - Porzel, A.
AU  - Al-Hawshabi, O. S. S.
AU  - Ali, N. A. A.
AU  - Setzer, W. N.
AU  - Wessjohann, L.
AU  - 
VL  - 4
UR  - http://www.essencejournal.com/archives/2016/4/1/A/3-1-10
AB  - The chemical composition of the hydrodistilled leaf essential oil from Chenopodium ambrosioides L. growing wild in Yemen was determined by GC-MS analysis, and its cytotoxic, and general antioxidant potential were evaluated. Major compounds of C. ambrosioides oil were ascaridole (54.2%), isoascaridole (27.7%) and p-cymene (8.1%). At concentrations of 50 and 25 μg/mL, the essential oil showed cytotoxic activity against HT29 (human colon adenocarcinoma cells), with growth inhibition of 100 and 56% (± 3). The free radical scavenging ability of the oil was assessed by the DPPH assay to show antiradical activity with IC50 of 10.4 μg/mL. TLC-bioautographic assay was used to identify the acetylcholinesterase inhibitory effect, and ascaridole was isolated and characterized (ESIMS, 1H NMR, 13C NMR and HMBC) as the responsible constituent for anticholinesterase activity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 963
TI  - Ethnobotany, chemical constituents and biological activities of the flowers of Hydnora abyssinica A.Br. (Hydnoraceae)
JO  - Pharmazie
PY  - 2016
SP  - 222-226
AU  - Al-Fatimi, M.
AU  - Ali, N. A. A.
AU  - Kilian, N.
AU  - Franke, K.
AU  - Arnold, N.
AU  - Kuhnt, C.
AU  - Schmidt, J.
AU  - Lindequist, U.
AU  - 
VL  - 71
UR  - 
DO  - 10.1691/ph.2016.5808
AB  - Hydnora abyssinica A.Br. (Hydnoraceae), a holoparasitic herb, is for the first time recorded for Abyan governorate of South Yemen. Flowers of this species were studied for their ethnobotanical, biological and chemical properties for the first time. In South Yemen, they are traditionally used as wild food and to cure stomach diseases, gastric ulcer and cancer. Phytochemical analysis of the extracts showed the presence of terpenes, tannins, phenols, and flavonoids. The volatile components of the air-dried powdered flowers were identified using a static headspace GC/MS analysis as acetic acid, ethyl acetate, sabinene, α-terpinene, (+)-D-limonene and γ-terpinene. These volatile compounds that characterize the odor and taste of the flowers were detected for the first time in a species of the family Hydnoraceae. The flowers were extracted by n-hexane, dichlormethane, ethyl acetate, ethanol, methanol and water. With exception of the water extract all extracts demonstrated activities against Gram-positive bacteria as well as remarkable radical scavenging activities in DPPH assay. Ethyl acetate, methanol and water extracts exhibited good antifungal activities. The cytotoxic activity of the extracts against FL cells, measured in neutral red assay, was only weak (IC50 &gt; 500 μg /mL). The results justify the traditional use of the flowers of Hydnora abyssinica  in South Yemen.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 962
TI  - Stereoselective glycoconjugation of steroids with selenocarbohydrates
JO  - RSC Adv.
PY  - 2016
SP  - 93905-93914
AU  - Affeldt, R. F.
AU  - Santos, F. P.
AU  - da Silva, R. S.
AU  - Rodrigues, O. E. D.
AU  - Wessjohann, L. A.
AU  - Lüdtke, D. S.
AU  - 
VL  - 6
UR  - 
DO  - 10.1039/C6RA21485A
AB  - A methodology that brings together sugar and steroid scaffolds linked by a selenium atom is discussed in this work. A series of 6β and 3α glycoconjugated steroids were achieved by stereoselective nucleophilic substitution of cholesterol, pregnenolone, stigmasterol and sitosterol with different seleno-pyranosides and furanosides.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1043
TI  - Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast
JO  - Nat. Commun.
PY  - 2016
SP  - 12942
AU  - Scheler, U.
AU  - Brandt, W.
AU  - Porzel, A.
AU  - Rothe, K.
AU  - Manzano, D.
AU  - Božić, D.
AU  - Papaefthimiou, D.
AU  - Balcke, G. U.
AU  - Henning, A.
AU  - Lohse, S.
AU  - Marillonnet, S.
AU  - Kanellis, A. K.
AU  - Ferrer, A.
AU  - Tissier, A.
AU  - 
VL  - 7
UR  - 
DO  - 10.1038/ncomms12942
AB  - Rosemary extracts containing the phenolic diterpenes carnosic acid and its derivative carnosol are approved food additives used in an increasingly wide range of products to enhance shelf-life, thanks to their high anti-oxidant activity. We describe here the elucidation of the complete biosynthetic pathway of carnosic acid and its reconstitution in yeast cells. Cytochrome P450 oxygenases (CYP76AH22-24) from Rosmarinus officinalis and Salvia fruticosa already characterized as ferruginol synthases are also able to produce 11-hydroxyferruginol. Modelling-based mutagenesis of three amino acids in the related ferruginol synthase (CYP76AH1) from S. miltiorrhiza is sufficient to convert it to a 11-hydroxyferruginol synthase (HFS). The three sequential C20 oxidations for the conversion of 11-hydroxyferruginol to carnosic acid are catalysed by the related CYP76AK6-8. The availability of the genes for the biosynthesis of carnosic acid opens opportunities for the metabolic engineering of phenolic diterpenes, a class of compounds with potent anti-oxidant, anti-inflammatory and anti-tumour activities.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1037
TI  - Pyrofomins A-D, polyoxygenated sesquiterpenoids from Pyrofomes demidoffii
JO  - Fitoterapia
PY  - 2016
SP  - 229-232
AU  - Quang, D. N.
AU  - Wagner, C.
AU  - Merzweiler, K.
AU  - Abate, D.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Arnold, N.
AU  - 
VL  - 112
UR  - 
DO  - 10.1016/j.fitote.2016.06.004
AB  - Pyrofomins A-D, four polyoxygenated sesquiterpenoids have been isolated from the methanolic extract of the fruit bodies of Pyrofomes demidoffii. Their structures are elucidated by IR, HR-FTICR-MS, and 2D NMR spectroscopy. Furthermore, the cedrane carbon skeleton of pyrofomin A (1) is confirmed by X-ray crystallographic analysis. The sesquiterpenoids 1–4 show neither cytotoxicity against KB cells nor antimicrobial activity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1036
TI  - The α-Terpineol to 1,8-Cineole Cyclization Reaction of Tobacco Terpene Synthases
JO  - Plant Physiol.
PY  - 2016
SP  - 2120-2131
AU  - Piechulla, B.
AU  - Bartelt, R.
AU  - Brosemann, A.
AU  - Effmert, U.
AU  - Bouwmeester, H.
AU  - Hippauf, F.
AU  - Brandt, W.
AU  - 
VL  - 172
UR  - 
DO  - 10.1104/pp.16.01378
AB  - Flowers of Nicotiana species emit a characteristic blend including the cineole cassette monoterpenes. This set of terpenes is synthesized by multiproduct enzymes, with either 1,8-cineole or α-terpineol contributing most to the volatile spectrum, thus referring to cineole or terpineol synthase, respectively. To understand the molecular and structural requirements of the enzymes that favor the biochemical formation of α-terpineol and 1,8-cineole, site-directed mutagenesis, in silico modeling, and semiempiric calculations were performed. Our results indicate the formation of α-terpineol by a nucleophilic attack of water. During this attack, the α-terpinyl cation is stabilized by π-stacking with a tryptophan side chain (tryptophan-253). The hypothesized catalytic mechanism of α-terpineol-to-1,8-cineole conversion is initiated by a catalytic dyad (histidine-502 and glutamate-249), acting as a base, and a threonine (threonine-278) providing the subsequent rearrangement from terpineol to cineol by catalyzing the autoprotonation of (S)-(−)-α-terpineol, which is the favored enantiomer product of the recombinant enzymes. Furthermore, by site-directed mutagenesis, we were able to identify amino acids at positions 147, 148, and 266 that determine the different terpineol-cineole ratios in Nicotianasuaveolens cineole synthase and Nicotianalangsdorffii terpineol synthase. Since amino acid 266 is more than 10 Å away from the active site, an indirect effect of this amino acid exchange on the catalysis is discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1033
TI  - Osmotic stress is accompanied by protein glycation in Arabidopsis thaliana
JO  - J. Exp. Bot.
PY  - 2016
SP  - 6283-6295
AU  - Paudel, G.
AU  - Bilova, T.
AU  - Schmidt, R.
AU  - Greifenhagen, U.
AU  - Berger, R.
AU  - Tarakhovskaya, E.
AU  - Stöckhardt, S.
AU  - Balcke, G. U.
AU  - Humbeck, K.
AU  - Brandt, W.
AU  - Sinz, A.
AU  - Vogt, T.
AU  - Birkemeyer, C.
AU  - Wessjohann, L.
AU  - Frolov, A.
AU  - 
VL  - 67
UR  - 
DO  - 10.1093/jxb/erw395
AB  - Among the environmental alterations accompanying oncoming climate changes, drought is the most important factor influencing crop plant productivity. In plants, water deficit ultimately results in the development of oxidative stress and accumulation of osmolytes (e.g. amino acids and carbohydrates) in all tissues. Up-regulation of sugar biosynthesis in parallel to the increasing overproduction of reactive oxygen species (ROS) might enhance protein glycation, i.e. interaction of carbonyl compounds, reducing sugars and α-dicarbonyls with lysyl and arginyl side-chains yielding early (Amadori and Heyns compounds) and advanced glycation end-products (AGEs). Although the constitutive plant protein glycation patterns were characterized recently, the effects of environmental stress on AGE formation are unknown so far. To fill this gap, we present here a comprehensive in-depth study of the changes in Arabidopsis thaliana advanced glycated proteome related to osmotic stress. A 3 d application of osmotic stress revealed 31 stress-specifically and 12 differentially AGE-modified proteins, representing altogether 56 advanced glycation sites. Based on proteomic and metabolomic results, in combination with biochemical, enzymatic and gene expression analysis, we propose monosaccharide autoxidation as the main stress-related glycation mechanism, and glyoxal as the major glycation agent in plants subjected to drought.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1032
TI  - Electrochemical properties of some gold(III) complexes with (S,S)-R2edda-type ligands
JO  - Int. J. Electrochem. Sci.
PY  - 2016
SP  - 1162-1171
AU  - Pantelić, N.
AU  - Stanković, D. M.
AU  - Zmejkovski, B. B.
AU  - Kaluđerović, G. N.
AU  - Sabo, T. J.
AU  - 
VL  - 11
UR  - http://www.electrochemsci.org/list16.htm#issue2
AB  - Oxidation-reduction properties of eleven gold(III) complexes with (S,S)-R2edda-type ligands was studied by cyclic and differential pulse voltammetry in DMSO. Series I: [AuCl2{(S,S)-R2eddip}]PF6, (S,S)-eddip = (S,S)-ethylenediamine-N,N’-di-2-propanoate, R = n-butyl, n-pentyl, isobutyl, isoamyl, cyclopentyl, 1–5; II: [AuCl2{(S,S)-R2eddch}]PF6, (S,S)-eddch = (S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate, R = methyl, ethyl, n-propyl, n-butyl, isobutyl, isoamyl, 6–11. Voltammograms in DMSO showed two successive irreversible reduction steps, where AuI species were the final reduction product. Reduction potential values are in range from 116 to 156 mV (Ep1) and –520 to –572 mV (Ep2) for Series I and from 148 to 228 mV (Ep1) and –569 to –638 mV (Ep2) for Series II. In general, slightly easier reduction of complexes belonging to Series I (higher cytotoxicity) could be due to less steric hindrance around the gold center. Reduction potentials and anticancer activity are not in correlation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1031
TI  - Synthesis, Characterization, and Cytotoxicity of a Novel Gold(III) Complex with O,O′-Diethyl Ester of Ethylenediamine-N,N′-Di-2-(4-Methyl)Pentanoic Acid
JO  - Metals
PY  - 2016
SP  - 226
AU  - Pantelić, N.
AU  - Zmejkovski, B. B.
AU  - Marković, D. D.
AU  - Vujić, J. M.
AU  - Stanojković, T. P.
AU  - Sabo, T. J.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 6
UR  - 
DO  - 10.3390/met6090226
AB  - A novel gold(III) complex, [AuCl2{(S,S)-Et2eddl}]PF6, ((S,S)-Et2eddl = O,O′-diethyl ester of ethylenediamine-N,N′-di-2-(4-methyl)pentanoic acid) was synthesized and characterized by IR, 1D (1H and 13C), and 2D (H,H-COSY and H,H-NOESY) NMR spectroscopy, mass spectrometry, and elemental analysis. Density functional theory calculations confirmed that (R,R)-N,N′ diastereoisomer was energetically the most stable isomer. In vitro antitumor action of ligand precursor [(S,S)-H2Et2eddl]Cl2 and corresponding gold(III) complex was determined against tumor cell lines: human adenocarcinoma (HeLa), human colon carcinoma (LS174), human breast cancer (MCF7), non-small cell lung carcinoma cell line (A549), and non-cancerous cell line human embryonic lung fibroblast (MRC-5) using microculture tetrazolium test (MTT) assay. The results indicate that both ligand precursor and gold(III) complex have showed very good to moderate cytotoxic activity against all tested malignant cell lines. The highest activity was expressed by [AuCl2{(S,S)-Et2eddl}]PF6 against the LS174 cells, with IC50 value of 7.4 ± 1.2 µM.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1030
TI  - Tulasporins A–D, 19-Residue Peptaibols from the Mycoparasitic Fungus Sepedonium tulasneanum
JO  - Nat. Prod. Commun.
PY  - 2016
SP  - 1821-1824
AU  - Otto, A.
AU  - Laub, A.
AU  - Haid, M.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Wessjohann, L.
AU  - Arnold, N.
AU  - 
VL  - 11
UR  - 
DO  - 10.1177/1934578X1601101212
AB  - Four new 19-residue peptaibols, named tulasporins A–D (1–4), were isolated from the semi-solid cultures of Sepedonium tulasneanum. Their structures were elucidated on the basis of extensive ESI-HRMSn fragmentation studies as well as 1H NMR spectroscopic analyses. Interestingly, the structures of tulasporins A–D (1–4) resemble those of chrysospermins isolated earlier from cultures of S. chrysospermum. Previously, it was hypothesized that the peptaibol production by Sepedonium species correlates with the morphology of the aleurioconidia, as exclusively round-shaped aleurioconidia forming species produced peptaibols. Since the investigated Sepedonium tulasneanum produces oval aleurioconidia, this study can be considered as the first report of peptaibols from a Sepedonium strain with oval-shaped aleurioconidia. Thus, it could be demonstrated that both round as well as oval aleurioconidia forming Sepedonium species are able to produce peptaibols. Tulasporins A-D (1–4), when tested against phytopathogenic fungi, exhibited good growth inhibitory activity against both Botrytis cinerea and Phytophthora infestans, while they were devoid of significant activity against Septoria tritici.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1029
TI  - Structure and Absolute Configuration of Pseudohygrophorones A12 and B12, Alkyl Cyclohexenone Derivatives from Hygrophorus abieticola (Basidiomycetes)
JO  - J. Nat. Prod.
PY  - 2016
SP  - 74-80
AU  - Otto, A.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Brandt, W.
AU  - Wessjohann, L.
AU  - Arnold, N.
AU  - 
VL  - 79
UR  - 
DO  - 10.1021/acs.jnatprod.5b00675
AB  - Pseudohygrophorones A(12) (1) and B(12) (2), the first naturally occurring alkyl cyclohexenones from a fungal source, and the recently reported hygrophorone B(12) (3) have been isolated from fruiting bodies of the basidiomycete Hygrophorus abieticola Krieglst. ex Gröger &amp; Bresinsky. Their structures were assigned on the basis of extensive one- and two-dimensional NMR spectroscopic analysis as well as ESI-HRMS measurements. The absolute configuration of the three stereogenic centers in the diastereomeric compounds 1 and 2 was established with the aid of (3)JH,H and (4)JH,H coupling constants, NOE interactions, and conformational analysis in conjunction with quantum chemical CD calculations. It was concluded that pseudohygrophorone A(12) (1) is 4S,5S,6S configured, while pseudohygrophorone B(12) (2) was identified as the C-6 epimer of 1, corresponding to the absolute configuration 4S,5S,6R. In addition, the mass spectrometric fragmentation behavior of 1-3 obtained by the higher energy collisional dissociation method allows a clear distinction between the pseudohygrophorones (1 and 2) and hygrophorone B(12) (3). The isolated compounds 1-3 exhibited pronounced activity against phytopathogenic organisms.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1028
TI  - Chilenopeptins A and B, Peptaibols from the Chilean Sepedonium aff. chalcipori KSH 883
JO  - J. Nat. Prod.
PY  - 2016
SP  - 929-938
AU  - Otto, A.
AU  - Laub, A.
AU  - Wendt, L.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Palfner, G.
AU  - Becerra, J.
AU  - Krüger, D.
AU  - Stadler, M.
AU  - Wessjohann, L.
AU  - Westermann, B.
AU  - Arnold, N.
AU  - 
VL  - 79
UR  - 
DO  - 10.1021/acs.jnatprod.5b01018
AB  - The Chilean Sepedonium aff. chalcipori strain KSH 883, isolated from the endemic Boletus loyo Philippi, was studied in a polythetic approach based on chemical, molecular, and biological data. A taxonomic study of the strain using molecular data of the ITS, EF1-α, and RPB2 barcoding genes confirmed the position of the isolated strain within the S. chalcipori clade, but also suggested the separation of this clade into three different species. Two new linear 15-residue peptaibols, named chilenopeptins A (1) and B (2), together with the known peptaibols tylopeptins A (3) and B (4) were isolated from the semisolid culture of strain KSH 883. The structures of 1 and 2 were elucidated on the basis of HRESIMS(n) experiments in conjunction with comprehensive 1D and 2D NMR analysis. Thus, the sequence of chilenopeptin A (1) was identified as Ac-Aib(1)-Ser(2)-Trp(3)-Aib(4)-Pro(5)-Leu(6)-Aib(7)-Aib(8)-Gln(9)-Aib(10)-Aib(11)-Gln(12)-Aib(13)-Leu(14)-Pheol(15), while chilenopeptin B (2) differs from 1 by the replacement of Trp(3) by Phe(3). Additionally, the total synthesis of 1 and 2 was accomplished by a solid-phase approach, confirming the absolute configuration of all chiral amino acids as l. Both the chilenopeptins (1 and 2) and tylopeptins (3 and 4) were evaluated for their potential to inhibit the growth of phytopathogenic organisms.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 58
TI  - Biocatalytic Synthesis of Natural Products by O-Methyltransferases
T2  - Applied Biocatalysis: From Fundamental Science to Industrial Applications: From Fundamental Science to Industrial Applications
PB  - 
PY  - 2016
SP  - 121-146
AU  - Wessjohann, L.
AU  - Bauer, A.-K.
AU  - Dippe, M.
AU  - Ley, J.
AU  - Geißler, T.
AU  - 
VL  - 
UR  - 
SN  - 9783527677122
DO  - 10.1002/9783527677122.ch7
AB  - O‐Methylation is a crucial step to introduce specific target binding properties as well as physicochemical changes in bioactive natural products, such as aroma compounds or CNS‐active alkaloids. The corresponding O‐methyltransferases, especially those acting on catechol groups to produce vanilloid or isovanilloid moieties, are well behaved enzymes, suitable for scale‐up and heterologous expression in standard production organisms. The chapter lists the currently known applications. It focuses on examples where O‐methyltransferases are applied in the production of bioactive (natural) compounds in vitro and in vivo, with an emphasis on O‐methylated phenylpropanoids with flavonoids, and alkaloids including morphine relatives.The major drawback for large scale application lies in the availability or regeneration of the cofactor S‐adenosylmethionine (SAM). Its biotechnological production and in situ generation therefore is discussed in detail. Furthermore upstream bottlenecks like regioselective enzymatic hydroxylation to form substrates for O‐methylation, or downstream oxidation to form methylene dioxy groups, are shortly discussed.
A2  - Hilterhaus, L., et al., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 53
TI  - Der WissenschaftsCampus Halle – Pflanzenbasierte Bioökonomie: Vom Molekül zur Gesellschaft – Wege zu einer pflanzenbasierten Wirtschaft
T2  - Bioökonomie: Welche Bedeutung haben die Agrar- und Forstwissenschaften?
PB  - Agrarspectrum des DAF
PY  - 2016
SP  - 99-112
AU  - Pillen, K.
AU  - Sonntag, N.
AU  - Flügel, C.
AU  - Tissier, A.-L.
AU  - Wessjohann, L.
AU  - 
VL  - 48
UR  - 
AB  - 
A2  - Christen, O., et al., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 46
TI  - Glycation of Plant Proteins under Environmental Stress — Methodological Approaches, Potential Mechanisms and Biological Role
T2  - Abiotic and Biotic Stress in Plants - Recent Advances and Future Perspectives
PB  - 
PY  - 2016
SP  - 295-316
AU  - Bilova, T.
AU  - Greifenhagen, U.
AU  - Paudel, G.
AU  - Lukasheva, E.
AU  - Brauch, D.
AU  - Osmolovskaya, N.
AU  - Tarakhovskaya, E.
AU  - Balcke, G. U.
AU  - Tissier, A.
AU  - Vogt, T.
AU  - Milkowski, C.
AU  - Birkemeyer, C.
AU  - Wessjohann, L.
AU  - Frolov, A.
AU  - 
VL  - 
UR  - 
DO  - 10.5772/61860
AB  - Environmental stress is one of the major factors reducing crop productivity. Due to the oncoming climate changes, the effects of drought and high light on plants play an increasing role in modern agriculture. These changes are accompanied with a progressing contamination of soils with heavy metals. Independent of their nature, environmental alterations result in development of oxidative stress, i.e. increase of reactive oxygen species (ROS) contents, and metabolic adjustment, i.e. accumulation of soluble primary metabolites (amino acids and sugars). However, a simultaneous increase of ROS and sugar concentrations ultimately results in protein glycation, i.e. non-enzymatic interaction of reducing sugars or their degradation products (α-dicarbonyls) with proteins. The eventually resulting advanced glycation end-products (AGEs) are known to be toxic and pro-inflammatory in mammals. Recently, their presence was unambiguously demonstrated in vivo in stressed Arabidopsis thaliana plants. Currently, information on protein targets, modification sites therein, mediators and mechanisms of plant glycation are being intensively studied. In this chapter, we comprehensively review the methodological approaches for plant glycation research and discuss potential mechanisms of AGE formation under stress conditions. On the basis of these patterns and additional in vitro experiments, the pathways and mechanisms of plant glycation can be proposed.
A2  - Shanker, A. K. &amp; Shanker, C., eds.
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1174
TI  - Identification, Functional Characterization, and Evolution of Terpene Synthases from a Basal Dicot
JO  - Plant Physiol.
PY  - 2015
SP  - 1683-1697
AU  - Yahyaa, M.
AU  - Matsuba, Y.
AU  - Brandt, W.
AU  - Doron-Faigenboim, A.
AU  - Bar, E.
AU  - McClain, A.
AU  - Davidovich-Rikanati, R.
AU  - Lewinsohn, E.
AU  - Pichersky, E.
AU  - Ibdah, M.
AU  - 
VL  - 169
UR  - 
DO  - 10.1104/pp.15.00930
AB  - Bay laurel (Laurus nobilis) is an agriculturally and economically important dioecious tree in the basal dicot family Lauraceae used in food and drugs and in the cosmetics industry. Bay leaves, with their abundant monoterpenes and sesquiterpenes, are used to impart flavor and aroma to food, and have also drawn attention in recent years because of their potential pharmaceutical applications. To identify terpene synthases (TPSs) involved in the production of these volatile terpenes, we performed RNA sequencing to profile the transcriptome of L. nobilis leaves. Bioinformatic analysis led to the identification of eight TPS complementary DNAs. We characterized the enzymes encoded by three of these complementary DNAs: a monoterpene synthase that belongs to the TPS-b clade catalyzes the formation of mostly 1,8-cineole; a sesquiterpene synthase belonging to the TPS-a clade catalyzes the formation of mainly cadinenes; and a diterpene synthase of the TPS-e/f clade catalyzes the formation of geranyllinalool. Comparison of the sequences of these three TPSs indicated that the TPS-a and TPS-b clades of the TPS gene family evolved early in the evolution of the angiosperm lineage, and that geranyllinalool synthase activity is the likely ancestral function in angiosperms of genes belonging to an ancient TPS-e/f subclade that diverged from the kaurene synthase gene lineages before the split of angiosperms and gymnosperms.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1173
TI  - Detection of a New Piperideine Alkaloid in the Pygidial Glands of Some Stenus Beetles
JO  - Chem. Biodivers.
PY  - 2015
SP  - 1422-1434
AU  - Wittmann, I.
AU  - Schierling, A.
AU  - Dettner, K.
AU  - Göhl, M.
AU  - Schmidt, J.
AU  - Seifert, K.
AU  - 
VL  - 12
UR  - 
DO  - 10.1002/cbdv.201400391
AB  - Rove beetles of the genus Stenus produce and store bioactive alkaloids like stenusine (3), 3‐(2‐methylbut‐1‐enyl)pyridine (4), and cicindeloine (5) in their pygidial glands to protect themselves from predation and microorganismic infestation.The biosynthesis of stenusine (3), 3‐(2‐methylbut‐1‐enyl)pyridine (4), and cicindeloine (5) was previously investigated in Stenus bimaculatus, Stenus similis, and Stenus solutus, respectively. The piperideine alkaloid cicindeloine (5) occurs also as a major compound in the pygidial gland secretion of Stenus cicindeloides. The three metabolites follow the same biosynthetic pathway, where the N‐heterocyclic ring is derived from L‐lysine and the side chain from L‐isoleucine. The different alkaloids are finally obtained by few modifications of shared precursor molecules, such as 2,3,4,5‐tetrahydro‐5‐(2‐methylbutylidene)pyridine (1). This piperideine alkaloid was synthesized and detected by GC/MS and GC at a chiral phase in the pygidial glands of Stenus similis, Stenus tarsalis, and Stenus cicindeloides.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1171
TI  - Synthesis of substituted imidazolines by an Ugi/Staudinger/aza-Wittig sequence
JO  - Tetrahedron Lett.
PY  - 2015
SP  - 1025-1029
AU  - Welsch, S. J.
AU  - Umkehrer, M.
AU  - Kalinski, C.
AU  - Ross, G.
AU  - Burdack, C.
AU  - Kolb, J.
AU  - Wild, M.
AU  - Ehrlich, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 56
UR  - 
DO  - 10.1016/j.tetlet.2015.01.043
AB  - A series of 2-(acetamide-2-yl)-imidazolines (II) with 5 points of diversity were prepared by an Ugi-4CR–Staudinger–aza-Wittig-sequence starting from simple azidoalkylamines. The intramolecular aza-Wittig cyclization between the iminophosphane and the tertiary amide of the Ugi product (I) was effected by short microwave irradiation. Competitive cyclization to the secondary amide was not relevant, however, in some cases subsequent formation of the bicyclic ortho-amidines (III) was observed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1164
TI  - Inhibition of a multiproduct terpene synthase from Medicago truncatula by 3-bromoprenyl diphosphates
JO  - Org. Biomol. Chem.
PY  - 2015
SP  - 4776-4784
AU  - Vattekkatte, A.
AU  - Gatto, N.
AU  - Schulze, E.
AU  - Brandt, W.
AU  - Boland, W.
AU  - 
VL  - 13
UR  - 
DO  - 10.1039/c5ob00506j
AB  - The multiproduct sesquiterpene synthase MtTPS5 from Medicago truncatula catalyzes the conversion of farnesyl diphosphate (FDP) into a complex mixture of 27 terpenoids. 3-Bromo substrate analogues of geranyl diphosphate (3-BrGDP) and farnesyl diphosphate (3-BrFDP) were evaluated as substrates of MTPS5 enzyme. Kinetic studies demonstrated that these compounds were highly potent competitive inhibitors of the MtTPS5 enzyme with fast binding and slow reversibility. Since there is a lack of knowledge about the crystal structure of multiproduct terpene synthases, these molecules might be ideal candidates for obtaining a co-crystal structure with multiproduct terpene synthases. Due to the structural and mechanistic similarity between various terpene synthases we expect these 3-bromo isoprenoids to be ideal probes for crystal structure studies.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1163
TI  - Macrocyclization of Peptide Side Chains by the Ugi Reaction: Achieving Peptide Folding and Exocyclic N-Functionalization in One Shot
JO  - J. Org. Chem.
PY  - 2015
SP  - 6697-6707
AU  - Vasco, A. V.
AU  - Pérez, C. S.
AU  - Morales, F. E.
AU  - Garay, H. E.
AU  - Vasilev, D.
AU  - Gavín, J. A.
AU  - Wessjohann, L. A.
AU  - Rivera, D. G.
AU  - 
VL  - 80
UR  - 
DO  - 10.1021/acs.joc.5b00858
AB  - The cyclization of peptide side chains has been traditionally used to either induce or stabilize secondary structures (β-strands, helices, reverse turns) in short peptide sequences. So far, classic peptide coupling, nucleophilic substitution, olefin metathesis, and click reactions have been the methods of choice to fold synthetic peptides by means of macrocyclization. This article describes the utilization of the Ugi reaction for the side chain-to-side chain and side chain-to-termini macrocyclization of peptides, thus enabling not only access to stable folded structures but also the incorporation of exocyclic functionalities as N-substituents. Analysis of the NMR-derived structures revealed the formation of helical turns, β-bulges, and α-turns in cyclic peptides cross-linked at i, i + 3 and i, i + 4 positions, proving the folding effect of the multicomponent Ugi macrocyclization. Molecular dynamics simulation provided further insights on the stability and molecular motion of the side chain cross-linked peptides.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1160
TI  - Draft Genome Sequence of Streptomyces sp. Strain 150FB, a Mushroom Mycoparasite Antagonist
JO  - Genome Announc.
PY  - 2015
SP  - e01441-14
AU  - Tarkka, M. T.
AU  - Feldhahn, L.
AU  - Krüger, D.
AU  - Arnold, N.
AU  - Buscot, F.
AU  - Wubet, T.
AU  - 
VL  - 3
UR  - 
DO  - 10.1128/genomeA.01441-14
AB  - Streptomyces sp. strain 150FB, isolated from the cap surface of a bolete mushroom, inhibits the growth of the mycoparasitic Sepedonium species. Functional annotation of the strain 150FB draft genome identified 22 putative secondary metabolite biosynthetic gene clusters and genes encoding secreted proteins, which may contribute to the inhibition of the mycoparasite.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1159
TI  - Isolation and anticancer, anthelminthic, and antiviral (HIV) activity of acylphloroglucinols, and regioselective synthesis of empetrifranzinans from Hypericum roeperianum
JO  - Bioorg. Med. Chem.
PY  - 2015
SP  - 6327-6334
AU  - Tanemossu Fobofou, S. A.
AU  - Franke, K.
AU  - Sanna, G.
AU  - Porzel, A.
AU  - Bullita, E.
AU  - La Colla, P.
AU  - Wessjohann, L. A.
AU  - 
VL  - 23
UR  - 
DO  - 10.1016/j.bmc.2015.08.028
AB  - From the ethno-medicinally used leaves of Hypericum roeperianum we isolated a new tricyclic acylphloroglucinol (1), a new tetracyclic acylphloroglucinol (2), and a new prenylated bicyclic acylphloroglucinol (3) together with four known prenylated (4–7) and three known tetracyclic acylphloroglucinol derivatives (8–10). Structure elucidation was based on UV, IR, [α]D25, 1D- and 2D-NMR experiments. Furthermore, empetrifranzinans A (8) and C (9) were synthesized regioselectively in only two steps. The isolated compounds were evaluated for their cytotoxicity against PC-3 and HT-29 cancer cell lines as well as antibacterial and anthelmintic activities. They were also tested in cell-based assays for cytotoxicity against MT-4 cells and for anti-HIV activity in infected MT-4 cells. Significant anthelmintic activity against Caenorhabditis elegans was exhibited by compound 7 (3-geranyl-1-(2′-methylbutanoyl)-phloroglucinol), which might provide a new lead.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1157
TI  - Organoselenocyanates and symmetrical diselenides redox modulators: Design, synthesis and biological evaluation
JO  - Eur. J. Med. Chem.
PY  - 2015
SP  - 190-201
AU  - Shaaban, S.
AU  - Negm, A.
AU  - Sobh, M. A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 97
UR  - 
DO  - 10.1016/j.ejmech.2015.05.002
AB  - Oxidative stress (OS) and disturbed intracellular redox balance have been predominantly observed in different types of cancer, including hepatocellular carcinoma (HCC). Agents which can stop OS multi-stressor events and modulate the intracellular redox state are becoming a major focus in HCC prevention. Among them, compounds with glutathione peroxidase (GPx)-like activity are of particularly concern. We herein report the synthesis of novel series of organoselenocyanates and symmetrical diselenide antioxidants, inspired by the natural redox enzyme, GPx and the synthetic organoselenium ebselen antioxidants. Their cytotoxic activity was evaluated against Hep G2 cells and their antimicrobial activities were evaluated against Candida albicans (C. albicans) fungus as well as against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), gram-negative and gram-positive bacteria, respectively. These compounds were also tested for their antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), GPx-like activity and bleomycin dependent DNA damage assays and a basic structure–activity relationship was subsequently established. The physicochemical parameters and drug-likeness were computed employing the Molinspiration online property calculation toolkit and MolSoft software. Interestingly, some compounds proved to be more cytotoxic than ebselen and the known anticancer drug 5-Fu and in the same time they showed similar, sometime even more, antifungal activity than the reference antifungal drugs. Among these compounds, compound 16 was considered to be the most interesting with free radical-scavenging activity comparable to ascorbic acid and a GPx-like activity similar to ebselen. As most of these compounds comply with Lipinski&#39;s Rule of Five, they promise good bioavailability, which needs to be studied as part of future investigations.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1155
TI  - Diacetin, a reliable cue and private communication channel in a specialized pollination system
JO  - Sci. Rep.
PY  - 2015
SP  - 12779
AU  - Schäffler, I.
AU  - Steiner, K. E.
AU  - Haid, M.
AU  - van Berkel, S. S.
AU  - Gerlach, G.
AU  - Johnson, S. D.
AU  - Wessjohann, L.
AU  - Dötterl, S.
AU  - 
VL  - 5
UR  - 
DO  - 10.1038/srep12779
AB  - The interaction between floral oil secreting plants and oil-collecting bees is one of the most specialized of all pollination mutualisms. Yet, the specific stimuli used by the bees to locate their host flowers have remained elusive. This study identifies diacetin, a volatile acetylated glycerol, as a floral signal compound shared by unrelated oil plants from around the globe. Electrophysiological measurements of antennae and behavioural assays identified diacetin as the key volatile used by oil-collecting bees to locate their host flowers. Furthermore, electrophysiological measurements indicate that only oil-collecting bees are capable of detecting diacetin. The structural and obvious biosynthetic similarity between diacetin and associated floral oils make it a reliable cue for oil-collecting bees. It is easily perceived by oil bees, but can’t be detected by other potential pollinators. Therefore, diacetin represents the first demonstrated private communication channel in a pollination system.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1148
TI  - Bidirectional macrocyclization of peptides by double multicomponent reactions
JO  - Org. Biomol. Chem.
PY  - 2015
SP  - 438-446
AU  - Ricardo, M. G.
AU  - Morales, F. E.
AU  - Garay, H.
AU  - Reyes, O.
AU  - Vasilev, D.
AU  - Wessjohann, L. A.
AU  - Rivera, D. G.
AU  - 
VL  - 13
UR  - 
DO  - 10.1039/c4ob01915f
AB  - Increasing the diversity of peptide cyclization methods is an effective way of accessing new types of macrocyclic chemotypes featuring a wide variety of ring sizes and topologies. Multicomponent reactions (MCRs) are processes capable of generating great levels of molecular diversity and complexity at low synthetic cost. In an attempt to further exploit MCRs in the field of cyclopeptides, we describe a bidirectional multicomponent approach for the synthesis of N-alkylated macrocyclic peptides of varied sequences and cross-linking positions. The process relies on the execution of two Ugi reactions between peptide diacids and diisocyanides. Varying the amino component enabled the installation of exocyclic elements of diversity, while skeletal diversity was created through different side chain and backbone cyclizations. This procedure shows prospects for the rapid scanning of the chemical space of macrocyclic peptides for applications in chemical biology and drug discovery.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1143
TI  - Glandular β-glucosidases in juvenile Chrysomelina leaf beetles support the evolution of a host-plant-dependent chemical defense
JO  - Insect Biochem. Mol. Biol.
PY  - 2015
SP  - 28-38
AU  - Rahfeld, P.
AU  - Haeger, W.
AU  - Kirsch, R.
AU  - Pauls, G.
AU  - Becker, T.
AU  - Schulze, E.
AU  - Wielsch, N.
AU  - Wang, D.
AU  - Groth, M.
AU  - Brandt, W.
AU  - Boland, W.
AU  - Burse, A.
AU  - 
VL  - 58
UR  - 
DO  - 10.1016/j.ibmb.2015.01.003
AB  - Plant-feeding insects are spread across the entire plant kingdom. Because they chew externally on leaves, leaf beetle of the subtribe Chrysomelina sensu stricto are constantly exposed to life-threatening predators and parasitoids. To counter these pressures, the juveniles repel their enemies by displaying glandular secretions that contain defensive compounds. These repellents can be produced either de novo (iridoids) or by using plant-derived precursors. The autonomous production of iridoids pre-dates the evolution of phytochemical-based defense strategies. Both strategies include hydrolysis of the secreted non-toxic glycosides in the defensive exudates. By combining in vitro as well as in vivo experiments, we show that iridoid de novo producing as well as sequestering species rely on secreted β-glucosidases to cleave the pre-toxins. Our phylogenetic analyses support a common origin of chrysomeline β-glucosidases. The kinetic parameters of these β-glucosidases demonstrated substrate selectivity which reflects the adaptation of Chrysomelina sensu stricto to the chemistry of their hosts during the course of evolution. However, the functional studies also showed that the broad substrate selectivity allows building a chemical defense, which is dependent on the host plant, but does not lead to an “evolutionary dead end”.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1131
TI  - A fluorescence-based bioassay for antibacterials and its application in screening natural product extracts
JO  - J. Antibiot.
PY  - 2015
SP  - 734-740
AU  - Michels, K.
AU  - Heinke, R.
AU  - Schöne, P.
AU  - Kuipers, O. P.
AU  - Arnold, N.
AU  - Wessjohann, L. A.
AU  - 
VL  - 68
UR  - 
DO  - 10.1038/ja.2015.71
AB  - The reliable assessment of the biological activity of a minor component embedded in a complex matrix of several hundred compounds is a difficult but common task in the search for natural product-based antibiotics, for example, by bioassay-guided fractionation. To quantify the antibiotic properties, it is necessary to assess the cell viability. Direct measurements use CFU counts, OD measurements or detection via fluorescent or reducible dyes. However, natural extracts often already possess intrinsic dye, fluorescent, reducing or protein denaturing properties, or they contain insoluble compounds or general protein-binding (tanning) polyphenols as disturbing features, while at the same time very little of the selective antibiotic sought after is present. A promising alternative is provided by intrinsically produced bright fluorescent proteins. In this paper, a rapid, robust and concentration-dependent assay for screening antibiotics with genetically modified mutants of Bacillus subtilis 168 (PabrB-iyfp) is presented. The Gram-positive bacteria exhibit a native fluorescence during their exponential growth phase due to the expression of improved yellow fluorescent protein. To demonstrate the applicability in the field of natural product research, several compounds and extracts were screened for antibacterial activity, with an emphasis on those from the fungal genus Hygrophorus (waxy caps).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1129
TI  - Protease-inhibiting, molecular modeling and antimicrobial activities of extracts and constituents from Helichrysum foetidum and Helichrysum mechowianum (compositae)
JO  - Chem. Cent. J.
PY  - 2015
SP  - 32
AU  - Malolo, F.-A. E.
AU  - Bissoue Nouga, A.
AU  - Kakam, A.
AU  - Franke, K.
AU  - Ngah, L.
AU  - Flausino, O.
AU  - Mpondo Mpondo, E.
AU  - Ntie-Kang, F.
AU  - Ndom, J. C.
AU  - Bolzani, V. d. S.
AU  - Wessjohann, L.
AU  - 
VL  - 9
UR  - 
DO  - 10.1186/s13065-015-0108-1
AB  - BackgroundHelichrysum species are used extensively for stress-related ailments and as dressings for wounds normally encountered in circumcision rites, bruises, cuts and sores. It has been reported that Helichysum species are used to relief abdominal pain, heart burn, cough, cold, wounds, female sterility, menstrual pain.ResultsFrom the extracts of Helichrysum foetidum (L.) Moench, six known compounds were isolated and identified. They were 7, 4′-dihydroxy-5-methoxy-flavanone (1), 6′-methoxy-2′,4, 4′-trihydroxychalcone (2), 6′-methoxy-2′,4-dihydroxychalcone -4′-O-β-D-glucoside (3), apigenin (4), apigenin-7-O-β-D-glucoside (5), kaur-16-en-18-oic acid (6) while two known compounds 3,5,7-trihydroxy-8-methoxyflavone (12), 4,5-dicaffeoyl quinic acid (13) together with a mixture of phytosterol were isolated from the methanol extract of Helichrysum mechowianum Klatt. All the compounds were characterized by spectroscopic and mass spectrometric methods, and by comparison with literature data. Both extracts and all the isolates were screened for the protease inhibition, antibacterial and antifungal activities. In addition, the phytochemical profiles of both species were investigated by ESI-MS experiments.ConclusionsThese results showed that the protease inhibition assay of H. foetidum could be mainly attributed to the constituents of flavonoids glycosides (3, 5) while the compound (13) from H. mechowianum contributes to the stomach protecting effects. In addition, among the antibacterial and antifungal activities of all the isolates, compound (6) was found to possess a potent inhibitor effect against the tested microorganisms. The heterogeneity of the genus is also reflected in its phytochemical diversity. The differential bioactivities and determined constituents support the traditional use of the species. Molecular modelling was carried out by computing selected descriptors related to drug absorption, distribution, metabolism, excretion and toxicity (ADMET).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1127
TI  - Cm-p5: an antifungal hydrophilic peptide derived from the coastal mollusk Cenchritis muricatus (Gastropoda: Littorinidae)
JO  - FASEB J.
PY  - 2015
SP  - 3315-3325
AU  - López-Abarrategui, C.
AU  - McBeth, C.
AU  - Mandal, S. M.
AU  - Sun, Z. J.
AU  - Heffron, G.
AU  - Alba-Menéndez, A.
AU  - Migliolo, L.
AU  - Reyes-Acosta, O.
AU  - García-Villarino, M.
AU  - Nolasco, D. O.
AU  - Falcão, R.
AU  - Cherobim, M. D.
AU  - Dias, S. C.
AU  - Brandt, W.
AU  - Wessjohann, L.
AU  - Starnbach, M.
AU  - Franco, O. L.
AU  - Otero-González, A. J.
AU  - 
VL  - 29
UR  - 
DO  - 10.1096/fj.14-269860
AB  - Antimicrobial peptides form part of the first line of defense against pathogens for many organisms. Current treatments for fungal infections are limited by drug toxicity and pathogen resistance. Cm-p5 (SRSELIVHQRLF), a peptide derived from the marine mollusk Cenchritis muricatus peptide Cm-p1, has a significantly increased fungistatic activity against pathogenic Candida albicans (minimal inhibitory concentration, 10 µg/ml; EC50, 1.146 µg/ml) while exhibiting low toxic effects against a cultured mammalian cell line. Cm-p5 as characterized by circular dichroism and nuclear magnetic resonance revealed an α-helical structure in membrane-mimetic conditions and a tendency to random coil folding in aqueous solutions. Additional studies modeling Cm-p5 binding to a phosphatidylserine bilayer in silico and isothermal titration calorimetry using lipid monophases demonstrated that Cm-p5 has a high affinity for the phospholipids of fungal membranes (phosphatidylserine and phosphatidylethanolamine), only moderate interactions with a mammalian membrane phospholipid, low interaction with ergosterol, and no interaction with chitin. Adhesion of Cm-p5 to living C. albicans cells was confirmed by fluorescence microscopy with FITC-labeled peptide. In a systemic candidiasis model in mice, intraperitoneal administration of Cm-p5 was unable to control the fungal kidney burden, although its low amphiphaticity could be modified to generate new derivatives with improved fungicidal activity and stability.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1124
TI  - Emerging approaches for the synthesis of triazoles: beyond metal-catalyzed and strain-promoted azide–alkyne cycloaddition
JO  - Chem. Commun.
PY  - 2015
SP  - 10784-10796
AU  - Lima, C. G. S.
AU  - Ali, A.
AU  - van Berkel, S. S.
AU  - Westermann, B.
AU  - Paixão, M. W.
AU  - 
VL  - 51
UR  - 
DO  - 10.1039/c5cc04114g
AB  - Metal-free 1,3-dipolar cycloaddition reactions have proven to be a powerful tool for the assembly of key heterocycles, in particular diversely functionalized 1,2,3-triazoles. A number of metal-free (3+2)-cycloaddition approaches have been developed up to date with the aim to circumvent the use of metal catalysts allowing these reactions to take place in biological systems without perturbation of the naturally occurring processes. This feature article specifically provides an overview of emerging metal-free synthetic routes, and their mechanistic features, in the formation of functionalized 1,2,3-triazoles.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1141
TI  - In vitro anticancer activity of gold(III) complexes with some esters of (S,S)-ethylenediamine-N,N′-di-2-propanoic acid
JO  - Eur. J. Med. Chem.
PY  - 2015
SP  - 766-774
AU  - Pantelić, N.
AU  - Stanojković, T. P.
AU  - Zmejkovski, B. B.
AU  - Sabo, T. J.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 90
UR  - 
DO  - 10.1016/j.ejmech.2014.12.019
AB  - Five novel gold(III) complexes of general formulas [AuCl2{(S,S)-R2eddip}]PF6, ((S,S)-eddip = (S,S)-ethylenediamine-N,N′-di-2-propanoate, R = n-Bu, n-Pe, i-Bu, i-Am, cPe; 1–5, respectively) were synthesized and characterized by UV/Vis, IR and NMR spectroscopy and mass spectrometry. DFT calculations indicated that (R,R)-N,N′-configuration diastereoisomers were the most stable for 1–5. 3 is stable in DMSO for at least 24 h, but immediate hydrolysis in PBS occurs. 3 is readily reduced with ascorbic acid and forms adducts with bovine serum albumin (BSA). In vitro anticancer activity of the gold(III) complexes against human cervix adenocarcinoma HeLa, human myelogenous leukemia K562, human melanoma Fem-x tumor cell lines, as well as against non-cancerous human embryonic lung fibroblast cell line MRC-5 was determined using MTT assay. Complex 4 showed highest activity and selectivity (IC50(Fem-x) = 1.3 ± 0.2; IC50(MRC-5)/IC50(Fem-x) = 72.5 ± 12.4), 4 times more active and 28 times more selective than cisplatin. Complexes induced apoptotic mode of death in a time-dependent manner in HeLa cells.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1140
TI  - Isolation and Total Synthesis of Albu­peptins A-D: 11-Residue Peptaibols from the Fungus Gliocladium album
JO  - Eur. J. Org. Chem.
PY  - 2015
SP  - 7449-7459
AU  - Otto, A.
AU  - Laub, A.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Wessjohann, L.
AU  - Westermann, B.
AU  - Arnold, N.
AU  - 
VL  - 2015
UR  - 
DO  - 10.1002/ejoc.201501124
AB  - Four new 11‐mer peptaibols, named albupeptins A–D (1–4), were isolated from cultures of the fungus Gliocladium album. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopy, as well as ESI‐HRMSn analysis. The sequence of albupeptin A (1) was thus identified as Ac‐Aib1‐Aib2‐Val3‐Leu4‐Aib5‐Pro6‐Iva7‐Leu8‐Gln9‐Aib10‐Leuol11. Albupeptins B (2) and C (3) feature an exchange of Aib5 by Iva5 and of Aib1 by Iva1, respectively, and albupeptin D (4) contains both Iva1 and Iva5 residues. The stereochemistry of the isolated peptaibols 1–4 was unambiguously assigned by 1H NMR chemical shift analysis in conjunction with solid‐phase peptide synthesis. By using this approach, the absolute configuration of the Iva residues in albupeptins A (1) and C (3) was determined to be D, whereas albupeptins B (2) and D (4) feature an additional Iva5 residue with an L configuration. Thus, albupeptins B (2) and D (4) belong to the rare class of peptaibols that have both stereoisomers of Iva in the same sequence.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1139
TI  - A study on the biosynthesis of hygrophorone B12 in the mushroom Hygrophorus abieticola reveals an unexpected labelling pattern in the cyclopentenone moiety
JO  - Phytochemistry
PY  - 2015
SP  - 174-180
AU  - Otto, A.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Wessjohann, L.
AU  - Arnold, N.
AU  - 
VL  - 118
UR  - 
DO  - 10.1016/j.phytochem.2015.08.018
AB  - The hitherto unknown natural formation of hygrophorones, antibacterial and antifungal cyclopentenone derivatives from mushrooms, was investigated for hygrophorone B12 in Hygrophorus abieticola Krieglst. ex Gröger &amp; Bresinsky by feeding experiments in the field using 13C labelled samples of d-glucose and sodium acetate. The incorporation of 13C isotopes was extensively studied using 1D and 2D NMR spectroscopy as well as ESI-HRMS analyses. In the experiment with [U-13C6]-glucose, six different 13C2 labelled isotopomers were observed in the 2D INADEQUATE spectrum due to incorporation of [1,2-13C2]-acetyl-CoA. This labelling pattern demonstrated that hygrophorone B12 is derived from a fatty acid-polyketide route instead of a 1,4-α-d-glucan derived anhydrofructose pathway. The experiment with [2-13C]-acetate revealed an unexpected incorporation pattern in the cyclopentenone functionality of hygrophorone B12. Four single-labelled isotopomers, in particular [1-13C]-, [2-13C]-, [3-13C]-, and [4-13C]-hygrophorone B12, were detected that showed only half enrichment in comparison to the respective labelled alkyl side chain carbons. This labelling pattern indicates the formation of a symmetrical intermediate during hygrophorone B12 biosynthesis. Based on these observations, a biogenetic route via a 4-oxo fatty acid and a chrysotrione B homologue is discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1137
TI  - Arabidopsis thaliana isoprenyl diphosphate synthases produce the C25 intermediate geranylfarnesyl diphosphate
JO  - Plant J.
PY  - 2015
SP  - 847-859
AU  - Nagel, R.
AU  - Bernholz, C.
AU  - Vranová, E.
AU  - Košuth, J.
AU  - Bergau, N.
AU  - Ludwig, S.
AU  - Wessjohann, L.
AU  - Gershenzon, J.
AU  - Tissier, A.
AU  - Schmidt, A.
AU  - 
VL  - 84
UR  - 
DO  - 10.1111/tpj.13064
AB  - Isoprenyl diphosphate synthases (IDSs) catalyze some of the most basic steps in terpene biosynthesis by producing the prenyl diphosphate precursors of each of the various terpenoid classes. Most plants investigated have distinct enzymes that produce the short‐chain all‐trans (E) prenyl diphosphates geranyl diphosphate (GDP, C10), farnesyl diphosphate (FDP, C15) or geranylgeranyl diphosphate (GGDP, C20). In the genome of Arabidopsis thaliana, 15 trans‐product‐forming IDSs are present. Ten of these have recently been shown to produce GGDP by genetic complementation of a carotenoid pathway engineered into Escherichia coli. When verifying the product pattern of IDSs producing GGDP by a new LC‐MS/MS procedure, we found that five of these IDSs produce geranylfarnesyl diphosphate (GFDP, C25) instead of GGDP as their major product in enzyme assays performed in vitro. Over‐expression of one of the GFDP synthases in A. thaliana confirmed the production of GFDP in vivo. Enzyme assays with A. thaliana protein extracts from roots but not other organs showed formation of GFDP. Furthermore, GFDP itself was detected in root extracts. Subcellular localization studies in leaves indicated that four of the GFDP synthases were targeted to the plastoglobules of the chloroplast and one was targeted to the mitochondria. Sequence comparison and mutational studies showed that the size of the R group of the 5th amino acid residue N‐terminal to the first aspartate‐rich motif is responsible for C25 versus C20 product formation, with smaller R groups (Ala and Ser) resulting in GGDP (C20) as a product and a larger R group (Met) resulting in GFDP (C25).
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1088
TI  - Rationally engineered variants of S-adenosylmethionine (SAM) synthase: reduced product inhibition and synthesis of artificial cofactor homologues
JO  - Chem. Commun.
PY  - 2015
SP  - 3637-3640
AU  - Dippe, M.
AU  - Brandt, W.
AU  - Rost, H.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Wessjohann, L. A.
AU  - 
VL  - 51
UR  - 
DO  - 10.1039/c4cc08478k
AB  - S-Adenosylmethionine (SAM) synthase was engineered for biocatalytic production of SAM and long-chain analogues by rational re-design. Substitution of two conserved isoleucine residues extended the substrate spectrum of the enzyme to artificial S-alkylhomocysteines. The variants proved to be beneficial in preparative synthesis of SAM (and analogues) due to a much reduced product inhibition.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1085
TI  - Improved in vitro antitumor potential of (O,O′-Diisobutyl-ethylenediamine-N,N′-di-3-propionate)tetrachloridoplatinum(IV) complex under normoxic and hypoxic conditions
JO  - Eur. J. Pharmacol.
PY  - 2015
SP  - 136-144
AU  - Bulatović, M.
AU  - Kaluđerović, M. R.
AU  - Mojić, M.
AU  - Zmejkovski, B. B.
AU  - Hey-Hawkins, E.
AU  - Vidaković, M.
AU  - Grdović, N.
AU  - Kaluđerović, G. N.
AU  - Mijatović, S.
AU  - Maksimović-Ivanić, D.
AU  - 
VL  - 760
UR  - 
DO  - 10.1016/j.ejphar.2015.04.012
AB  - (O,O′-Diisobutyl-ethylenediamine-N,N′-di-3-propionate)tetrachloridoplatinum(IV), [PtCl4(iBu2eddp)], shows an improved pharmacological profile in comparison to cisplatin. This is manifested through accelerated dying process led by necrotic cell death, reflected through mitochondrial collapse, strong ATP depletion and reactive oxygen species production. Loss of mitochondrial potential was further followed with intensive apoptosis that finalized with DNA fragmentation.Different dynamic of tumoricidal action could be partly ascribed to less affected repair mechanisms in comparison to cisplatin. Importantly, [PtCl4(iBu2eddp)] did not induce necrosis in primary fibroblasts suggesting different intracellular response of normal vs. tumor cells. This selectivity toward malignant phenotype is further confirmed by retained tumoricidal potential in hypoxic conditions, while cisplatin became completely inefficient.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1083
TI  - Methylated derivatives of myricetin enhance life span in Caenorhabditis elegans dependent on the transcription factor DAF-16
JO  - Food Funct.
PY  - 2015
SP  - 3383-3392
AU  - Büchter, C.
AU  - Ackermann, D.
AU  - Honnen, S.
AU  - Arnold, N.
AU  - Havermann, S.
AU  - Koch, K.
AU  - Wätjen, W.
AU  - 
VL  - 6
UR  - 
DO  - 10.1039/c5fo00463b
AB  - Only certain flavonoids have been shown to enhance life span. This was pointed out for e.g. myricetin in the nematode Caenorhabditis elegans. However, the structural requirements responsible for this effect are not known. We used methylated derivatives of myricetin (laricitrin, syringetin, myricetintrimethylether) to investigate if free OH moieties in the B-ring are necessary for the life span extending effect. In analogy to myricetin, all derivatives increased the life span, decreased oxidative stress (DCF) and decreased the accumulation of lipofuscin. In contrast to myricetin, the methylated compounds strongly enhanced the resistance against thermal stress. Furthermore, treatment with the derivatives induced a much stronger nuclear localization of the DAF-16 transcription factor (FoxO homologue). Additionally, no antioxidant effects and only minor effects on life span prolongation and stress resistance were detectable for the methylated compounds in a DAF-16 deficient nematode strain. Comparable to the dietary flavonoid myricetin, the methylated myricetin derivatives laricitrin, syringetin and myricetintrimethylether strongly enhance the life span of C. elegans. Therefore, OH groups of ring B are not necessary for this effect. Only the methylated compounds increase the stress resistance of the nematode which was dependent on DAF-16. These findings suggest that methylation of myricetin increases the biofunctionality.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1081
TI  - Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach
JO  - Beilstein J. Org. Chem.
PY  - 2015
SP  - 25-30
AU  - Brauer, M. C. N.
AU  - Neves Filho, R. A. W.
AU  - Westermann, B.
AU  - Heinke, R.
AU  - Wessjohann, L. A.
AU  - 
VL  - 11
UR  - 
DO  - 10.3762/bjoc.11.4
AB  - A library of ten 1,3-diyne-linked peptoids has been synthesized through an Ugi four-component reaction (U-4CR) followed by a copper-catalysed alkyne homocoupling (Glaser reaction). The short and chemoselective reaction sequence allows generating diverse (pseudo) dimeric peptoids. A combinatorial version allows the one-pot preparation of, e.g., six-compound-libraries of homo- and heterodimers verified by ESI-MS and HPLC. In a preliminary evaluation, some compounds display moderate activity against the Gram-positive bacterium Bacillus subtilis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1080
TI  - A catalytic triad – Lys-Asn-Asp – Is essential for the catalysis of the methyl transfer in plant cation-dependent O-methyltransferases
JO  - Phytochemistry
PY  - 2015
SP  - 130-139
AU  - Brandt, W.
AU  - Manke, K.
AU  - Vogt, T.
AU  - 
VL  - 113
UR  - 
DO  - 10.1016/j.phytochem.2014.12.018
AB  - Crystal structure data of cation-dependent catechol O-methyltransferases (COMTs) from mammals and related caffeoyl coenzyme A OMTs (CCoAOMTs) from plants have suggested operative molecular mechanisms. These include bivalent cations that facilitate deprotonation of vicinal aromatic dihydroxy systems and illustrate a conserved arrangement of hydroxyl and carboxyl ligands consistent with the requirements of a metal-activated catalytic mechanism. The general concept of metal-dependent deprotonation via a complexed aspartate is only one part of a more pronounced proton relay, as shown by semiempirical and DFT quantum mechanical calculations and experimental validations. A previously undetected catalytic triad, consisting of Lys157-Asn181-Asp228 residues is required for complete methyl transfer in case of a cation-dependent phenylpropanoid and flavonoid OMT, as described in this report. This triad appears essential for efficient methyl transfer to catechol-like hydroxyl group in phenolics. The observation is consistent with a catalytic lysine in the case of mammalian COMTs, but jettisons existing assumptions on the initial abstraction of the meta-hydroxyl proton to the metal stabilizing Asp154 (PFOMT) or comparable Asp-carboxyl groups in type of cation-dependent enzymes in plants. The triad is conserved among all characterized plant CCoAOMT-like enzymes, which are required not only for methylation of soluble phenylpropanoids like coumarins or monolignol monomers, but is also present in the similar microbial and mammalian cation-dependent enzymes which methylate a comparable set of substrates.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1076
TI  - Screening of synthetic and natural product databases: Identification of novel androgens and antiandrogens
JO  - Eur. J. Med. Chem.
PY  - 2015
SP  - 267-279
AU  - Bobach, C.
AU  - Tennstedt, S.
AU  - Palberg, K.
AU  - Denkert, A.
AU  - Brandt, W.
AU  - de Meijere, A.
AU  - Seliger, B.
AU  - Wessjohann, L. A.
AU  - 
VL  - 90
UR  - 
DO  - 10.1016/j.ejmech.2014.11.026
AB  - The androgen receptor is an important pharmaceutical target for a variety of diseases. This paper presents an in silico/in vitro screening procedure to identify new androgen receptor ligands. The two-step virtual screening procedure uses a three-dimensional pharmacophore model and a docking/scoring routine. About 39,000 filtered compounds were docked with PLANTS and scored by Chemplp. Subsequent to virtual screening, 94 compounds, including 28 steroidal and 66 nonsteroidal compounds, were tested by an androgen receptor fluorescence polarization ligand displacement assay. As a result, 30 compounds were identified that show a relative binding affinity of more than 50% in comparison to 100 nM dihydrotestosterone and were classified as androgen receptor binders. For 11 androgen receptor binders of interest IC50 and Ki values were determined. The compound with the highest affinity exhibits a Ki value of 10.8 nM. Subsequent testing of the 11 compounds in a PC-3 and LNCaP multi readout proliferation assay provides insights into the potential mode of action. Further steroid receptor ligand displacement assays and docking studies on estrogen receptors α and β, glucocorticoid receptor, and progesterone receptor gave information about the specificity of the 11 most active compounds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1075
TI  - Lemairones A and B: Two new antibacterial tetraflavonoids from the leaves of Zanthoxylum lemairei (Rutaceae)
JO  - Phytochem. Lett.
PY  - 2015
SP  - 1-7
AU  - Bitchagno, G. T. M.
AU  - Tankeo, S. B.
AU  - Tsopmo, A.
AU  - Mpetga, J. D. S.
AU  - Tchinda, A. T.
AU  - Fobofou, S. A. T.
AU  - Wessjohann, L. A.
AU  - Kuete, V.
AU  - Tane, P.
AU  - 
VL  - 14
UR  - 
DO  - 10.1016/j.phytol.2015.08.012
AB  - Zanthoxylum lemairei is widely used in African folk medicine for its pharmacological relevance. Chemical investigation of the ethanol extract from the leaves of this plant lead to the isolation of two new tetraflavonoids, lemairones A (1) and B (2), along with three known compounds, lupeol, sitosterol, and sitosterol 3-O-β-d-glucopyranoside. The antibacterial screening of the leaves of this plant, characterization of compounds 1 and 2, and their antibacterial activity are reported for the first time. The isolation of the compounds was performed using different chromatographic methods while their structures were elucidated by spectroscopic techniques including MS and NMR, and by comparison of data with those of similar flavonoids reported in the literature. The isolated compounds and the crude extract were tested against ten Gram negative multi-resistance bacterial strains including clinical isolates using a broth dilution method. The crude ethanol extract showed weak activity against the tested bacteria strains with a minimal inhibitory concentration (MIC) ranging from 512 to 1024 μg/mL. Among the isolated metabolites, only the new tetraflavonoids were tested. Lemairone A displayed weak activity while lemairone B had moderate activity against the resistant Escherichia coli AG100 with MIC values of 128 μg/mL and 64 μg/mL respectively. In addition, both molecules displayed weak activity against Klebsiella pneumoniae KP55 (MIC 128 μg/mL).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1074
TI  - Isolation and Asymmetric Total Synthesis of Fungal Secondary Metabolite Hygrophorone B12
JO  - Eur. J. Org. Chem.
PY  - 2015
SP  - 2357-2365
AU  - Bette, E.
AU  - Otto, A.
AU  - Dräger, T.
AU  - Merzweiler, K.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - Westermann, B.
AU  - 
VL  - 2015
UR  - 
DO  - 10.1002/ejoc.201403455
AB  - Hygrophorone B12, a new antifungal constituent from the fruiting bodies of Hygrophorus abieticola, has been isolated and subsquently synthesized in enantiomerically pure form. The total synthesis includes a Sharpless asymmetric dihydroxylation protocol as the stereodifferentiating step, followed by two diastereoselective aldol‐type reactions. The approach allows the unambiguous control of all three stereogenic centres, and, furthermore, unequivocal determination of the relative and absolute configuration of antibiotic hygrophorones B for the first time.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1072
TI  - Correction: Synthesis, cytotoxic and hydrolytic studies of titanium complexes anchored by a tripodal diamine bis(phenolate) ligand
JO  - Dalton Trans.
PY  - 2015
SP  - 2497-2497
AU  - Barroso, S.
AU  - Coelho, A. M.
AU  - Gómez-Ruiz, S.
AU  - Calhorda, M. J.
AU  - Žižak, ?.
AU  - Kaluđerović, G. N.
AU  - Martins, A. M.
AU  - 
VL  - 44
UR  - 
DO  - 10.1039/C4DT90194K
AB  - Correction for ‘Synthesis, cytotoxic and hydrolytic studies of titanium complexes anchored by a tripodal diamine bis(phenolate) ligand’ by Sónia Barroso et al., Dalton Trans., 2014, 43, 17422–17433.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1071
TI  - Perfusion Single Photon Emission Computed Tomography in a Mouse Model of Neurofibromatosis Type 1: Towards a Biomarker of Neurologic Deficits
JO  - J. Cereb. Blood Flow Metab.
PY  - 2015
SP  - 1304-1312
AU  - Apostolova, I.
AU  - Niedzielska, D.
AU  - Derlin, T.
AU  - Koziolek, E. J.
AU  - Amthauer, H.
AU  - Salmen, B.
AU  - Pahnke, J.
AU  - Brenner, W.
AU  - Mautner, V. F.
AU  - Buchert, R.
AU  - 
VL  - 35
UR  - 
DO  - 10.1038/jcbfm.2015.43
AB  - Neurofibromatosis type 1 (NF1) is a single-gene disorder affecting neurologic function in humans. The NF1+/– mouse model with germline mutation of the NF1 gene presents with deficits in learning, attention, and motor coordination, very similar to NF1 patients. The present study performed brain perfusion single-photon emission computed tomography (SPECT) in NF1+/– mice to identify possible perfusion differences as surrogate marker for altered cerebral activity in NF1. Cerebral perfusion was measured with hexamethyl-propyleneamine oxime (HMPAO) SPECT in NF1+/– mice and their wild-type littermates longitudinally at juvenile age and at young adulthood. Histology and immunohistochemistry were performed to test for structural changes. There was increased HMPAO uptake in NF1 mice in the amygdala at juvenile age, which reduced to normal levels at young adulthood. There was no genotype effect on thalamic HMPAO uptake, which was confirmed by ex vivo measurements of F-18-fluorodeoxyglucose uptake in the thalamus. Morphologic analyses showed no major structural abnormalities. However, there was some evidence of increased density of microglial somata in the amygdala of NF1-deficient mice. In conclusion, there is evidence of increased perfusion and increased density of microglia in juvenile NF1 mice specifically in the amygdala, both of which might be associated with altered synaptic plasticity and, therefore, with cognitive deficits in NF1.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1123
TI  - Correction: Emerging approaches for the synthesis of triazoles: beyond metal-catalyzed and strain-promoted azide–alkyne cycloaddition
JO  - Chem. Commun.
PY  - 2015
SP  - 12139-12139
AU  - Lima, C. G. S.
AU  - Ali, A.
AU  - van Berkel, S. S.
AU  - Westermann, B.
AU  - Paixão, M. W.
AU  - 
VL  - 51
UR  - 
DO  - 10.1039/C5CC90314A
AB  - Correction for &#39;Emerging approaches for the synthesis of triazoles: beyond metal-catalyzed and strain-promoted azide–alkyne cycloaddition&#39; by Carolina G. S. Lima et al., Chem. Commun., 2015, 51, 10784–10796.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1121
TI  - Hydrogen peroxide – production, fate and role in redox signaling of tumor cells
JO  - Cell Commun. Signal.
PY  - 2015
SP  - 
AU  - Lennicke, C.
AU  - Rahn, J.
AU  - Lichtenfels, R.
AU  - Wessjohann, L. A.
AU  - Seliger, B.
AU  - 
VL  - 13
UR  - 
DO  - 10.1186/s12964-015-0118-6
AB  - Hydrogen peroxide (H2O2) is involved in various signal transduction pathways and cell fate decisions. The mechanism of the so called “redox signaling” includes the H2O2-mediated reversible oxidation of redox sensitive cysteine residues in enzymes and transcription factors thereby altering their activities. Depending on its intracellular concentration and localization, H2O2 exhibits either pro- or anti-apoptotic activities. In comparison to normal cells, cancer cells are characterized by an increased H2O2 production rate and an impaired redox balance thereby affecting the microenvironment as well as the anti-tumoral immune response. This article reviews the current knowledge about the intracellular production of H2O2 along with redox signaling pathways mediating either the growth or apoptosis of tumor cells. In addition it will be discussed how the targeting of H2O2-linked sources and/or signaling components involved in tumor progression and survival might lead to novel therapeutic targets.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1117
TI  - Accumulation of murine amyloid-β mimics early Alzheimer’s disease
JO  - Brain
PY  - 2015
SP  - 2370-2382
AU  - Krohn, M.
AU  - Bracke, A.
AU  - Avchalumov, Y.
AU  - Schumacher, T.
AU  - Hofrichter, J.
AU  - Paarmann, K.
AU  - Fröhlich, C.
AU  - Lange, C.
AU  - Brüning, T.
AU  - von Bohlen und Halbach, O.
AU  - Pahnke, J.
AU  - 
VL  - 138
UR  - 
DO  - 10.1093/brain/awv137
AB  - Amyloidosis mouse models of Alzheimer’s disease are generally established by transgenic approaches leading to an overexpression of mutated human genes that are known to be involved in the generation of amyloid-β in Alzheimer’s families. Although these models made substantial contributions to the current knowledge about the ‘amyloid hypothesis’ of Alzheimer’s disease, the overproduction of amyloid-β peptides mimics only inherited (familiar) Alzheimer’s disease, which accounts for &lt;1% of all patients with Alzheimer’s disease. The inherited form is even regarded a ‘rare’ disease according to the regulations for funding of the European Union (www.erare.eu). Here, we show that mice that are double-deficient for neprilysin (encoded by Mme), one major amyloid-β-degrading enzyme, and the ABC transporter ABCC1, a major contributor to amyloid-β clearance from the brain, develop various aspects of sporadic Alzheimer’s disease mimicking the clinical stage of mild cognitive impairment. Using behavioural tests, electrophysiology and morphological analyses, we compared different ABC transporter-deficient animals and found that alterations are most prominent in neprilysin × ABCC1 double-deficient mice. We show that these mice have a reduced probability to survive, show increased anxiety in new environments, and have a reduced working memory performance. Furthermore, we detected morphological changes in the hippocampus and amygdala, e.g. astrogliosis and reduced numbers of synapses, leading to defective long-term potentiation in functional measurements. Compared to human, murine amyloid-β is poorly aggregating, due to changes in three amino acids at N-terminal positions 5, 10, and 13. Interestingly, our findings account for the action of early occurring amyloid-β species/aggregates, i.e. monomers and small amyloid-β oligomers. Thus, neprilysin × ABCC1 double-deficient mice present a new model for early effects of amyloid-β-related mild cognitive impairment that allows investigations without artificial overexpression of inherited Alzheimer’s disease genes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1116
TI  - Microalgae as source for potential anti-alzheimer´s disease directed compounds - screening for glutaminyl cyclase (QC) inhibiting matabolites
JO  - Int. J. Pharm. Biol. Sci.
PY  - 2015
SP  - 164-170
AU  - Krause-Hielscher, S.
AU  - Demuth, H.-U.
AU  - Wessjohann, L.
AU  - Arnold, N.
AU  - Griehl, C.
AU  - 
VL  - 5
UR  - https://www.ijpbs.com/previousissue.php?year=2015&amp;issue=4&amp;page=2
AB  - Alzheimer´s disease (AD) is the most common form of dementia affecting predominantly elderly people from developed countries. One aspect of the illness is that patients suffer from an impaired memory due to deposition of aggregated A-peptides forming amyloid plaques. According to the glutaminyl cyclase (QC) hypothesis this enzyme plays a key role in generating neurotoxic amyloid peptides (amyloid-β or Aβ) by modifying the N-terminus of peptides to N-pyroglutamated derivatives. These modified proteins are resistant to degradation and are at the same time “seeds” for the formation of toxic A-oligomers in the brain. In order to screen for natural inhibitors of QC, strains of different species of algae belonging to Chlorophyceae and Eustigmatophyceae were cultivated in 100 L tubular photobioreactors. The resulting crude extracts of algae from exponential and stationary growth phases were tested for their inhibition properties of glutaminyl cyclase (QC). Here 27 of the 72 tested extracts inhibited the QC. Fractions separated by Sephadex G-15 column chromatography also showed QC inhibition activity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1113
TI  - Studies on the Biotransformation of Veratric Acid, a Human Metabolite of Mebeverine, by Using the Incubated Hen’s Egg
JO  - Drug Res.
PY  - 2015
SP  - 500-504
AU  - Kiep, L.
AU  - Göhl, M.
AU  - Schmidt, J.
AU  - Seifert, K.
AU  - 
VL  - 65
UR  - 
DO  - 10.1055/s-0034-1390457
AB  - Metabolism studies with selected test substances have shown that a model on the basis of the incubated hen’s egg is suitable as a supplement to animal experimentation. Because of its 3,4-dimethoxyphenyl structure veratric acid (3,4-dimethoxybenzoic acid), a known human metabolite of mebeverine, was chosen as model substance for the present investigations and the parent compound as well as 4-hydroxy-3-methoxybenzoic acid were identified as main metabolites. The absence of 3-hydroxy-4-methoxybenzoic acid lets conclude that the O-demethylation takes place exclusively at the p-methoxyl function. In addition, 3,3’,4,4’-tetramethoxy-l-ornithuric acid (2,5-bis-(3,4-dimethoxybenzoylamino)pentanoic acid) and its O-desmethyl derivative could be characterized as further metabolites. So far an amino acid conjugate has not been described after veratric acid administration in a vertebrate. There were no indications for the appearance of 3,4-dihydroxybenzoic acid in the veratric acid metabolism. This was confirmed by corresponding studies having the isomeric guaiacol acids as precursor. Furthermore, it could be proved that in ovo the O-methylation of 3,4-dihydroxybenzoic acid occurs regioselective at the m-hydroxyl group. The results which broaden the knowledge on the metabolic fate of veratric acid are discussed in comparison with those in mammals. The metabolites were identified by GC-MS, ESI-HRMS and LC/ESI-MS/MS. The structure of the synthesized reference substance was confirmed by MS, 1H and 13C NMR spectral data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1112
TI  - O-Methyltransferases involved in biphenyl and dibenzofuran biosynthesis
JO  - Plant J.
PY  - 2015
SP  - 263-276
AU  - Khalil, M. N.
AU  - Brandt, W.
AU  - Beuerle, T.
AU  - Reckwell, D.
AU  - Groeneveld, J.
AU  - Hänsch, R.
AU  - Gaid, M. M.
AU  - Liu, B.
AU  - Beerhues, L.
AU  - 
VL  - 83
UR  - 
DO  - 10.1111/tpj.12885
AB  - Biphenyls and dibenzofurans are the phytoalexins of the Malinae involving apple and pear. Biosynthesis of the defence compounds includes two O‐methylation reactions. cDNAs encoding the O‐methyltransferase (OMT) enzymes were isolated from rowan (Sorbus aucuparia) cell cultures after treatment with an elicitor preparation from the scab‐causing fungus, Venturia inaequalis. The preferred substrate for SaOMT1 was 3,5‐dihydroxybiphenyl, supplied by the first pathway‐specific enzyme, biphenyl synthase (BIS). 3,5‐Dihydroxybiphenyl underwent a single methylation reaction in the presence of S‐adenosyl‐l‐methionine (SAM). The second enzyme, SaOMT2, exhibited its highest affinity for noraucuparin, however the turnover rate was greater with 5‐hydroxyferulic acid. Both substrates were only methylated at the meta‐positioned hydroxyl group. The substrate specificities of the OMTs and the regiospecificities of their reactions were rationalized by homology modeling and substrate docking. Interaction of the substrates with SAM also took place at a position other than the sulfur group. Expression of SaOMT1, SaOMT2 and SaBIS3 was transiently induced in rowan cell cultures by the addition of the fungal elicitor. While the immediate SaOMT1 products were not detectable in elicitor‐treated cell cultures, noraucuparin and noreriobofuran accumulated transiently, followed by increasing levels of the SaOMT2 products aucuparin and eriobofuran. SaOMT1, SaOMT2 and SaBIS3 were N‐ and C‐terminally fused with the super cyan fluorescent protein and a modified yellow fluorescent protein, respectively. All the fluorescent reporter fusions were localized to the cytoplasm of Nicotiana benthamiana leaf epidermis cells. A revised biosynthetic pathway of biphenyls and dibenzofurans in the Malinae is presented.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1111
TI  - Ruthenium(II) p-cymene complex bearing 2,2′-dipyridylamine targets caspase 3 deficient MCF-7 breast cancer cells without disruption of antitumor immune response
JO  - J. Inorg. Biochem.
PY  - 2015
SP  - 315-321
AU  - Kaluđerović, G. N.
AU  - Krajnović, T.
AU  - Momčilović, M.
AU  - Stosic-Grujicic, S.
AU  - Mijatović, S.
AU  - Maksimović-Ivanić, D.
AU  - Hey-Hawkins, E.
AU  - 
VL  - 153
UR  - 
DO  - 10.1016/j.jinorgbio.2015.09.006
AB  - [Ru(η6-p-cym)Cl{dpa(CH2)4COOEt}][PF6] (cym = cymene; dpa = 2,2′-dipyridylamine; complex 2) was prepared and characterized by elemental analysis, IR and multinuclear NMR spectroscopy, as well as ESI-MS and X-ray structural analysis. The structural analog without a side chain [Ru(η6-p-cym)Cl(dpa)][PF6] (1) as well as 2 were investigated in vitro against 518A2, SW480, 8505C, A253 and MCF-7 cell lines. Complex 1 is active against all investigated tumor cell lines while the activity of compound 2 is limited only to caspase 3 deficient MCF-7 breast cancer cells, however, both are less active than cisplatin. As CD4+ Th cells are necessary to trigger all the immune effector mechanisms required to eliminate tumor cells, besides testing the in vitro antitumor activity of 1 and 2, the effect of ruthenium(II) complexes on the cells of the adaptive immune system have also been evaluated. Importantly, complex 1 applied in concentrations which were effective against tumor cells did not affect immune cell viability, nor did exert a general immunosuppressive effect on cytokine production. Thus, beneficial characteristics of 1 might contribute to the overall therapeutic properties of the complex.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1110
TI  - “Self” and “Non-Self” in the Control of Phytoalexin Biosynthesis: Plant Phospholipases A2 with Alkaloid-Specific Molecular Fingerprints
JO  - Plant Cell
PY  - 2015
SP  - 448-462
AU  - Heinze, M.
AU  - Brandt, W.
AU  - Marillonnet, S.
AU  - Roos, W.
AU  - 
VL  - 27
UR  - 
DO  - 10.1105/tpc.114.135343
AB  - The overproduction of specialized metabolites requires plants to manage the inherent burdens, including the risk of self-intoxication. We present a control mechanism that stops the expression of phytoalexin biosynthetic enzymes by blocking the antecedent signal transduction cascade. Cultured cells of Eschscholzia californica (Papaveraceae) and Catharanthus roseus (Apocynaceae) overproduce benzophenanthridine alkaloids and monoterpenoid indole alkaloids, respectively, in response to microbial elicitors. In both plants, an elicitor-responsive phospholipase A2 (PLA2) at the plasma membrane generates signal molecules that initiate the induction of biosynthetic enzymes. The final alkaloids produced in the respective plant inhibit the respective PLA, a negative feedback that prevents continuous overexpression. The selective inhibition by alkaloids from the class produced in the “self” plant could be transferred to leaves of Nicotiana benthamiana via recombinant expression of PLA2. The 3D homology model of each PLA2 displays a binding pocket that specifically accommodates alkaloids of the class produced by the same plant, but not of the other class; for example, C. roseus PLA2 only accommodates C. roseus alkaloids. The interaction energies of docked alkaloids correlate with their selective inhibition of PLA2 activity. The existence in two evolutionary distant plants of phospholipases A2 that discriminate “self-made” from “foreign” alkaloids reveals molecular fingerprints left in signal enzymes during the evolution of species-specific, cytotoxic phytoalexins.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1106
TI  - The crystal structure of the thiocyanate-forming protein from Thlaspi arvense, a kelch protein involved in glucosinolate breakdown
JO  - Plant Mol. Biol.
PY  - 2015
SP  - 67-81
AU  - Gumz, F.
AU  - Krausze, J.
AU  - Eisenschmidt, D.
AU  - Backenköhler, A.
AU  - Barleben, L.
AU  - Brandt, W.
AU  - Wittstock, U.
AU  - 
VL  - 89
UR  - 
DO  - 10.1007/s11103-015-0351-9
AB  - Kelch repeat-containing proteins are involved in diverse cellular processes, but only a small subset of plant kelch proteins has been functionally characterized. Thiocyanate-forming protein (TFP) from field-penny cress, Thlaspi arvense (Brassicaceae), is a representative of specifier proteins, a group of kelch proteins involved in plant specialized metabolism. As components of the glucosinolate-myrosinase system of the Brassicaceae, specifier proteins determine the profile of bioactive products formed when plant tissue is disrupted and glucosinolates are hydrolyzed by myrosinases. Here, we describe the crystal structure of TaTFP at a resolution of 1.4 Å. TaTFP crystallized as homodimer. Each monomer forms a six-blade β-propeller with a wide “top” and a narrower “bottom” opening with distinct strand-connecting loops protruding far beyond the lower propeller surface. Molecular modeling and mutational analysis identified residues for glucosinolate aglucone and Fe2+ cofactor binding within these loops. As the first experimentally determined structure of a plant kelch protein, the crystal structure of TaTFP not only enables more detailed mechanistic studies on glucosinolate breakdown product formation, but also provides a new basis for research on the diverse roles and mechanisms of other kelch proteins in plants.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1101
TI  - Chemical constituents of Psorospermum densipunctatum (Hypericaceae)
JO  - Biochem. Syst. Ecol.
PY  - 2015
SP  - 174-176
AU  - Fobofou Tanemossu, S. A.
AU  - Franke, K.
AU  - Schmidt, J.
AU  - Wessjohann, L.
AU  - 
VL  - 59
UR  - 
DO  - 10.1016/j.bse.2015.01.018
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1099
TI  - Unraveling the active hypoglycemic agent trigonelline in Balanites aegyptiaca date fruit using metabolite fingerprinting by NMR
JO  - J. Pharm. Biomed. Anal.
PY  - 2015
SP  - 383-387
AU  - Farag, M. A.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 115
UR  - 
DO  - 10.1016/j.jpba.2015.08.003
AB  - Trigonelline (3-carboxy-1-methyl pyridinium) was identified as a relevant bioactivity and taste imparting component in Balanites aegyptiaca fruit, using 1H NMR of crude extracts without any fractionation or isolation step. The structural integrity of trigonelline was established within the extract matrix via1H NMR, 1H–1H COSY, HMQC and HMBC and by comparison with authentic standard. A quantitative 1H NMR method (qHNMR) was used to determine trigonelline concentrations in the peel and pulp of B. aegyptiaca fruit of 8 and 13 mg g−1, respectively. Trigonelline so far has not been reported from B. aegyptiaca or its genus as it easily escapes LC–MS based detection. Its discovery provides novel insight into the balanite fruits antidiabetic properties as the compound is known for a pronounced hypoglycemic effect. In addition, it is likely to impart the perceptible bitter taste portion to balanites sweet bitter taste. UPLC–MS of the crude extract additionally revealed the fruit flavonoid pattern showing quercetin/isorhamnetin flavonol conjugates in addition to epicatechin, the latter being present at much lower levels.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1098
TI  - Unequivocal glycyrrhizin isomer determination and comparative in vitro bioactivities of root extracts in four Glycyrrhiza species
JO  - J. Adv. Res.
PY  - 2015
SP  - 99-104
AU  - Farag, M. A.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 6
UR  - 
DO  - 10.1016/j.jare.2014.05.001
AB  - Glycyrrhiza glabra, commonly known as licorice, is a popular herbal supplement used for the treatment of chronic inflammatory conditions and as sweetener in the food industry. This species contains a myriad of phytochemicals including the major saponin glycoside glycyrrhizin (G) of Glycyrrhetinic acid (GA) aglycone. In this study, 2D-ROESY NMR technique was successfully applied for distinguishing 18α and 18β glycyrrhetinic acid (GA). ROESY spectra acquired from G. glabra, Glycyrrhiza uralensis and Glycyrrhiza inflata crude extracts revealed the presence of G in its β-form. Anti-inflammatory activity of four Glycyrrhiza species, G, glabra, G. uralensis, G. inflata, and G. echinata roots was assessed against COX-1 inhibition revealing that phenolics rather than glycyrrhizin are biologically active in this assay. G. inflata exhibits a strong cytotoxic effect against PC3 and HT29 cells lines, whereas other species are inactive. This study presents an effective NMR method for G isomer assignment in licorice extracts that does not require any preliminary chromatography or any other purification step.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1097
TI  - Structure-Activity Relationships of Antimicrobial Gallic Acid Derivatives from Pomegranate and Acacia Fruit Extracts against Potato Bacterial Wilt Pathogen
JO  - Chem. Biodivers.
PY  - 2015
SP  - 955-962
AU  - Farag, M. A.
AU  - Al-Mahdy, D. A.
AU  - Salah El Dine, R.
AU  - Fahmy, S.
AU  - Yassin, A.
AU  - Porzel, A.
AU  - Brandt, W.
AU  - 
VL  - 12
UR  - 
DO  - 10.1002/cbdv.201400194
AB  - Bacterial wilts of potato, tomato, pepper, and or eggplant caused by Ralstonia solanacearum are among the most serious plant diseases worldwide. In this study, the issue of developing bactericidal agents from natural sources against R. solanacearum derived from plant extracts was addressed. Extracts prepared from 25 plant species with antiseptic relevance in Egyptian folk medicine were screened for their antimicrobial properties against the potato pathogen R. solancearum by using the disc‐zone inhibition assay and microtitre plate dilution method. Plants exhibiting notable antimicrobial activities against the tested pathogen include extracts from Acacia arabica and Punica granatum. Bioactivity‐guided fractionation of A. arabica and P. granatum resulted in the isolation of bioactive compounds 3,5‐dihydroxy‐4‐methoxybenzoic acid and gallic acid, in addition to epicatechin. All isolates displayed significant antimicrobial activities against R. solanacearum (MIC values 0.5–9 mg/ml), with 3,5‐dihydroxy‐4‐methoxybenzoic acid being the most effective one with a MIC value of 0.47 mg/ml. We further performed a structure–activity relationship (SAR) study for the inhibition of R. solanacearum growth by ten natural, structurally related benzoic acids.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1096
TI  - Phytochemical, antioxidant and antidiabetic evaluation of eight Bauhinia L. species from Egypt using UHPLC–PDA–qTOF-MS and chemometrics
JO  - Phytochemistry
PY  - 2015
SP  - 41-50
AU  - Farag, M. A.
AU  - Sakna, S. T.
AU  - El-fiky, N. M.
AU  - Shabana, M. M.
AU  - Wessjohann, L. A.
AU  - 
VL  - 119
UR  - 
DO  - 10.1016/j.phytochem.2015.09.004
AB  - Bauhinia L. (Fabaceae) comprises ca. 300–350 plant species, many of which are traditionally used in folk medicine for their antidiabetic, antioxidant and anti-inflammatory effects. Bauhinia s.l. recently has been subdivided into 9 genera based on phylogenetic data: Bauhinia s.str., Barklya, Brenierea, Gigasiphon, Lysiphyllum, Phanera, Piliostigma, Schnella (American Phanera) and Tylosema. The aerial parts of 8 species corresponding to 5 genera were analyzed: Bauhinia forficata, Bauhinia variegata, B. variegata var. candida, Bauhinia galpinii, Schnella glabra, Piliostigma racemosa, Phanera vahlii and Lysiphyllum hookeri. Leaves and shoots were subjected to metabolite profiling via UHPLC–PDA–qTOF-MS coupled to multivariate data analyzes to identify compound compositional differences. A total of 90 metabolites were identified including polyphenols and fatty acids; flavonoid conjugates accounted for most of the metabolite variation observed. This study provides a comprehensive map of polyphenol composition in Bauhinia and phytochemical species aggregations are consistent with recent Bauhinia genus taxonomic relationship derived from phylogenetic studies. DPPH radical scavenging and α-glucosidase inhibitory assays were also performed to assess selected aspects of the antioxidant and antidiabetic potential for the examined species with respect to metabolite profiles.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1095
TI  - Integrated comparative metabolite profiling via MS and NMR techniques for Senna drug quality control analysis
JO  - Anal. Bioanal. Chem.
PY  - 2015
SP  - 1937-1949
AU  - Farag, M. A.
AU  - Porzel, A.
AU  - Mahrous, E. A.
AU  - El-Massry, M. M.
AU  - Wessjohann, L. A.
AU  - 
VL  - 407
UR  - 
DO  - 10.1007/s00216-014-8432-1
AB  - Senna alexandrina Mill (Cassia acutifolia and Cassia angustifolia) are used for the laxative medicine Senna. Leaves and pods from two geographically different sources were distinguished from each other via proton nuclear magnetic resonance (1H-NMR) and ultra performance liquid chromatography-mass spectrometry (UPLC-MS) analysis. Under optimized conditions, we were able to simultaneously quantify and identify 107 metabolites including 21 anthraquinones, 24 bianthrones (including sennosides), 5 acetophenones, 25 C/O-flavonoid conjugates, 5 xanthones, 3 naphthalenes, 2 further phenolics, and 9 fatty acids. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) were used to define both similarities and differences among samples. For sample classification based on tissue type (leaf and pod), both UPLC-MS and NMR were found to be more effective in separation than on geographical origin. Results reveal that the amounts of the major classes of bioactives in Senna, i.e., flavonoids and sennosides, varied significantly among organs. Leaves contained more flavonoids and ω-3 fatty acids but fewer benzophenone derivatives than pods. In contrast, pods were more enriched in bianthrones (sennosides). PCA analysis was found to be equally effective in predicting the origin of the commercial Senna preparation using NMR and/or UPLC-MS datasets. Furthermore, a selection of six so far uninvestigated Senna species were analyzed by UPLC-MS. Results revealed that the Senna alata leaf in terms of secondary metabolite composition is the most closely related species to S. alexandrina Mill, showing the highest levels of the anthraquinone “rhein” and flavonoid conjugates. To the best of our knowledge, this study provides the first approach utilizing both UPLC-MS and NMR to reveal secondary metabolite compositional differences among Senna species.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1094
TI  - Binuclear dichlorido(η6-p-cymene)ruthenium(II) complexes with bis(nicotinate)- and bis(isonicotinate)-polyethylene glycol ester ligands
JO  - Appl. Organomet. Chem.
PY  - 2015
SP  - 20-25
AU  - Eichhorn, T.
AU  - Hey-Hawkins, E.
AU  - Maksimović-Ivanić, D.
AU  - Mojić, M.
AU  - Schmidt, J.
AU  - Mijatović, S.
AU  - Schmidt, H.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 29
UR  - 
DO  - 10.1002/aoc.3238
AB  - Neutral binuclear ruthenium complexes 1, 2, 3, 4, 5, 6, 7, 8 of the general formula [{RuCl2(η6‐p‐cym)}2 μ‐(N∩N)] (N∩N = bis(nicotinate)‐ and bis(isonicotinate)‐polyethylene glycol esters: (3‐py)COO(CH2CH2O)nCO(3‐py) and (4‐py)COO(CH2CH2O)nCO(4‐py), n =1–4), as well as mononuclear [RuCl2(η6‐p‐cym)((3‐py)COO(CH2CH2OCH3)‐κN)], complex 9, were synthesized and characterized using elemental analysis and electrospray ionization high‐resolution mass spectrometry, infrared, 1H NMR and 13C NMR spectroscopies. Stability of the binuclear complexes in the presence of dimethylsulfoxide was studied. Furthermore, formation of a cationic complex containing bridging pyridine‐based bidentate ligand was monitored using 1H NMR spectroscopy. Ligand precursors, polyethylene glycol esters of nicotinic (L1 · 2HCl–L4 · 2HCl and L9 · HCl) and isonicotinic acid dihydrochlorides (L5 · 2HCl–L8 · 2HCl), binuclear ruthenium(II) complexes 1, 2, 3, 4, 5, 6, 7, 8 and mononuclear complex 9 were tested for in vitro cytotoxicity against 518A2 (melanoma), 8505C (anaplastic thyroid cancer), A253 (head and neck tumour), MCF‐7 (breast tumour) and SW480 (colon carcinoma) cell lines.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1093
TI  - Trade-offs between physical and chemical carbon-based leaf defence: of intraspecific variation and trait evolution
JO  - J. Ecol.
PY  - 2015
SP  - 1667-1679
AU  - Eichenberg, D.
AU  - Purschke, O.
AU  - Ristok, C.
AU  - Wessjohann, L.
AU  - Bruelheide, H.
AU  - 
VL  - 103
UR  - 
DO  - 10.1111/1365-2745.12475
AB  - Despite recent advances in studies on trade‐offs between plant defence traits, little is known about whether trade‐offs reflect (i) evolutionary constraints at the species level or (ii) allocation constraints at the individual level. Here, we asked to which degree physical and chemical carbon‐based leaf defence traits covary within and across species.We assessed leaf toughness, leaf total phenolic and tannin concentrations for 51 subtropical tree species. Species trait means, sample‐specific values and phylogenetically independent contrasts were used in regression analyses. Phylogenetic signals and trait evolution were assessed along the phylogeny.Analyses of species‐level trait means revealed significant negative trait covariations between physical and chemical defence traits in analyses over all species. These covariations were inconsistent at the within‐species level. All three defence aspects showed strong phylogenetic signals, but differed in the degree of conservatism along the phylogeny. Inclusion of intraspecific trait variability significantly decreased the strength of these covariations. Strong negative covariations were detected between physical and chemical defence traits when phylogenetic non‐independence was accounted for.Synthesis. We addressed two sources of variation (allocation and evolution) independently from each other in the context of trait interrelationships. The observed negative covariations hint at the existence of a trade‐off between physical and chemical defence traits. The finding that intraspecific trait variation contributed less to this relationship suggests that the trade‐off is dominated by evolutionary constraints rather than by carbon allocation constraints.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1092
TI  - Highly Stereoselective Synthesis of Natural-Product-Like Hybrids by an Organocatalytic/Multicomponent Reaction Sequence
JO  - Angew. Chem.
PY  - 2015
SP  - 7731-7735
AU  - Echemendía, R.
AU  - de La Torre, A. F.
AU  - Monteiro, J. L.
AU  - Pila, M.
AU  - Corrêa, A. G.
AU  - Westermann, B.
AU  - Rivera, D. G.
AU  - Paixão, M. W.
AU  - 
VL  - 127
UR  - 
DO  - 10.1002/ange.201412074
AB  - In an endeavor to provide an efficient route to natural product hybrids, described herein is an efficient, highly stereoselective, one‐pot process comprising an organocatalytic conjugate addition of 1,3‐dicarbonyls to α,β‐unsaturated aldehydes followed by an intramolecular isocyanide‐based multicomponent reaction. This approach enables the rapid assembly of complex natural product hybrids including up to four different molecular fragments, such as hydroquinolinone, chromene, piperidine, peptide, lipid, and glycoside moieties. The strategy combines the stereocontrol of organocatalysis with the diversity‐generating character of multicomponent reactions, thus leading to structurally unique peptidomimetics integrating heterocyclic, lipidic, and sugar moieties.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1091
TI  - Highly Stereoselective Synthesis of Natural-Product-Like Hybrids by an Organocatalytic/Multicomponent Reaction Sequence
JO  - Angew. Chem. Int. Ed.
PY  - 2015
SP  - 7621-7625
AU  - Echemendía, R.
AU  - de La Torre, A. F.
AU  - Monteiro, J. L.
AU  - Pila, M.
AU  - Corrêa, A. G.
AU  - Westermann, B.
AU  - Rivera, D. G.
AU  - Paixão, M. W.
AU  - 
VL  - 54
UR  - 
DO  - 10.1002/anie.201412074
AB  - In an endeavor to provide an efficient route to natural product hybrids, described herein is an efficient, highly stereoselective, one‐pot process comprising an organocatalytic conjugate addition of 1,3‐dicarbonyls to α,β‐unsaturated aldehydes followed by an intramolecular isocyanide‐based multicomponent reaction. This approach enables the rapid assembly of complex natural product hybrids including up to four different molecular fragments, such as hydroquinolinone, chromene, piperidine, peptide, lipid, and glycoside moieties. The strategy combines the stereocontrol of organocatalysis with the diversity‐generating character of multicomponent reactions, thus leading to structurally unique peptidomimetics integrating heterocyclic, lipidic, and sugar moieties.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1132
TI  - In vitro effects of binuclear (η6-p-cymene)ruthenium(II) complex containing bridging bis(nicotinate)-polyethylene glycol ester ligand on differentiation pathways of murine Th lymphocytes activated by T cell mitogen
JO  - J. Biol. Inorg. Chem.
PY  - 2015
SP  - 575-583
AU  - Momčilović, M.
AU  - Eichhorn, T.
AU  - Blazevski, J.
AU  - Schmidt, H.
AU  - Kaluđerović, G. N.
AU  - Stosic-Grujicic, S.
AU  - 
VL  - 20
UR  - 
DO  - 10.1007/s00775-015-1242-x
AB  - T cell differentiation into distinct T helper (Th) subpopulations is crucial in governing acquired immune responses as well as some inflammatory and autoimmune disorders. This study investigated potential of the novel neutral binuclear ruthenium(II) complexes 1–8 with general formula [{RuCl2(η6-p-cym)}2μ-(N∩N)] (N∩N = bis(nicotinate)- and bis(iso-nicotinate)-polyethylene glycol esters; (3-py)COO(CH2CH2O) n CO(3-py) and (4-py)COO(CH2CH2O) n CO(4-py); n = 1–4), as well as [RuCl2(η6-p-cym)(nic)] (R1, nic = nicotinate) and [RuCl2(η6-p-cym)(inic)] (R2, inic = isonicotinate) as an immunomodulatory agents capable to direct Th cell differentiation. From all investigated complexes, [{RuCl2(η6-p-cym)}2μ-{(3-py)COO(CH2CH2O)4CO(3-py)}] (4) was selected for further study because it did not affect splenocyte viability (in concentration up to 50 μM), but significantly reduced secretion of representative Th1 cytokine, IFN-γ induced by T cell mitogen. Besides IFN-γ, 4 inhibited dose dependently expression and production of representative Th17 cytokine, IL-17, in these cells. Otherwise, the production of anti-inflammatory cytokines IL-4 and IL-10 was upregulated. Also, 4 significantly increased CD4+CD25+FoxP3+ Treg cell frequency in the activated splenocytes. Moreover, ConA-induced expression of Th1 transcription factors, T-bet and STAT1, as well as of Th17-related protein STAT3 was attenuated upon exposure to 4, while the expression of Th2-related transcription factor GATA3 remained stable. In conclusion, ruthenium(II) complex 4 modulates immune system cell functions in vitro by inhibiting T cell differentiation towards pathogenic Th1/Th17 phenotype and inducing a regulatory phenotype characterized by IL-10 and IL-4 production, which may provide novel therapeutic opportunities for immune-inflammatory and/or autoimmune disorders.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 64
TI  - Macrocycles from Multicomponent Reactions
T2  - Multicomponent Reactions in Organic Synthesis
PB  - 
PY  - 2015
SP  - 231-264
AU  - Wessjohann, L. A.
AU  - Neves Filho, R. A. W.
AU  - Puentes, A. R.
AU  - Morejon, M. C.
AU  - 
VL  - 
UR  - 
SN  - 9783527678174
DO  - 10.1002/9783527678174.ch09
AB  - This chapter focuses on approaches where IMCRs were used in the macrocyclization step itself. In contrast to the conventional approach, IMCR‐based protocols not only mediate the ring‐closing step, but also allow for the incorporation of one or more components as diversity elements into the final product, in an atom‐economical way without additional activation required. However, multicomponent reactions (MCRs) are very suited for the straightforward synthesis of macrocycles endowed with a high level of diversity. The first part concentrates on IMCR‐based macrocyclizations involving a single bifunctional building block (e.g., peptides), followed by those including two bifunctional or trifunctional building blocks. Finally, it discusses the sequential IMCR‐based macrocyclization approaches.
A2  - Zhu, J., et al., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 63
TI  - Enzymatic C-Alkylation of Aromatic Compounds
T2  - Biocatalysis in Organic Synthesis 2
PB  - Science of Synthesis
PY  - 2015
SP  - 177-211
AU  - Wessjohann, L. A.
AU  - Schreckenbach, H. F.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 
UR  - 
SN  - 9783131975317
DO  - 10.1055/sos-SD-215-00096
AB  - 
A2  - Faber, K., et al., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1283
TI  - Synthesis and spectroscopic properties of large single-crystals of Pb(II), Hg(II) and Sr(II) methanesulfonato 1D coordination polymers
JO  - Polyhedron
PY  - 2014
SP  - 282-289
AU  - Đorđević, M.
AU  - Jeremić, D.
AU  - Kaluđerović, G. N.
AU  - Gómez-Ruiz, S.
AU  - Anđelković, B.
AU  - Radanović, D.
AU  - Brčeski, I.
AU  - 
VL  - 80
UR  - 
DO  - 10.1016/j.poly.2014.05.056
AB  - Three new 1D coordination polymers, [Pb2(CH3SO3)4(H2O)2]n, [Hg(CH3SO3)2(H2O)2]n and [Sr(CH3SO3)2(H2O)]n, were synthesized as large single crystals. The crystals were analyzed and characterized by the means of X-ray analysis, IR and NMR spectroscopy, elemental analysis and solid state UV–Vis spectroscopy. The formation of 1D polymeric chains in the crystal structures of the title compounds is affected by the various bonding modes of the bridging methanesulfonate groups. The studied compounds showed no decomposition in the air.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1282
TI  - Synthesis, characterization and in vitro antitumor activity of new palladium(II) complexes with (S,S)-R2edda-type esters
JO  - Polyhedron
PY  - 2014
SP  - 106-111
AU  - Zmejkovski, B. B.
AU  - Savić, A.
AU  - Poljarević, J.
AU  - Pantelić, N.
AU  - Aranđelović, S.
AU  - Radulović, S.
AU  - Grgurić-Šipka, S.
AU  - Kaluđerović, G. N.
AU  - Sabo, T. J.
AU  - 
VL  - 80
UR  - 
DO  - 10.1016/j.poly.2014.02.026
AB  - Six palladium(II) complexes with (S,S)-R2edda-type esters ((S,S)-R2edda-type: (S,S)-eddch = (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate, R = Me, Et, n-Pr, 1–3; (S,S)-pddch = (S,S)-propylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate, R = Et, n-Pr, 4, 5; and (S,S)-eddip = (S,S)-ethylenediamne-N,N′-di-2-propanoate, R = i-Am, 6) were synthesized, characterized by IR, NMR spectroscopy, ESI-MS and elemental analysis. DFT calculations indicate that in case of 1–4, the most stable isomers are with (S,S)- and (R,S)-configuration of nitrogen atoms, but for complex 6 (R,R)- and (R,S)-N,N′-configured isomers. Furthermore, complex 5 was obtained as (S,S)-N,N′ configured isomer. Cytotoxicity study was performed against human cervical adenocarcinoma (HeLa), human alveolar basal adenocarcinoma (A549) and non-cancerous human fetal lung fibroblast (MRC-5) cell lines using colorimetric MTT assay. From the investigated palladium(II) complexes 2, 3 and 5 exhibited highest cytotoxic potential against HeLa (IC50: 28.5 ± 3.9, 29.5 ± 1.3 and 34.3 ± 3.2, respectively).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1277
TI  - An efficient method for the preparation of silyl esters of diphosphoric, phosphoric, and phosphorous acid
JO  - Polyhedron
PY  - 2014
SP  - 133-137
AU  - Wessjohann, L. A.
AU  - Dessoy, M. A.
AU  - 
VL  - 70
UR  - 
DO  - 10.1016/j.poly.2013.12.024
AB  - Tetrakis(trialkylsilyl) diphosphate (alkyl = Me, Et, iPr, tBu) can be obtained in quantitative yield by reacting commercial disodium dihydrogen diphosphate with the respective trialkyl chlorosilane in a triphasic system with formamide. The alkylsilane residues of the diphosphate silyl esters can be either partially or completely hydrolyzed without concurrent cleavage of the P–O–P bond of the diphosphate moiety. The method can be expanded to efficiently produce other persilylated or partially silylated phosphates and phosphites.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1203
TI  - Developmental changes in leaf phenolics composition from three artichoke cvs. (Cynara scolymus) as determined via UHPLC–MS and chemometrics
JO  - Phytochemistry
PY  - 2014
SP  - 67-76
AU  - El Senousy, A. S.
AU  - Farag, M. A.
AU  - Al-Mahdy, D. A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 108
UR  - 
DO  - 10.1016/j.phytochem.2014.09.004
AB  - The metabolomic differences in phenolics from leaves derived from 3 artichoke cultivars (Cynara scolymus): American Green Globe, French Hyrious and Egyptian Baladi, collected at different developmental stages, were assessed using UHPLC–MS coupled to chemometrics. Ontogenic changes were considered as leaves were collected at four different time intervals and positions (top and basal) during artichoke development. Unsupervised principal component analysis (PCA) and supervised orthogonal projection to latent structures-discriminant analysis (O2PLS-DA) were used for comparing and classification of samples harvested from different cultivars at different time points and positions. A clear separation among the three investigated cultivars was revealed, with the American Green Globe samples found most enriched in caffeic acid conjugates and flavonoids vs. other cultivars. Furthermore, these metabolites also showed a marked effect on the discrimination between leaf samples from cultivars harvested at different positions, regardless of the plant age. Metabolite absolute quantifications further confirmed that discrimination was mostly influenced by phenolic compounds, namely caffeoylquinic acids and flavonoids. This study demonstrates an effect of artichoke leaf position, regardless of plant age, on its secondary metabolites composition. To the best of our knowledge, this is the first report for compositional differences among artichoke leaves, based on their positions, via a metabolomic approach and suggesting that top positioned artichoke leaves present a better source of caffeoylquinic acids, compared to basal ones.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1195
TI  - Organozinn(IV)-beladenes mesoporöses SiO2 als biokompatible Strategie bei der Krebstherapie
JO  - Angew. Chem.
PY  - 2014
SP  - 6092-6097
AU  - Bulatović, M. Z.
AU  - Maksimović-Ivanić, D.
AU  - Bensing, C.
AU  - Gómez-Ruiz, S.
AU  - Steinborn, D.
AU  - Schmidt, H.
AU  - Mojić, M.
AU  - Korać, A.
AU  - Golić, I.
AU  - Pérez-Quintanilla, D.
AU  - Momčilović, M.
AU  - Mijatović, S.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 126
UR  - 
DO  - 10.1002/ange.201400763
AB  - Das große therapeutische Potenzial eines Organozinn(IV)‐beladenen nanostrukturierten SiO2 (SBA‐15pSn) wird am Beispiel der Rückbildung eines durch B16‐Zellen induzierten Melanoms bei syngenen C57BL/6‐Mäusen demonstriert. Neben Apoptose als grundlegendem Mechanismus der Antitumorwirkung einer Vielzahl von Chemotherapeutika ist der entscheidende Vorteil dieses mesoporösen zinnhaltigen Materials das Auslösen der Zelldifferenzierung – ein Effekt, der weder für metallbasierte Zytostatika noch für mesoporöse Materialien alleine bisher beobachtet wurde. Dieser nichtaggressive Wirkungsmechanismus ist hochwirksam gegen Tumorzellen aber im gewählten Konzentrationsbereich nichttoxisch für normales Gewebe. JNK‐unabhängige Apoptose (JNK: Jun amino‐terminal kinase), begleitet von der Bildung des melanozytenartigen nichtproliferativen Phänotyps der überlebenden Zellen demonstriert das außergewöhnliche Potenzial von SBA‐15pSn zur Unterdrückung von Tumorwachstum ohne eine unerwünschte kompensatorische Proliferation der erkrankten Zellen als Antwort auf den Zelltod in ihrer Nachbarschaft.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1194
TI  - Organotin(IV)-Loaded Mesoporous Silica as a Biocompatible Strategy in Cancer Treatment
JO  - Angew. Chem. Int. Ed.
PY  - 2014
SP  - 5982-5987
AU  - Bulatović, M. Z.
AU  - Maksimović-Ivanić, D.
AU  - Bensing, C.
AU  - Gómez-Ruiz, S.
AU  - Steinborn, D.
AU  - Schmidt, H.
AU  - Mojić, M.
AU  - Korać, A.
AU  - Golić, I.
AU  - Pérez-Quintanilla, D.
AU  - Momčilović, M.
AU  - Mijatović, S.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 53
UR  - 
DO  - 10.1002/anie.201400763
AB  - The strong therapeutic potential of an organotin(IV) compound loaded in nanostructured silica (SBA‐15pSn) is demonstrated: B16 melanoma tumor growth in syngeneic C57BL/6 mice is almost completely abolished. In contrast to apoptosis as the basic mechanism of the anticancer action of numerous chemotherapeutics, the important advantage of this SBA‐15pSn mesoporous material is the induction of cell differentiation, an effect unknown for metal‐based drugs and nanomaterials alone. This non‐aggressive mode of drug action is highly efficient against cancer cells but is in the concentration range used nontoxic for normal tissue. JNK (Jun‐amino‐terminal kinase)‐independent apoptosis accompanied by the development of the melanocyte‐like nonproliferative phenotype of survived cells indicates the extraordinary potential of SBA‐15pSn to suppress tumor growth without undesirable compensatory proliferation of malignant cells in response to neighboring cell death.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1189
TI  - Molecular models and mutational analyses of plant specifier proteins suggest active site residues and reaction mechanism
JO  - Plant Mol. Biol.
PY  - 2014
SP  - 173-188
AU  - Brandt, W.
AU  - Backenköhler, A.
AU  - Schulze, E.
AU  - Plock, A.
AU  - Herberg, T.
AU  - Roese, E.
AU  - Wittstock, U.
AU  - 
VL  - 84
UR  - 
DO  - 10.1007/s11103-013-0126-0
AB  - As components of the glucosinolate-myrosinase system, specifier proteins contribute to the diversity of chemical defenses that have evolved in plants of the Brassicales order as a protection against herbivores and pathogens. Glucosinolates are thioglucosides that are stored separately from their hydrolytic enzymes, myrosinases, in plant tissue. Upon tissue disruption, glucosinolates are hydrolyzed by myrosinases yielding instable aglucones that rearrange to form defensive isothiocyanates. In the presence of specifier proteins, other products, namely simple nitriles, epithionitriles and organic thiocyanates, can be formed instead of isothiocyanates depending on the glucosinolate side chain structure and the type of specifier protein. The biochemical role of specifier proteins is largely unresolved. We have used two thiocyanate-forming proteins and one epithiospecifier protein with different substrate/product specificities to develop molecular models that, in conjunction with mutational analyses, allow us to propose an active site and docking arrangements with glucosinolate aglucones that may explain some of the differences in specifier protein specificities. Furthermore, quantum-mechanical calculations support a reaction mechanism for benzylthiocyanate formation including a catalytic role of the TFP involved. These results may serve as a basis for further theoretical and experimental investigations of the mechanisms of glucosinolate breakdown that will also help to better understand the evolution of specifier proteins from ancestral proteins with functions outside glucosinolate metabolism.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1186
TI  - Multiple readout assay for hormonal (androgenic and antiandrogenic) and cytotoxic activity of plant and fungal extracts based on differential prostate cancer cell line behavior
JO  - J. Ethnopharmacol.
PY  - 2014
SP  - 721-730
AU  - Bobach, C.
AU  - Schurwanz, J.
AU  - Franke, K.
AU  - Denkert, A.
AU  - Sung, T. V.
AU  - Kuster, R.
AU  - Mutiso, P. C.
AU  - Seliger, B.
AU  - Wessjohann, L. A.
AU  - 
VL  - 155
UR  - 
DO  - 10.1016/j.jep.2014.06.008
AB  - Ethnopharmacological relevanceProstate cancer is one of the most diagnosed forms of cancer among men in western regions. Many traditional applications or phytotherapeutic concepts propose to inhibit the proliferation of prostate cancer cells. In order to detect influences of plant or fungal extracts and derived fractions on androgen receptor signaling pathways, a differentiating cell proliferation assay was established, which enables the simultaneous detection of hormonal and cytotoxic effects.Material and methodsThe well characterized prostate cancer cell lines LNCaP and PC-3 were used in a multiple readout assay. In all, 186 fractions of 23 traditionally used organisms were screened regarding their effects on proliferation of the two prostate cancer cell lines. The fractions were prepared by accelerated solvent extraction followed by gradient extrography. Extracts of the potential hormonally active plants Cibotium barometz, Heteropterys chrysophylla, and Sideroxylon obtusifolium (= Bumelia sartorum) were phytochemically investigated.ResultsFractions from Cibotium barometz, Cortinarius rubellus, Cyrtomium falcatum, Heteropterys chrysophylla, Nephrolepis exaltata, Salvia miltiorrhiza, Sideroxylon obtusifolium, Trichilia emetica, and Trimeria grandifolia exhibited hormonal influences on prostate cancer cells. Cytotoxic activity towards human cell lines was detected for the first time for fractions from Aglaia spectabilis (A. gigantea), Nephrolepis exaltata and Cortinarius brunneus.ConclusionsThe differential behavior of the two prostate cancer cell lines allows the discrimination between potential androgenic or antiandrogenic activities and effects on the estrogen or glucocorticoid receptor as well as cytotoxic activities. The combined cell lines assay can help to assess the biological activities of material used in traditional medicine.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1185
TI  - Synthesis, cytotoxic and hydrolytic studies of titanium complexes anchored by a tripodal diamine bis(phenolate) ligand
JO  - Dalton Trans.
PY  - 2014
SP  - 17422-17433
AU  - Barroso, S.
AU  - Coelho, A. M.
AU  - Gómez-Ruiz, S.
AU  - Calhorda, M. J.
AU  - Žižak, ?.
AU  - Kaluđerović, G. N.
AU  - Martins, A. M.
AU  - 
VL  - 43
UR  - 
DO  - 10.1039/C4DT00975D
AB  - The reactivity, cytotoxic studies and hydrolytic behaviour of diamine bis(phenolate) titanium complexes are reported. The reactions of [Ti(tBu2O2NN′)Cl]2(μ-O) (1) with LiOiPr or HOiPr in the presence of NEt3, aiming at the synthesis of the alkoxido derivative of 1 led to no reaction or to the synthesis of the monomeric complex [Ti(tBu2O2NN′)(OiPr)2] (3), respectively. A small amount of the alkoxidotitanium dimer [Ti(tBu2O2NN′)(OiPr)]2(μ-O) (2) crystallized out of a solution of 3 and DFT calculations showed that the transformation of 1 into 3 is a thermodynamically favorable process in the presence of a base (NEt3) (ΔG = −14.7 kcal mol−1). 2 was quantitatively obtained through the direct reaction of the ligand precursor H2(tBu2O2NN′) with titanium tetra(isopropoxido). Further reaction of 2 with an excess of TMSCl was revealed to be the most suitable method for the preparation of [Ti(tBu2O2NN′)Cl2] (4). 1 and 3 disclosed cytotoxic activity towards HeLa, Fem-x, MDA-MB-361 and K562 cells and 1 exhibited moderate binding affinity to FS-DNA. 1H NMR hydrolysis studies attested the fast decomposition of 4 in the presence of D2O. The hydrolysis of 3 is slower and proceeds through the formation of [Ti(tBu2O2NN′)(OH)]2(μ-O) (5) that was crystallographically characterized. Upon D2O addition 1 immediately forms complex new species, stable in solution for long periods (weeks).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1184
TI  - Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids
JO  - Beilstein J. Org. Chem.
PY  - 2014
SP  - 1017-1022
AU  - Barreto, A. d. F. S.
AU  - Vercillo, O. E.
AU  - Wessjohann, L. A.
AU  - Andrade, C. K. Z.
AU  - 
VL  - 10
UR  - 
DO  - 10.3762/bjoc.10.101
AB  - The synthesis of six cyclic depsipeptoids inspired by the natural depsipeptide sansalvamide A is described. An efficient and fast synthetic strategy was developed using a combination of consecutive isocyanide-based multicomponent reactions (Ugi and Passerini reactions). This methodology can be used to access a variety of cyclic oligodepsipeptoids.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1183
TI  - Dual application of Pd nanoparticles supported on mesoporous silica SBA-15 and MSU-2: supported catalysts for C–C coupling reactions and cytotoxic agents against human cancer cell lines
JO  - RSC Adv.
PY  - 2014
SP  - 54775-54787
AU  - Balbín, A.
AU  - Gaballo, F.
AU  - Ceballos-Torres, J.
AU  - Prashar, S.
AU  - Fajardo, M.
AU  - Kaluđerović, G. N.
AU  - Gómez-Ruiz, S.
AU  - 
VL  - 4
UR  - 
DO  - 10.1039/C4RA11759J
AB  - Two different mesoporous silica-based materials (SBA-15 and MSU-2) have been treated under mild conditions with different quantities of [PdCl2(cod)] (cod = 1,5-cyclooctadiene) to promote the formation of supported palladium nanoparticles (materials of the type SBA-15–Pd and MSU-2–Pd). The synthesized materials have been characterized by different techniques observing that the palladium nanoparticles remain impregnated in the silica. The catalytic activity of the hybrid Pd–silica materials has been tested in Suzuki–Miyaura C–C coupling reactions observing moderate conversion rates in the reactions of 3-bromoanisole with 4-carboxyphenylboronic acid and 2-bromopyridine with 4-carboxyphenylboronic acid. In addition, the synthesized materials showed a good degree of recyclability, being catalytically active in five consecutive catalytic tests. Finally, in order to evaluate the cytotoxicity of the synthesized materials, in vitro tests against five different human cancer cell lines have been carried out, observing high cytotoxic activities of the hybrid systems comparable if not somewhat higher to other systems based on metal complexes supported on mesoporous silicas described previously in the literature. To the best of our knowledge the cytotoxic study reported here represents the first evaluation of the anticancer action of supported palladium nanoparticles in human cancer cells.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1179
TI  - Cytotoxic and antiphytofungal activity of the essential oils from two artemisia species
JO  - World J. Pharm. Res.
PY  - 2014
SP  - 1350-1354
AU  - Ali, N. A. A.
AU  - Wurster, M.
AU  - Denkert, A.
AU  - Al-Sokari, S. S.
AU  - Lindequist, U.
AU  - Wessjohann, L.
AU  - 
VL  - 3
UR  - https://wjpr.net/dashboard/abstract_id/1210
AB  - Hydrodistilled essential oils from aerial parts of Artemisia abyssinica Sch.Bip. ex A. Rich, and Artemisia arborescens L. growing in Yemen were screened for their cytotoxic and antiphytofungal properties as well as their chemical compositions. Twenty-seven components were identified in the essential oils and the main components of these species were found to be davanone (42.34%), camphor (22.88%), nerolidol (8.96%), and chamazulene (4.46%), from A. abyssinica oil and artemisia ketone (51.05%), camphor (14.09%), α-bisabolol (12.56%) and α-phellandrene (8.69%) from A. arborescens. At concentration of 50 and 25 μg/mL, A. arborescens oil showed a strong cytotoxic activity with growth inhibition of 95%(±1.6) and 74%(±3.8) (IC50 of 16.91 μg/mL) against HT29 tumor cells (Human colonic adenocarcinoma cells), while A. abyssinica oil exhibited at concentration of 100 and 50 μg/mL growth inhibition of 71.0% (±12.5) and 27.3%(±14.4) (IC50 of 75.42 μg/mL) respectively. Bioautographic assay was used to evaluate the antiphytofungal activity of the oils against Cladosporium cucumerinum.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1178
TI  - Composition of Essential Oil from Tagetes minuta and its Cytotoxic, Antioxidant and Antimicrobial Activities
JO  - Nat. Prod. Commun.
PY  - 2014
SP  - 265-268
AU  - Ali, N. A. A.
AU  - Sharopov, F. S.
AU  - Al-kaf, A. G.
AU  - Hill, G. M.
AU  - Arnold, N.
AU  - Al-Sokari, S. S.
AU  - Setzer, W. N.
AU  - Wessjohann, L.
AU  - 
VL  - 9
UR  - 
DO  - 10.1177/1934578X1400900233
AB  - The essential oil from the leaves of Tagetes minuta L., growing wild in Yemen, was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry. A total of 28 compounds were identified representing 74.2% of total oil composition. Major components of the essential oil were (Z)-ocimenone (15.9%), (E)-ocimenone (34.8%), (Z)-β-ocimene (8.3%), limonene (2.3%), (Z)-tagetone (1.8%), dihydrotagetone (1.4%) and an unidentified dimethylvinylketone derivative (20.6%). The oil showed moderate cytotoxic activity against MCF-7 breast tumor cells, with an IC50 of 54.7 ± 6.2 μg/mL. In the DPPH radical scavenging assay, T. minuta oil showed potent antiradical activity with an IC50 value of 36 μg/mL. Antimicrobial activity was also investigated on several microorganisms, and the essential oil exhibited high activity against methicillin-resistant Staphylococcus aureus (MRSA) with an inhibition zone of 23 mm. It also exhibited remarkable antifungal activity against Candida albicans with an inhibition zone of 26 mm.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1177
TI  - An efficient one-pot strategy for the highly regioselective metal-free synthesis of 1,4-disubstituted-1,2,3-triazoles
JO  - Chem. Commun.
PY  - 2014
SP  - 11926-11929
AU  - Ali, A.
AU  - Corrêa, A. G.
AU  - Alves, D.
AU  - Zukerman-Schpector, J.
AU  - Westermann, B.
AU  - Ferreira, M. A. B.
AU  - Paixão, M. W.
AU  - 
VL  - 50
UR  - 
DO  - 10.1039/C4CC04678A
AB  - A simple and efficient metal-free methodology for the regioselective synthesis of 1,4-disubstituted-1,2,3-triazoles has been developed by applying a novel inverse electron-demand-1,3-dipolar cycloaddition approach. The practical one-pot metal-free strategy can be accomplished with various alkylidene malononitriles and aromatic azides in the presence of base.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1270
TI  - Rare biscoumarin derivatives and flavonoids from Hypericum riparium
JO  - Phytochemistry
PY  - 2014
SP  - 171-177
AU  - Tanemossu, S. A. F.
AU  - Franke, K.
AU  - Arnold, N.
AU  - Schmidt, J.
AU  - Wabo, H. K.
AU  - Tane, P.
AU  - Wessjohann, L. A.
AU  - 
VL  - 105
UR  - 
DO  - 10.1016/j.phytochem.2014.05.008
AB  - Hypericum riparium A. Chev. is a Cameroonian medicinal plant belonging to the family Guttiferae. Chemical investigation of the methanol extract of the stem bark of H. riparium led to the isolation of four natural products, 7,7′-dihydroxy-6,6′-biscoumarin (1), 7,7′-dihydroxy-8,8′-biscoumarin (2), 7-methoxy-6,7′-dicoumarinyl ether (3), 2′-hydroxy-5′-(7″-methoxycoumarin-6″-yl)-4′-methoxyphenylpropanoic acid (4), together with one known 7,7′-dimethoxy-6,6′-biscoumarin (5), two flavones, 2′-methoxyflavone (6) and 3′-methoxy flavone (7), and two steroids, stigmast-4-en-3-one (8) and ergosta-4,6,8,22-tetraen-3-one (9). In addition, tetradecanoic acid (10), n-pentadecanoic acid (11), hexadecanoic acid (12), cis-10-heptadecenoic acid (13), octadecanoic acid (14) campesterol (15), stigmasterol (16), β-sitosterol (17), stigmastanol (18), β-eudesmol (19), 1-hexadecanol (20), and 1-octadecanol (21) were identified by GC–MS analysis. Compound 4 consists of a phenylpropanoic acid derivative fused with a coumarin unit, while compounds 2 and 3 are rare members of C8–C8′ and C7–O–C6 linked biscoumarins. Their structures were elucidated by UV, IR, extensive 1D- and 2D-NMR experiments and electrospray (ESI) high resolution mass spectrometry (MS) including detailed MS/MS studies. This is the first report on the isolation of biscoumarins from the genus Hypericum, although simple coumarin derivatives have been reported from this genus in the literature. The cytotoxic activities of compounds 2–5 were evaluated against the human prostate cancer cell line PC-3 and the colon cancer cell line HT-29. They do not exhibit any significant cytotoxic activity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1267
TI  - Natural products - learning chemistry from plants
JO  - Biotechnol. J.
PY  - 2014
SP  - 326-336
AU  - Staniek, A.
AU  - Bouwmeester, H.
AU  - Fraser, P. D.
AU  - Kayser, O.
AU  - Martens, S.
AU  - Tissier, A.
AU  - van der Krol, S.
AU  - Wessjohann, L.
AU  - Warzecha, H.
AU  - 
VL  - 9
UR  - 
DO  - 10.1002/biot.201300059
AB  - Plant natural products (PNPs) are unique in that they represent a vast array of different structural features, ranging from relatively simple molecules to very complex ones. Given the fact that many plant secondary metabolites exhibit profound biological activity, they are frequently used as fragrances and flavors, medicines, as well as industrial chemicals. As the intricate structures of PNPs often cannot be mimicked by chemical synthesis, the original plant providers constitute the sole source for their industrial, large‐scale production. However, sufficient supply is not guaranteed for all molecules of interest, making the development of alternative production systems a priority. Modern techniques, such as genome mining and thorough biochemical analysis, have helped us gain preliminary understanding of the enzymatic formation of the valuable ingredients in planta. Herein, we review recent advances in the application of biocatalytical processes, facilitating generation of complex PNPs through utilization of plant‐derived specific enzymes and combinatorial biochemistry. We further evaluate the options of employing heterologous organisms harboring PNP biosynthetic pathways for the production of secondary metabolites of interest.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1256
TI  - SFTA3, a novel protein of the lung: three-dimensional structure, characterisation and immune activation
JO  - Eur. Respir. J.
PY  - 2014
SP  - 447-456
AU  - Schicht, M.
AU  - Rausch, F.
AU  - Finotto, S.
AU  - Mathews, M.
AU  - Mattil, A.
AU  - Schubert, M.
AU  - Koch, B.
AU  - Traxdorf, M.
AU  - Bohr, C.
AU  - Worlitzsch, D.
AU  - Brandt, W.
AU  - Garreis, F.
AU  - Sel, S.
AU  - Paulsen, F.
AU  - Bräuer, L.
AU  - 
VL  - 44
UR  - 
DO  - 10.1183/09031936.00179813
AB  - The lung constantly interacts with numerous pathogens. Thus, complex local immune defence mechanisms are essential to recognise and dispose of these intruders. This work describes the detection, characterisation and three-dimensional structure of a novel protein of the lung (surfactant-associated protein 3 (SFTA3/SP-H)) with putative immunological features. Bioinformatics, biochemical and immunological methods were combined to elucidate the structure and function of SFTA3. The tissue-specific detection and characterisation was performed by using electron microscopy as well as fluorescence imaging. Three-dimensional structure generation and analysis led to the development of specific antibodies and, as a consequence, to the localisation of a novel protein in human lung under consideration of cystic fibrosis, asthma and sepsis. In vitro experiments revealed that lipopolysaccharide induces expression of SFTA3 in the human lung alveolar type II cell line A549. By contrast, the inflammatory cytokines interleukin (IL)-1β and IL-23 inhibit expression of SFTA3 in A549. Sequence- and structure-based prediction analysis indicated that the novel protein is likely to belong to the family of lung surfactant proteins. The results suggest that SFTA3 is an immunoregulatory protein of the lung with relevant protective functions during inflammation at the mucosal sites.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1253
TI  - A Multicomponent Conjugation Strategy to Unique N-Steroidal Peptides: First Evidence of the Steroidal Nucleus as a β-Turn Inducer in Acyclic Peptides
JO  - Chem.-Eur. J.
PY  - 2014
SP  - 13150-13161
AU  - Rivera, D. G.
AU  - Vasco, A. V.
AU  - Echemendía, R.
AU  - Concepción, O.
AU  - Pérez, C. S.
AU  - Gavín, J. A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 20
UR  - 
DO  - 10.1002/chem.201403773
AB  - Constraining small peptides into specific secondary structures has been a major challenge in peptide ligand design. So far, the major solution for decreasing the conformational flexibility in small peptides has been cyclization. An alternative is the use of topological templates, which are able to induce and/or stabilize peptide secondary structures by means of covalent attachment to the peptide. Herein a multicomponent strategy and structural analysis of a new type of peptidosteroid architecture having the steroid as N‐substituent of an internal amide bond is reported. The approach comprises the one‐pot conjugation of two peptide chains (or amino acid derivatives) to aminosteroids by means of the Ugi reaction to give a unique family of N‐steroidal peptides. The conjugation efficiency of a variety of peptide sequences and steroidal amines, as well as their consecutive head‐to‐tail cyclization to produce chimeric cyclopeptide–steroid conjugates, that is, macrocyclic lipopeptides, was assessed. Determination of the three‐dimensional structure of an acyclic N‐steroidal peptide in solution proved that the bulky, rigid steroidal template is capable of both increasing significantly the conformational rigidity, even in a peptide sequence as short as five amino acid residues, and inducing a β‐turn secondary structure even in the all‐s‐trans isomer. This report provides the first evidence of the steroid skeleton as β‐turn inducer in linear peptide sequences.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1251
TI  - Substrate flexibility and reaction specificity of tropinone reductase-like short-chain dehydrogenases
JO  - Bioorg. Chem.
PY  - 2014
SP  - 37-49
AU  - Reinhardt, N.
AU  - Fischer, J.
AU  - Coppi, R.
AU  - Blum, E.
AU  - Brandt, W.
AU  - Dräger, B.
AU  - 
VL  - 53
UR  - 
DO  - 10.1016/j.bioorg.2014.01.004
AB  - Annotations of protein or gene sequences from large scale sequencing projects are based on protein size, characteristic binding motifs, and conserved catalytic amino acids, but biochemical functions are often uncertain. In the large family of short-chain dehydrogenases/reductases (SDRs), functional predictions often fail. Putative tropinone reductases, named tropinone reductase-like (TRL), are SDRs annotated in many genomes of organisms that do not contain tropane alkaloids. SDRs in vitro often accept several substrates complicating functional assignments. Cochlearia officinalis, a Brassicaceae, contains tropane alkaloids, in contrast to the closely related Arabidopsis thaliana. TRLs from Arabidopsis and the tropinone reductase isolated from Cochlearia (CoTR) were investigated for their catalytic capacity. In contrast to CoTR, none of the Arabidopsis TRLs reduced tropinone in vitro. NAD(H) and NADP(H) preferences were relaxed in two TRLs, and protein homology models revealed flexibility of amino acid residues in the active site allowing binding of both cofactors. TRLs reduced various carbonyl compounds, among them terpene ketones. The reduction was stereospecific for most of TRLs investigated, and the corresponding terpene alcohol oxidation was stereoselective. Carbonyl compounds that were identified to serve as substrates were applied for modeling pharmacophores of each TRL. A database of commercially available compounds was screened using the pharmacophores. Compounds identified as potential substrates were confirmed by turnover in vitro. Thus pharmacophores may contribute to better predictability of biochemical functions of SDR enzymes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1249
TI  - Protein modeling and molecular dynamics simulation of the two novel surfactant proteins SP-G and SP-H
JO  - J. Mol. Model.
PY  - 2014
SP  - 2513
AU  - Rausch, F.
AU  - Schicht, M.
AU  - Bräuer, L.
AU  - Paulsen, F.
AU  - Brandt, W.
AU  - 
VL  - 20
UR  - 
DO  - 10.1007/s00894-014-2513-0
AB  - Surfactant proteins are well known from the human lung where they are responsible for the stability and flexibility of the pulmonary surfactant system. They are able to influence the surface tension of the gas–liquid interface specifically by directly interacting with single lipids. This work describes the generation of reliable protein structure models to support the experimental characterization of two novel putative surfactant proteins called SP-G and SP-H. The obtained protein models were complemented by predicted posttranslational modifications and placed in a lipid model system mimicking the pulmonary surface. Molecular dynamics simulations of these protein-lipid systems showed the stability of the protein models and the formation of interactions between protein surface and lipid head groups on an atomic scale. Thereby, interaction interface and strength seem to be dependent on orientation and posttranslational modification of the protein. The here presented modeling was fundamental for experimental localization studies and the simulations showed that SP-G and SP-H are theoretically able to interact with lipid systems and thus are members of the surfactant protein family.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1247
TI  - Palladium-Catalyzed Direct Arylation of Selenophene
JO  - J. Org. Chem.
PY  - 2014
SP  - 5987-5992
AU  - Rampon, D. S.
AU  - Wessjohann, L. A.
AU  - Schneider, P. H.
AU  - 
VL  - 79
UR  - 
DO  - 10.1021/jo500094t
AB  - An efficient and convenient method was developed for the regioselective formation of 2-aryl- or 2,5-diarylselenophenes via a palladium-catalyzed direct arylation. This protocol is suitable for a wide range of aryl halides containing different functional groups. The 2-arylated substrates can undergo an additional regioselective direct arylation event furnishing symmetrical or unsymmetrical 2,5-diaryl selenophenes in good yield. Competition experiments and the role of the acid additive are in agreement with a concerted metalation deprotonation (CMD) pathway.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1246
TI  - Metabolite profiling and fingerprinting of Hypericum species: a comparison of MS and NMR metabolomics
JO  - Metabolomics
PY  - 2014
SP  - 574-588
AU  - Porzel, A.
AU  - Farag, M. A.
AU  - Mülbradt, J.
AU  - Wessjohann, L. A.
AU  - 
VL  - 10
UR  - 
DO  - 10.1007/s11306-013-0609-7
AB  - Hypericum perforatum, commonly known as St. John’s wort, is a popular herbal supplement used for the treatment of mild to moderate depression. The major secondary metabolites of St. John’s wort extracts include phenylpropanoids, flavonoids, xanthones, phloroglucinols, and naphthodianthrones. There are over 400 species in the genus Hypericum world-wide, most of which are little or not characterized in terms of phytochemical or pharmacological properties. Metabolomics techniques were used to investigate the natural product diversity within the genus Hypericum (Hypericaceae) and its correlation to bioactivity, exemplified by cytotoxic properties. Utilizing nuclear magnetic resonance (NMR) fingerprinting and mass spectrometry (MS) metabolic profiling techniques, MS and NMR spectra of extracts from H. perforatum, H. polyphyllum, H. tetrapterum, H. androsaemum, H. inodorum, H. undulatum and H. kouytchense were evaluated and submitted to statistical multivariate analyses. Although comparable score plots in principal component analysis were derived from both MS and NMR datasets, loading plots reveal, that different set of metabolites contribute for species segregation in each dataset. Major peaks in 1H NMR and MS spectra contributing to species discrimination were assigned as those of hyperforins, lipids, chlorogenic and shikimic acid. Shikimic acid and its downstream phenylpropanoids were more enriched in H. perforatum, H. androsaemum, H. kouytchense and H. inodorum extracts; whereas a novel hyperforin was found exclusively in H. polyphyllum. Next to H. perforatum, H. polyphyllum and H. tetrapterum show the highest levels of hypericins, and H. perforatum and H. polyphyllum are highest in phloroglucinols, suggesting that the latter species might be used as an alternative to St. John’s wort. However, the major hyperforin-type compound in H. polyphyllum possesses a novel constitution of yet unknown bioactivity. Anti-cancer in vitro assays to evaluate the ability of extracts from Hypericum species in inhibiting prostate and colon cancer growth suggest that such bioactivity might be predicted by gross metabolic profiling.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1243
TI  - Synthesis and high in vitro cytotoxicity of some (S,S)-ethylenediamine-N,N’-di-2-propanoate dihydrochloride esters
JO  - J. Serb. Chem. Soc.
PY  - 2014
SP  - 649-658
AU  - Pantelić, N.
AU  - Zmejkovski, B. B.
AU  - Stanojković, T. P.
AU  - Jeftić, V. V.
AU  - Radić, G. P.
AU  - Trifunović, S. R.
AU  - Kaluđerović, G. N.
AU  - Sabo, T. J.
AU  - 
VL  - 79
UR  - 
DO  - 10.2298/JSC130512022P
AB  - A novel (S,S)-R2eddip ester, O,O′-diisopentyl-(S,S)-ethylenediamine-N,N′-di-2-propanoate dihydrochloride (1) was synthesized and characterized by IR, 1H- and 13C-NMR spectroscopy, mass spectroscopy and elemental analysis. In vitro antitumor action of 1, and two more R2eddip esters, dialkyl (S,S)-ethylenediamine-N,N′-di-2-propanoate dihydrochlorides, obtained before (alkyl = n-Bu or n-Pe, 2 and 3, respectively), was determined against cervix adenocarcinoma (HeLa), human melanoma (Fem-x), human chronic myelogenous leukemia (K562) cells, and a non-cancerous cell line human embryonic lung fibroblast (MRC-5), using the microculture tetrazolium test MTT assay. Esters 1–3 showed higher cytotoxicity and better selectivity in comparison to cisplatin, used as reference compound. The highest activity was expressed by 1, with IC50(Fem-x) value of 1.51±0.09 μM.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1242
TI  - Cerebral ABC Transporter-common Mechanisms May Modulate Neurodegenerative Diseases and Depression in Elderly Subjects
JO  - Arch. Med. Res.
PY  - 2014
SP  - 738-743
AU  - Pahnke, J.
AU  - Fröhlich, C.
AU  - Paarmann, K.
AU  - Krohn, M.
AU  - Bogdanovic, N.
AU  - Årsland, D.
AU  - Winblad, B.
AU  - 
VL  - 45
UR  - 
DO  - 10.1016/j.arcmed.2014.10.010
AB  - In elderly subjects, depression and dementia often coincide but the actual reason is currently unknown. Does a causal link exist or is it just a reactive effect of the knowledge to suffer from dementia? The ABC transporter superfamily may represent a causal link between these mental disorders. Since the transporters ABCB1 and ABCC1 have been discovered as major β-amyloid-exporting molecules at the blood–brain barrier and ABCC1 was found to be directly activated by St. John&#39;s wort (SJW), depression and dementia certainly share an important pathophysiologic link. It was recognized that herbal anti-depressant formulations made from SJW are at least as effective for the treatment of unipolar depression in old age as classical pharmacotherapy, while having fewer side effects (Cochrane reports, 2008). SJW is known to activate various metabolizing and transport systems in the body, with cytochrome P450 enzymes and ABC transporters being most important.Does the treatment of depression in elderly subjects using pharmacological compounds or phytomedical extracts target a mechanism that also accounts for peptide storage in Alzheimer&#39;s disease and perhaps other proteopathies of the brain?In this review we summarize recent data that point to a common mechanism and present the first promising causal treatment results of demented elderly subjects with distinct SJW extracts. Insufficient trans-barrier clearance may indeed present a common problem in all the proteopathies of the brain where toxic peptides are deposited in a location-specific manner. Thus, activation of efflux molecules holds promise for future treatment of this large group of devastating disorders.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1241
TI  - Penarines A–F, (nor-)sesquiterpene carboxylic acids from Hygrophorus penarius (Basidiomycetes)
JO  - Phytochemistry
PY  - 2014
SP  - 229-233
AU  - Otto, A.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Wessjohann, L.
AU  - Arnold, N.
AU  - 
VL  - 108
UR  - 
DO  - 10.1016/j.phytochem.2014.09.005
AB  - Five sesquiterpene carboxylic acids (1–5) and one nor-sesquiterpene carboxylic acid (6) of the very rare ventricosane type, named penarines A–F, were isolated from fruiting bodies of the basidiomycete Hygrophorus penarius (Hygrophoraceae). This is the first report of (nor)-sesquiterpenes isolated from basidiocarps of the family Hygrophoraceae. Their structures were elucidated on the basis of extensive 1D (1H, 13C) and 2D (HSQC, HMBC, COSY, ROESY) NMR spectroscopic analyses as well as high-resolution mass spectrometry studies. Additionally, the only known member of this rare type of sesquiterpenes, ventricos-7(13)-ene (7), could be identified via headspace GC–MS analysis in a fruiting body of H. penarius. Compounds 1–6 were devoid of remarkable antifungal activity against Cladosporium cucumerinum. Additionally, the cytotoxic activities of compounds 1 and 2 were evaluated against the human prostate cancer cell line PC-3 and the colon cancer cell line HT-29 showing no significant cytotoxic activity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1231
TI  - Cytotoxic Constituents from the Vietnamese Fungus Xylaria schweinitzii
JO  - Nat. Prod. Commun.
PY  - 2014
SP  - 659-660
AU  - Linh, D. T. P.
AU  - Hien, B. T. T.
AU  - Que, D. D.
AU  - Lam, D. M.
AU  - Arnold, N.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Quang, D. N.
AU  - 
VL  - 9
UR  - 
DO  - 10.1177/1934578X1400900518
AB  - Two new fungal pigments named schweinitzins A and B (1-2), together with (S)-torosachrysone-8-O-methyl ether (3) and emodin-6,8-di-O-methyl ether (4) have been isolated from the methanolic extract of the fruit bodies of Xylaria schweinitzii (Xylariaceae) collected in Cuc Phuong national park, Ninh Binh province, Vietnam, by silica gel column chromatography and preparative HPLC. Their structures were elucidated by spectroscopic analysis such as IR, UV-Vis, 2D NMR and FT-ICR-MS. In addition, two compounds (1 and 3) showed strong cytotoxicity against all four cancer cell lines, KB (a human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-1 (human lung carcinoma) and HepG2 (hepatocellular carcinoma).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1229
TI  - The ABC Transporter ABCG1 Is Required for Suberin Formation in Potato Tuber Periderm
JO  - Plant Cell
PY  - 2014
SP  - 3403-3415
AU  - Landgraf, R.
AU  - Smolka, U.
AU  - Altmann, S.
AU  - Eschen-Lippold, L.
AU  - Senning, M.
AU  - Sonnewald, S.
AU  - Weigel, B.
AU  - Frolova, N.
AU  - Strehmel, N.
AU  - Hause, G.
AU  - Scheel, D.
AU  - Böttcher, C.
AU  - Rosahl, S.
AU  - 
VL  - 26
UR  - 
DO  - 10.1105/tpc.114.124776
AB  - The lipid biopolymer suberin plays a major role as a barrier both at plant-environment interfaces and in internal tissues, restricting water and nutrient transport. In potato (Solanum tuberosum), tuber integrity is dependent on suberized periderm. Using microarray analyses, we identified ABCG1, encoding an ABC transporter, as a gene responsive to the pathogen-associated molecular pattern Pep-13. Further analyses revealed that ABCG1 is expressed in roots and tuber periderm, as well as in wounded leaves. Transgenic ABCG1-RNAi potato plants with downregulated expression of ABCG1 display major alterations in both root and tuber morphology, whereas the aerial part of the ABCG1-RNAi plants appear normal. The tuber periderm and root exodermis show reduced suberin staining and disorganized cell layers. Metabolite analyses revealed reduction of esterified suberin components and hyperaccumulation of putative suberin precursors in the tuber periderm of RNA interference plants, suggesting that ABCG1 is required for the export of suberin components.
A2  - 
C1  - Biochemistry of Plant Interactions; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1228
TI  - Structure and Biomedical Applications of Amyloid Oligomer Nanoparticles
JO  - ACS Nano
PY  - 2014
SP  - 11042-11052
AU  - Kumar, S. T.
AU  - Meinhardt, J.
AU  - Fuchs, A.-K.
AU  - Aumüller, T.
AU  - Leppert, J.
AU  - Büchele, B.
AU  - Knüpfer, U.
AU  - Ramachandran, R.
AU  - Yadav, J. K.
AU  - Prell, E.
AU  - Morgado, I.
AU  - Ohlenschläger, O.
AU  - Horn, U.
AU  - Simmet, T.
AU  - Görlach, M.
AU  - Fändrich, M.
AU  - 
VL  - 8
UR  - 
DO  - 10.1021/nn503960h
AB  - Amyloid oligomers are nonfibrillar polypeptide aggregates linked to diseases, such as Alzheimer’s and Parkinson’s. Here we show that these aggregates possess a compact, quasi-crystalline architecture that presents significant nanoscale regularity. The amyloid oligomers are dynamic assemblies and are able to release their individual subunits. The small oligomeric size and spheroid shape confer diffusible characteristics, electrophoretic mobility, and the ability to enter hydrated gel matrices or cells. We finally showed that the amyloid oligomers can be labeled with both fluorescence agents and iron oxide nanoparticles and can target macrophage cells. Oligomer amyloids may provide a new biological nanomaterial for improved targeting, drug release, and medical imaging.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1225
TI  - Hydrazone–diacetyl platinum(II) complexes: Substituent effect on intramolecular N–H⋯O hydrogen-bond strength
JO  - J. Organomet. Chem.
PY  - 2014
SP  - 48-57
AU  - Kluge, T.
AU  - Bette, E.
AU  - Bette, M.
AU  - Schmidt, J.
AU  - Steinborn, D.
AU  - 
VL  - 762
UR  - 
DO  - 10.1016/j.jorganchem.2014.03.030
AB  - Bis(benzylamine)diacetylplatinum(II) (3) reacted with 2-pyridyl-functionalized hydrazones and with diacetyl dihydrazone to yield diacetyl platinum(II) complexes [Pt(COMe)2(2-pyCRNNH2)] (R = H, 4a; Me, 4b; Ph, 4c) and [Pt(COMe)2(H2NNCMe–CMeNNH2)] (5). These complexes showed weak intramolecular N–H⋯O hydrogen bonds where the hydrazone and the acetyl ligand act as H donor and H acceptor, respectively. Using hydrazones 2-pyCRNNHR′ substituted with electron-withdrawing groups R′ resulted in complexes [Pt(COMe)2(2-pyCRNNHR′)] (R/R′ = H/C6H4-p-F, 6d; Me/C6H4-p-F, 6e; H/COMe, 7a; Me/COMe, 7b; H/COPh, 7c; Me/COPh, 7d; H/CO(C6H4-p-F), 7e; Me/CO(C6H4-p-F), 7f) with stronger intramolecular N–H⋯O hydrogen bonds. The isolation of the analogous phenylhydrazone complexes (R′ = Ph) failed on this way, but reactions of the 1D coordination polymer [{Pt(COMe)2}n] (2) with phenylhydrazones resulted in the formation of the desired complexes [Pt(COMe)2(2-pyCRNNHR′)] (R/R′ = H/Ph, 6a; Me/Ph, 6b; Ph/Ph, 6c; H/C6F5, 6f). The constitution of all complexes was unambiguously confirmed analytically, spectroscopically and, in part, by single-crystal X-ray diffraction analyses. Structural and NMR parameters gave evidence that the strength of the N–H⋯O hydrogen bond is increased in the order 5 ≈ 4a–c &lt; 6a–e &lt; 6f ≈ 7a–f. This goes parallel with an activation of the acetyl ligand, but in no case the reaction with amines resulted in the formation of iminoacetyl platinum(II) complexes as it was found in analogous oxime–diacetyl complexes [Pt(COMe)2(2-pyCRNOH)] which have stronger (even than in type 6f/7a–f complexes) intramolecular O–H⋯O hydrogen bonds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1222
TI  - Growing and Processing Conditions Lead to Changes in the Carotenoid Profile of Spinach
JO  - J. Agr. Food Chem.
PY  - 2014
SP  - 4960-4967
AU  - Heymann, T.
AU  - Westphal, L.
AU  - Wessjohann, L.
AU  - Glomb, M. A.
AU  - 
VL  - 62
UR  - 
DO  - 10.1021/jf501136g
AB  - This study aimed to evaluate the influence of different light regimens during spinach cultivation on the isomeric composition of β-carotene. Irradiation with a halogen lamp, which has a wavelength spectrum close to that of daylight, was used to mimic field-grown conditions. The additional use of optical filters was established as a model system for greenhouse cultivation. Field-grown model systems led to a preferential increase of 9-cis-β-carotene, whereas 13-cis-β-carotene was just formed at the beginning of irradiation. Additionally 9,13-di-cis-β-carotene decreased significantly in the presence of energy-rich light. Isomerization of β-carotene was strongly suppressed during irradiation in greenhouse-grown model systems and led to significant differences. These results were verified in biological samples. Authentic field-grown spinach (Spinacia oleracea L.) showed among changes of other isomers a significantly higher level of 9-cis-isomers (7.52 ± 0.14%) and a significantly lower level of 9,13-di-cis-isomers (0.25 ± 0.03%) compared to authentic greenhouse-grown spinach (6.49 ± 0.11 and 0.76 ± 0.05%). Almost all analyzed commercial spinach samples (fresh and frozen) were identified as common field-grown cultivation. Further investigations resulted in a clear differentiation of frozen commercial samples from fresh spinach, caused by significantly higher levels of 13-cis- and 15-cis-β-carotene as a result of industrial blanching processes.
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions
ER  - 


TY  - JOUR
ID  - 1221
TI  - Metabolite Profiling and Fingerprinting of Suillus Species (Basidiomycetes) by Electrospray Mass Spectrometry
JO  - Eur. J. Mass Spectrom.
PY  - 2014
SP  - 85-97
AU  - Heinke, R.
AU  - Schöne, P.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - Schmidt, J.
AU  - 
VL  - 20
UR  - 
DO  - 10.1255/ejms.1235
AB  - The genus Suillus is known for the occurrence of a series of prenylated phenols and boviquinones. The extracts of four different Suillus species (S. bovinus, S. granulatus, S. tridentinus and S. variegatus) were investigated by using rapid ultra-performance liquid chromatography/electrospray ionization mass spectrometry (UPLC/ESI-MS) and direct infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR-MS). While direct infusion ESI-FT-ICR mass spectra give a fast overview concerning the elemental compositions of the compounds and, therefore, hints to the main metabolites, UPLC/ESI-tandem mass spectrometry is shown to be a useful tool for their identification. A principal component analysis (PCA) and hierarchical cluster analysis (HCA) based on the UPLC/ESI-MS clearly showed that the metabolite profiles can be used not only for the identification and classification of such fungi but also as a sophisticated and powerful tool for the chemotaxonomy of fungi. Furthermore, a clear discrimination of various types of biological samples (fruiting bodies versus mycelial cultures) is also possible. The orthogonal partial least squares (OPLS) two-class models of both UPLC/ESI-MS and ESI-FT-ICR-MS possess a clear differentiation of two compared Suillus species representing the between class variation and the within class variation. Based on generated S-plots and loading plots, statistically significant metabolites could be identified as potential biomarker for one species.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1214
TI  - Structural studies and cytotoxic activity against human cancer cell lines of mono and dinuclear tin(IV) complexes with the α,α′-dimercapto-o-xylene ligand
JO  - Inorg. Chim. Acta
PY  - 2014
SP  - 117-122
AU  - Gómez-Ruiz, S.
AU  - Žižak, ?.
AU  - Kaluđerović, G. N.
AU  - 
VL  - 423
UR  - 
DO  - 10.1016/j.ica.2014.04.023
AB  - The reaction of α,α′-dimercapto-o-xylene (H2dmox) with SnPh2Cl2 (1:1) and SnPh3Cl (1:2) in the presence of two equivalents of NEt3 led to the formation of the complexes [SnPh2(dmox)] (1) and [SnPh3(μ-dmox)]2 (2), respectively. Both complexes have been characterized by multinuclear NMR and IR spectroscopy, mass spectrometry and elemental analysis. In addition, the molecular structure of complex 2 has been determined by single crystal X-ray diffraction studies. The cytotoxic activity of 1 and 2 was tested against the tumor cell lines human cervix adenocarcinoma HeLa, breast carcinoma MDA-MB-453, colon carcinoma LS174 and human myelogenous leukemia K562. In addition, the toxicity of both complexes to non-stimulated and stimulated peripheral blood mononuclear cells (PBMC) has been tested. The in vitro cytotoxicity tests show very high antiproliferative activity of both complexes, being much higher that of 2. In addition, this compound shows a higher cytotoxic activity towards cancer cell lines than to non-stimulated and stimulated PBMC, indicating a slight selectivity to cancer cell lines.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1210
TI  - Profiling the chemical content of Ficus lyrata extracts via UPLC-PDA-qTOF-MS and chemometrics
JO  - Nat. Prod. Res.
PY  - 2014
SP  - 1549-1556
AU  - Farag, M. A.
AU  - Abdelfattah, M. S.
AU  - Badr, S. E.
AU  - Wessjohann, L. A.
AU  - 
VL  - 28
UR  - 
DO  - 10.1080/14786419.2014.926353
AB  - This study attempts to elucidate the secondary metabolite profiles of Ficus lyrata leaves and fruits grown in Egypt. Non-targeted metabolite profiling via ultra performance liquid chromatography (UPLC)-qTOF-MS was used to identify various chemical classes in F. lyrata fruits and leaves (i.e. flavonoids, phenolic acids and fatty acids) analysed by chemometrics. A total of 72 metabolites were evaluated via a UPLC-qTOF-MS-based metabolomic study. Seventeen flavonoids were characterised and tentatively identified with the main constituents being catechins/procyanidins, O- and C-linked flavonoid glycosides. The major procyanidins were dimers and trimers comprising (epi)catechin and (epi)afzelechin units, whereas the predominant flavones were C-glycosides of luteolin and apigenin. Aside from these major flavonoid classes, a group of benzoic acids, caffeoylquinic acids, fatty acid and sphingolipids were also annotated. This study provides the most complete map for polyphenol distribution in F. lyrata leaves and fruits and the basis for future investigation of its fruits nutritional value or possible nutraceutical uses.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1209
TI  - Metabolomics driven analysis of six Nigella species seeds via UPLC-qTOF-MS and GC–MS coupled to chemometrics
JO  - Food Chem.
PY  - 2014
SP  - 333-342
AU  - Farag, M. A.
AU  - Gad, H. A.
AU  - Heiss, A. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 151
UR  - 
DO  - 10.1016/j.foodchem.2013.11.032
AB  - Nigella sativa, commonly known as black cumin seed, is a popular herbal supplement that contains numerous phytochemicals including terpenoids, saponins, flavonoids, alkaloids. Only a few of the ca. 15 species in the genus Nigella have been characterized in terms of phytochemical or pharmacological properties. Here, large scale metabolic profiling including UPLC-PDA-MS and GC–MS with further multivariate analysis was utilized to classify 6 Nigella species. Under optimized conditions, we were able to annotate 52 metabolites including 8 saponins, 10 flavonoids, 6 phenolics, 10 alkaloids, and 18 fatty acids. Major peaks in UPLC–MS spectra contributing to the discrimination among species were assigned as kaempferol glycosidic conjugates, with kaempferol-3-O-[glucopyranosyl-(1 → 2)-galactopyranosyl-(1 → 2)-glucopyranoside, identified as potential taxonomic marker for N. sativa. Compared with GC–MS, UPLC–MS was found much more efficient in Nigella sample classification based on genetic and geographical origin. Nevertheless, both GC–MS and UPLC–MS support the remote position of Nigella nigellastrum in relation to the other taxa.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1208
TI  - Metabolomic fingerprints of 21 date palm fruit varieties from Egypt using UPLC/PDA/ESI–qTOF-MS and GC–MS analyzed by chemometrics
JO  - Food Res. Int.
PY  - 2014
SP  - 218-226
AU  - Farag, M. A.
AU  - Mohsen, M.
AU  - Heinke, R.
AU  - Wessjohann, L. A.
AU  - 
VL  - 64
UR  - 
DO  - 10.1016/j.foodres.2014.06.021
AB  - Date palm fruits of the species Phoenix dactylifera exhibit a great diversity in sensory attributes including skin color, smell and taste. This study attempts to elucidate the primary and secondary metabolite profiles of 21 date varieties from Egypt. A major difficulty is sugar rich matrix and skin-fibers embedding the secondary metabolites. A total of 49 metabolites extracted from the fruit skin were evaluated in a UPLC/PDA/ESI–qTOF-MS based metabolomics study. The total phenolic contents of the varieties varied from 233 to 1897 mg/100 g (2.3–19 g/kg) dry weight. The predominant flavones were glycosides of luteolin and apigenin, quercetin conjugates were the principal flavonols, whereas caffeoyl shikimic acid was the main hydroxycinnamic acid conjugate. Aside from these major phenolic classes, a group of sphingolipids, fatty and other organic acids was also identified. The total non-fatty organic acid content correlates with reported shelf lives. GC–MS was further utilized to localize primary metabolites in fruits (i.e. sugars and organic acids) with glucose and fructose accounting for up to 95% of TIC among most varieties. Principal component and clustering analyses reveal that flavonols and sugars, both contribute the most to variety classification. This study provides the most complete map for polyphenol &amp; sugar distribution in Egyptian date fruit varieties. By describing the metabolite profiles in a diverse dataset of P. dactylifera, this study provides the basis for future investigations of date fruit nutritional value beyond providing energy and its potential for nutraceutical enhancement or storability.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1207
TI  - Classification of commercial cultivars of Humulus lupulus L. (hop) by chemometric pixel analysis of two dimensional nuclear magnetic resonance spectra
JO  - Metabolomics
PY  - 2014
SP  - 21-32
AU  - Farag, M. A.
AU  - Mahrous, E. A.
AU  - Lübken, T.
AU  - Porzel, A.
AU  - Wessjohann, L.
AU  - 
VL  - 10
UR  - 
DO  - 10.1007/s11306-013-0547-4
AB  - The development of fast and effective spectroscopic methods that can detect most compounds in an untargeted manner is of increasing interest in plant extracts fingerprinting or profiling projects. Metabolite fingerprinting by nuclear magnetic resonance (NMR) is a fast growing field which is increasingly applied for quality control of herbal products, mostly via 1D 1H NMR coupled to multivariate data analysis. Nevertheless, signal overlap is a common problem in 1H NMR profiles that hinders metabolites identification and results in incomplete data interpretation. Herein, we introduce a novel approach in coupling 2D NMR datasets with principal component analysis (PCA) exemplified for hop resin classification. Heteronuclear multiple bond correlation (HMBC) profile maps of hop resins (Humulus lupulus) were generated for a comparative study of 13 hop cultivars. The method described herein combines reproducible metabolite fingerprints with a minimal sample preparation effort and an experimental time of ca. 28 min per sample, comparable to that of a standard HPLC run. Moreover, HMBC spectra provide not only unequivocal assignment of hop major secondary metabolites, but also allow to identify several isomerization and degradation products of hop bitter acids including the sedative principal of hop (2-methylbut-3-en-2-ol). We do believe that combining 2D NMR datasets to chemometrics, i.e. PCA, has great potential for application in other plant metabolome projects of (commercially relevant) nutraceuticals and or herbal drugs.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1239
TI  - Synthesis of 6-Substituted 1-oxoindanoyl Isoleucine Conjugates and Modeling Studies with the COI1-JAZ Co-Receptor Complex of Lima Bean
JO  - J. Chem. Ecol.
PY  - 2014
SP  - 687-699
AU  - Nakamura, Y.
AU  - Paetz, C.
AU  - Brandt, W.
AU  - David, A.
AU  - Rendón-Anaya, M.
AU  - Herrera-Estrella, A.
AU  - Mithöfer, A.
AU  - Boland, W.
AU  - 
VL  - 40
UR  - 
DO  - 10.1007/s10886-014-0469-2
AB  - The conjugates of 6-substituted 1-oxoindanoyl carboxylic acids with L-isoleucine are mimics of the plant hormone (+)-7-iso-JA-L-Ile (3) that controls and regulates secondary metabolism and stress responses. In order to generate ligands that can be used as hormone-like compounds possessing different biological activities, an efficient and short synthesis of 6-bromo-1-oxoindane-4-carboxylic acid opens a general route to 6-Br-1-oxoindanoyl L-isoleucine conjugate (Br-In-L-Ile) (9a) as a key intermediate for several bioactive 6-halogen-In-L-Ile analogs (7a, 8a, 10a). The 6-ethynyl-In-L-Ile analog (11a) might be a valuable tool to localize macromolecular receptor molecules by click-chemistry. The activities of In-Ile derivatives were evaluated by assays inducing the release of volatile organic compounds (VOCs) in lima bean (Phaseolus lunatus). Each compound showed slightly different VOC induction patterns. To correlate such differences with structural features, modeling studies of In-Ile derivatives with COI-JAZa/b/c co-receptors of P. lunatus were performed. The modeling profits from the rigid backbone of the 1-oxoindanonoyl conjugates, which allows only well defined interactions with the receptor complex.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1238
TI  - Self-regulation of phytoalexin production: a non-biosynthetic enzyme controls alkaloid biosynthesis in cultured cells of Eschscholzia californica
JO  - Plant Cell Tiss. Organ Cult.
PY  - 2014
SP  - 661-676
AU  - Müller, H.
AU  - Heinze, M.
AU  - Heinke, R.
AU  - Schmidt, J.
AU  - Roos, W.
AU  - 
VL  - 119
UR  - 
DO  - 10.1007/s11240-014-0565-6
AB  - Benzophenanthridine alkaloids are strong antimicrobials of Papaveraceae and attractive lead compounds for drug development. The cytotoxicity of these compounds requires the producing plant to limit the pathogen-triggered burst of biosynthesis. Cells of Eschscholzia californica excrete early benzophenanthridines to the cell wall, followed by re-uptake and reduction in the cytoplasm by the detoxifying enzyme sanguinarine reductase. We now discovered that this enzyme is a core component of self-control in alkaloid production. RNAi-based silencing of sanguinarine reductase gave rise to mutants that either show a complete stop of elicitor-triggered alkaloid production or a burst of biosynthesis that severalfold surpasses the wild type level. These unexpected phenotypes reflect impacts of substrate or product of sanguinarine reductase: the substrate, sanguinarine, inhibits phospholipase A2 at the plasma membrane, an initial component of the signal path towards expression of biosynthetic enzymes. The product, dihydrosanguinarine, inhibits enzymes of early biosynthesis, prior to reticuline formation. By tuning these steady states, sanguinarine reductase adjusts the capacity of alkaloid biosynthesis: a minimum activity is sufficient to prevent the blockade of the induction pathway by sanguinarine, while the full activity of the same enzyme causes a limitation of the biosynthetic flow via dihydrosanguinarine.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1237
TI  - Rational design of a ligand-based antagonist of jasmonate perception
JO  - Nat. Chem. Biol.
PY  - 2014
SP  - 671-676
AU  - Monte, I.
AU  - Hamberg, M.
AU  - Chini, A.
AU  - Gimenez-Ibanez, S.
AU  - García-Casado, G.
AU  - Porzel, A.
AU  - Pazos, F.
AU  - Boter, M.
AU  - Solano, R.
AU  - 
VL  - 10
UR  - 
DO  - 10.1038/nchembio.1575
AB  - (+)-7-iso-Jasmonoyl-L-isoleucine (JA-Ile) regulates developmental and stress responses in plants. Its perception involves the formation of a ternary complex with the F-box COI1 and a member of the JAZ family of co-repressors and leads to JAZ degradation. Coronatine (COR) is a bacterial phytotoxin that functionally mimics JA-Ile and interacts with the COI1-JAZ co-receptor with higher affinity than JA-Ile. On the basis of the co-receptor structure, we designed ligand derivatives that spatially impede the interaction of the co-receptor proteins and, therefore, should act as competitive antagonists. One derivative, coronatine-O-methyloxime (COR-MO), has strong activity in preventing the COI1-JAZ interaction, JAZ degradation and the effects of JA-Ile or COR on several JA-mediated responses in Arabidopsis thaliana. Moreover, it potentiates plant resistance, preventing the effect of bacterially produced COR during Pseudomonas syringae infections in different plant species. In addition to the utility of COR-MO for plant biology research, our results underscore its biotechnological potential for safer and sustainable agriculture.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1235
TI  - Probing selected structural regions in the secreted phospholipase A2 from Arabidopsis thaliana for their impact on stability and activity
JO  - Biochimie
PY  - 2014
SP  - 60-66
AU  - Mansfeld, J.
AU  - Schöpfel, M.
AU  - Lorenz, J.
AU  - Trutschel, T.
AU  - Heilmann, I.
AU  - Brandt, W.
AU  - Ulbrich-Hofmann, R.
AU  - 
VL  - 101
UR  - 
DO  - 10.1016/j.biochi.2013.12.015
AB  - In contrast to the well characterized secreted phospholipases A2 (sPLA2) from animals, their homologues from plants have been less explored. Their production in purified form is more difficult, and no data on their stability are known. In the present paper, different variants of the sPLA2 isoform α from Arabidopsis thaliana (AtPLA2α) were designed using a new homology model with the aim to probe the impact of regions that are assumed to be important for stability and catalysis. Moreover tryptophan residues were introduced in critical regions to enable stability studies by fluorescence spectroscopy. The variants were expressed in Escherichia coli and the purified enzymes were analyzed to get first insights into the peculiarities of structure stability and structure activity relationships in plant sPLA2s in comparison with the well-characterized homologous enzymes from bee venom and porcine pancreas. Stability data of the AtPLA2 variants obtained by fluorescence or CD measurements of the reversible unfolding by guanidine hydrochloride and urea showed that all enzyme variants are less stable than the enzymes from animal sources although a similar tertiary core structure can be assumed based on molecular modeling. More extended loop structures at the N-terminus in AtPLA2α are suggested to be the main reasons for the much lower thermodynamic stabilities and cooperativities of the transition curves. Modifications in the N-terminal region (insertion, deletion, substitution by a Trp residue) exhibited a strong positive effect on activity whereas amino acid exchanges in other regions of the protein such as the Ca2+-binding loop and the loop connecting the two central helices were deleterious with respect to activity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 77
TI  - Methyltransferases in Biocatalysis
T2  - Cascade Biocatalysis: Integrating Stereoselective and Environmentally Friendly Reactions
PB  - 
PY  - 2014
SP  - 393-426
AU  - Wessjohann, L.
AU  - Dippe, M.
AU  - Tengg, M.
AU  - Gruber-Khadjawi, M.
AU  - 
VL  - 
UR  - 
SN  - 9783527682492
DO  - 10.1002/9783527682492.ch18
AB  - The methyl group is one of the most widespread functionalities and decorates more than 67% of the top‐selling drugs of 2011.Although significant advances in synthetic chemistry have been achieved allowing the direct methylation, the need for environmentally benign alternatives is growing. As methylation is one of the most common chemical modifications in living cells, a variety of enzymes catalyzing the introduction of methyl groups has been evolved by nature. The enzymes are called methyltransferases (MTs) and are cofactor‐dependent. S‐adenosyl‐L‐methionine (SAM) is by far the most predominant natural source of methyl groups. Since MTs are involved in many cellular processes, their acceptor substrates are diverse, ranging from large biopolymers to small molecules.Their broad substrate spectrum would allow the use of MTs as catalysts for a wide range of biocatalytic methylation and as shown recently for also other alkylation reactions. The technological exploitation is under intensive investigation. As long as an effective recycling system for SAM is lacking, predominantly in vivo applications (cascade reactions using synthetic biology approaches) will emerge.
A2  - Riva, S. &amp; Fessner, W. D., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 76
TI  - Further Components Carboxylic Acid and Amine (Ugi Reaction)
T2  - Multicomponent Reactions 1: General Discussion and Reactions Involving a Carbonyl Compound as Electrophilic Component
PB  - Science of Synthesis
PY  - 2014
SP  - 415-502
AU  - Wessjohann, L. A.
AU  - Kaluđerović, G. N.
AU  - Neves Filho, R. A. W.
AU  - Morejon, M. C.
AU  - Lemanski, G.
AU  - Ziegler, T.
AU  - 
VL  - 
UR  - 
SN  - 9783132064614
DO  - 10.1055/sos-SD-210-00242
AB  - 
A2  - Müller, T. J. J., ed.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 72
TI  - Isolation and characterization of sweet-tasting Dammaran-type glycosides from Mycetia balansae
T2  - Current topics in flavor chemistry &amp; biology - Proceedings of the 10th Wartburg Symposium
PB  - 
PY  - 2014
SP  - 283-287
AU  - Obst, K.
AU  - Sung, T. V.
AU  - Anh, N. T.
AU  - Trai, N. V.
AU  - Porzel, A.
AU  - Mundt, S.
AU  - Paetz, S.
AU  - Reichelt, N. V.
AU  - Engel, K.-H.
AU  - Ley, J. P.
AU  - Wessjohann, L.
AU  - 
VL  - 
UR  - 
AB  - 
A2  - Hofmann, T., et al., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 69
TI  - Quantification of Important Flavor Compounds in Beef Stocks and Correlation to Sensory Results by “Reverse Metabolomics”
T2  - Flavour Science
PB  - 
PY  - 2014
SP  - 15-19
AU  - Degenhardt, A.
AU  - Wittlake, R.
AU  - Seilwind, S.
AU  - Liebig, M.
AU  - Runge, C.
AU  - Hilmer, J.-M.
AU  - Krammer, G.
AU  - Gohr, A.
AU  - Wessjohann, L.
AU  - 
VL  - 
UR  - https://books.google.de/books?id=eUITAAAAQBAJ&amp;pg=PA15&amp;lpg=PA15&amp;dq=Quantification+of+Important+Flavor+Compounds+in+Beef+Stocks+and+Correlation+to+Sensory+Results+by+%E2%80%9CReverse+Metabolomics%E2%80%9D&amp;source=bl&amp;ots=tdHZ9VKvyr&amp;sig=ACfU3U3Bnh-j_OpIBOfGlOEUhjp7qbHiOw&amp;hl=de&amp;sa=X&amp;ved=2ahUKEwiDw5HowubiAhUqMuwKHVg_B_YQ6AEwBHoECAgQAQ#v=onepage&amp;q&amp;f=false
SN  - 9780124017245
DO  - 10.1016/B978-0-12-398549-1.00003-9
AB  - The meaningful correlation of sensory data with analytical data is one of the most challenging tasks in flavor research. In beef stocks in particular, due to the presence of low levels of aroma-active compounds and the taste contribution of non-volatile molecules to the typical “juiciness” character, the consumer encounters a complex matrix situation. The goal of our study was to carry out a comprehensive analysis of all relevant flavor molecules and the correlation to human sensory data.A technique recently developed at the IPB and termed “reverse metabolomics” was used to link biological activity (i.e., sensory data) with variations in the metabolic profile (i.e., analytical data). We used this methodology for the first time to correlate sensorial attributes and GC-MS, LC-MS, and NMR data in culinary beef stocks.Reverse metabolomics was applied to study the link between sensory and chemical composition in a series of freshly prepared culinary beef stocks. A set of 10 different beef stocks was prepared. The degree of liking of the samples was recorded on a hedonic 1–9 scale. Analysis of the stocks was performed by LC-MS, GC-MS, and NMR. 1H-NMR data directly obtained from the meat stock were very complex.Analysis of this dataset by reverse metabolomics revealed some basic structural elements of the key taste compounds, such as carnosine or anserine. The reverse metabolomics correlation of quantitative data with partiality revealed the importance of a set of compounds. This relevance of these compounds has been confirmed by additional sensory experiments which showed an increase in perceived juiciness.
A2  - Ferreira, V. &amp; Lopez, R., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 68
TI  - Interaction of novel sweeteners from Mycetia balansae with the human sweet taste receptor
T2  - Current topics in flavor chemistry &amp; biology - Proceedings of the 10th Wartburg Symposium
PB  - 
PY  - 2014
SP  - 253-257
AU  - Bojahr, J.
AU  - Obst, K.
AU  - Brockhoff, A.
AU  - Reichelt, K.
AU  - Brandt, W.
AU  - Pienkny, S.
AU  - Ley, J. P.
AU  - Wessjohann, L.
AU  - Meyerhof, W.
AU  - 
VL  - 
UR  - 
AB  - In times where overweight and diabetes are major health issues, the demand for taste–optimized low-calorie sweeteners and sweetness enhancers is increasing. The consumer’s preference for natural food ingredients has enforced the search for natural sweeteners. A potential source of such a natural non-nutritive sweetener is the Vietnamese plant Mycetia balansae, which is used for sweetening by locals. We have identified the sweet principle of Mycetia balansae using sensory-guided analysis and characterized its action on the human sweet taste receptor with an integrated approach combining homology modelling and cell-based functional receptor expression.
A2  - Hofmann, T., et al., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 65
TI  - Identification of nitrogen-containing flavonoids as a potent bitter masker supported by combined gustophore modeling and docking studies
T2  - Current topics in flavor chemistry &amp; biology - Proceedings of the 10th Wartburg Symposium
PB  - 
PY  - 2014
SP  - 29-34
AU  - Backes, M.
AU  - Vössing, T.
AU  - Aust, S.
AU  - Pienkny, S.
AU  - Brandt, W.
AU  - Wessjohann, L.
AU  - Ley, J. P.
AU  - 
VL  - 
UR  - 
AB  - Combining (i) a pharmacophore model based on bitter masking actives related to homoeriodictyol and (ii) a homology model of the broadly tuned human bitter receptor hTAS2R10, some new scaffolds for bitter masking compounds based on neoisoflavonoids were deduced. The masking activities of the compounds were predicted via docking of their energy minimized conformers into the putative binding site and subsequent careful analysis of receptor distortion and the number of potential hydrogen bridge bonds. Whereas weak binding candidates showed no masking effect against 500 ppm caffeine, the neoisoflavonoids 3 and 4 and the azaneoisoflavonoids 6 and 7 were able to reduce the bitterness of caffeine by 14 to 34%. Moreover, the new maskers could effectively reduce the bitterness of 100 ppm naringine by about 40-50%.
A2  - Hofmann, T., et al., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1330
TI  - Synthesis, structure and characterization of adenine-based aminocarbene complexes of platinum(II)
JO  - J. Organomet. Chem.
PY  - 2013
SP  - 57-62
AU  - Mihály, T.
AU  - Bette, M.
AU  - Mihály, B.
AU  - Schmidt, J.
AU  - Schmidt, H.
AU  - Steinborn, D.
AU  - 
VL  - 739
UR  - 
DO  - 10.1016/j.jorganchem.2013.04.030
AB  - The reaction of the dinuclear platina-β-diketone [Pt2{(COMe)2H}2(μ-Cl)2] (1) with two equivalents of adenine and its methylated derivatives N6-R,9-R′Ade–H resulted in adenine-based aminocarbene platinum(II) complexes [Pt(COMe)Cl{CMe(N6-R,9-R′Ade–H)-κC,κN}] (R/R′ = Me/Me, 2; H/Me, 3; H/H, 4) whose identities were confirmed by NMR and IR spectroscopies as well as by high-resolution mass spectrometric investigations. Single-crystal X-ray diffraction analyses of complexes 2 and 4·THF revealed relatively short Pt–C and N–C bonds in the aminocarbene–platinum units, which is in accord with a substantial double bond character of these bonds. The electronic structure of these complexes will be further confirmed by DFT calculations as also the course of reaction.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1328
TI  - One-pot synthesis of organophosphate monoesters from alcohols
JO  - Tetrahedron Lett.
PY  - 2013
SP  - 1690-1692
AU  - Lira, L. M.
AU  - Vasilev, D.
AU  - Pilli, R. A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 54
UR  - 
DO  - 10.1016/j.tetlet.2013.01.059
AB  - A one-pot procedure for the phosphorylation of alcohols provides the corresponding phosphate monoesters in improved yields. The protocol features the use of tetrabutylammonium hydrogen phosphate and trichloroacetonitrile, followed by purification of the crude product by flash chromatography on silica gel. The final step, cation exchange chromatography, affords the organophosphates as ammonium salts that are usually required for biochemical applications. The mechanism appears to be phosphate rather than alcohol activation by trichloroacetonitrile.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1326
TI  - Kinetic analysis of Arabidopsis glucosyltransferase UGT74B1 illustrates a general mechanism by which enzymes can escape product inhibition
JO  - Biochem. J.
PY  - 2013
SP  - 37-46
AU  - Kopycki, J.
AU  - Wieduwild, E.
AU  - Kohlschmidt, J.
AU  - Brandt, W.
AU  - Stepanova, A.
AU  - Alonso, J.
AU  - Pedras, M. S.
AU  - Abel, S.
AU  - Grubb, C. D.
AU  - 
VL  - 450
UR  - 
DO  - 10.1042/BJ20121403
AB  - Plant genomes encode numerous small molecule glycosyltransferases which modulate the solubility, activity, immunogenicity and/or reactivity of hormones, xenobiotics and natural products. The products of these enzymes can accumulate to very high concentrations, yet somehow avoid inhibiting their own biosynthesis. Glucosyltransferase UGT74B1 (UDP-glycosyltransferase 74B1) catalyses the penultimate step in the core biosynthetic pathway of glucosinolates, a group of natural products with important functions in plant defence against pests and pathogens. We found that mutation of the highly conserved Ser284 to leucine [wei9-1 (weak ethylene insensitive)] caused only very mild morphological and metabolic phenotypes, in dramatic contrast with knockout mutants, indicating that steady state glucosinolate levels are actively regulated even in unchallenged plants. Analysis of the effects of the mutation via a structural modelling approach indicated that the affected serine interacts directly with UDP-glucose, but also predicted alterations in acceptor substrate affinity and the kcat value, sparking an interest in the kinetic behaviour of the wild-type enzyme. Initial velocity and inhibition studies revealed that UGT74B1 is not inhibited by its glycoside product. Together with the effects of the missense mutation, these findings are most consistent with a partial rapid equilibrium ordered mechanism. This model explains the lack of product inhibition observed both in vitro and in vivo, illustrating a general mechanism whereby enzymes can continue to function even at very high product/precursor ratios.
A2  - 
C1  - Bioorganic Chemistry; Molecular Signal Processing
ER  - 


TY  - JOUR
ID  - 1324
TI  - Activation of Acetyl Ligands through Hydrogen Bonds: A New Way to Platinum(II) Complexes Bearing Protonated Iminoacetyl Ligands
JO  - Organometallics
PY  - 2013
SP  - 7090-7106
AU  - Kluge, T.
AU  - Bette, M.
AU  - Rüffer, T.
AU  - Bruhn, C.
AU  - Wagner, C.
AU  - Ströhl, D.
AU  - Schmidt, J.
AU  - Steinborn, D.
AU  - 
VL  - 32
UR  - 
DO  - 10.1021/om400812w
AB  - The dinuclear platina-β-diketone [Pt2{(COMe)2H}2(μ-Cl)2] (1) reacted with 2-pyridyl-functionalized monoximes and with dioximes in the presence of NaOMe to yield oxime–diacetyl platinum(II) complexes [Pt(COMe)2(2-pyCR═NOH)] (R = H, 4a; Me, 4b; Ph, 4c) and [Pt(COMe)2(HON═CR–CR═NOH)] (R/R = Me/Me, 5a; Ph/Ph, 5b; (CH2)4, 5c; NH2/NH2, 5d), respectively. The strong intramolecular O–H···O hydrogen bonds in these complexes give rise to an activation of the acetyl ligands for Schiff-base type reactions, thus forming with primary amines iminoacetyl platinum complexes [Pt(COMe)(CMe═NHR′)(2-pyCR═NO)] (R/R′ = H/Bn, 6a; Me/Bn, 6b; Ph/Bn, 6c; H/CH2CH2Ph, 6d; H/CH2CH═CH2, 6e; Bn = benzyl) and [{Pt(CMe═NHR′)2(ON═CR–CR═NO)}2] (R/R = Me/Me, 7a–d; Ph/Ph, 8a–d; (CH2)4, 9a; R′ = Bn, a; CH2CH2Ph, b; CH2CH═CH2, c; CH2CH2OH, d). The intramolecular N–H···O hydrogen bonds in type 6–9 complexes make clear that protonated iminoacetyl ligands (i.e., aminocarbene ligands) and deprotoanted oxime ligands are present. These complexes could also be obtained in reactions of [Pt(COMe)2(NH2R′)2] (3) with pyridyl-functionalized monoximes and with dioximes where type 4/5 complexes were found to be intermediates. In solution, the bis(iminoacetyl) complexes 7–9 were found to be present as dimers (as also 8a in the solid state) with smaller amounts of monomers. The importance of hydrogen bonds for activation of acetyl ligands was further evidenced by synthesis of complexes [Pt(COMe)2(2-pyCH═NOMe)] (10) and [Pt(COMe)2(HON═CMe–CMe═NOMe)] (11) bearing O-methylated oxime ligands and their reactivty toward amines. The hydrogen-bond activated acetyl and iminoacetyl ligands in type 5, 7, and 8 complexes were found to undergo in CD3OD solutions facile H/D exchange reactions resulting in complexes bearing C(CD3)═O/C(CD3)═NDR′ ligands. The constitution of all complexes was unambiguously confirmed analytically, spectroscopically and in part by single-crystal X-ray diffraction analyses. Structural and NMR parameters as well as DFT calculations gave evidence for relatively strong intramolecular hydrogen bonds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1323
TI  - Acetylenic 2-phenylethylamides and new isobutylamides from Acmella oleracea (L.) R. K. Jansen, a Brazilian spice with larvicidal activity on Aedes aegypti
JO  - Phytochem. Lett.
PY  - 2013
SP  - 67-72
AU  - Kato Simas, N.
AU  - da Costa Lima Dellamora, E.
AU  - Schripsema, J.
AU  - Salgueiro Lage, C. L.
AU  - Martins de Oliveira Filho, A.
AU  - Wessjohann, L.
AU  - Porzel, A.
AU  - Machado Kuster, R.
AU  - 
VL  - 6
UR  - 
DO  - 10.1016/j.phytol.2012.10.016
AB  - Ethanol extract obtained from dried leaves of Acmella oleracea afforded after a liquid/liquid partition procedure a larvicidal hexane fraction (LC50 = 145.6 ppm) and a non larvicidal dichloromethane one. From the inactive fraction, three amides were identified, two new structures, named deca-6,9-dihydroxy-(2E,7E)-dienoic acid isobutylamide (1), deca-8,9-dihydroxy-(2E,6Z)-dienoic acid isobutylamide (2) and the known nona-2,3-dihydroxy-6,8-diynoic acid 2-phenylethylamide (3). Bioassay-guided chromatographic fractionation of the hexane partition led to the identification of an amide mixture, nona-(2Z)-en-6,8-diynoic acid 2-phenylethylamide (4) and deca-(2Z)-en-6,8-diynoic acid 2-phenylethlylamide (5). This mixture was active against Aedes aegypti larvae at LC50 = 7.6 ppm. Low toxicity of crude extracts and derived fractions on Artemia salina nauplies showed the possibility of using them to control the A. aegypti mosquito larvae. This is the first report on larvicidal activity of acetylenic 2-phenylethylamides and their identification in A. oleracea leaves.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1321
TI  - Evolution of the key alkaloid enzyme putrescine N-methyltransferase from spermidine synthase
JO  - Front. Plant Sci.
PY  - 2013
SP  - 260
AU  - Junker, A.
AU  - Fischer, J.
AU  - Sichhart, Y.
AU  - Brandt, W.
AU  - Dräger, B.
AU  - 
VL  - 4
UR  - 
DO  - 10.3389/fpls.2013.00260
AB  - Putrescine N-methyltransferases (PMTs) are the first specific enzymes of the biosynthesis of nicotine and tropane alkaloids. PMTs transfer a methyl group onto the diamine putrescine from S-adenosyl-l-methionine (SAM) as coenzyme. PMT proteins have presumably evolved from spermidine synthases (SPDSs), which are ubiquitous enzymes of polyamine metabolism. SPDSs use decarboxylated SAM as coenzyme to transfer an aminopropyl group onto putrescine. In an attempt to identify possible and necessary steps in the evolution of PMT from SPDS, homology based modeling of Datura stramonium SPDS1 and PMT was employed to gain deeper insight in the preferred binding positions and conformations of the substrate and the alternative coenzymes. Based on predictions of amino acids responsible for the change of enzyme specificities, sites of mutagenesis were derived. PMT activity was generated in D. stramonium SPDS1 after few amino acid exchanges. Concordantly, Arabidopsis thaliana SPDS1 was mutated and yielded enzymes with both, PMT and SPDS activities. Kinetic parameters were measured for enzymatic characterization. The switch from aminopropyl to methyl transfer depends on conformational changes of the methionine part of the coenzyme in the binding cavity of the enzyme. The rapid generation of PMT activity in SPDS proteins and the wide-spread occurrence of putative products of N-methylputrescine suggest that PMT activity is present frequently in the plant kingdom.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1320
TI  - Inhibition of Human Intestinal α-Glucosidases by Calystegines
JO  - J. Agr. Food Chem.
PY  - 2013
SP  - 5550-5557
AU  - Jocković, N.
AU  - Fischer, W.
AU  - Brandsch, M.
AU  - Brandt, W.
AU  - Dräger, B.
AU  - 
VL  - 61
UR  - 
DO  - 10.1021/jf4010737
AB  - Calystegines are polyhydroxylated nortropane alkaloids found in Convolvulaceae, Solanaceae, and other plant families. These plants produce common fruits and vegetables. The calystegine structures resemble sugars and suggest interaction with enzymes of carbohydrate metabolism. Maltase and sucrase are α-glucosidases contributing to human carbohydrate degradation in the small intestine. Inhibition of these enzymes by orally administered drugs is one option for treatment of diabetes mellitus type 2. In this study, inhibition of maltase and sucrase by calystegines A3 and B2 purified from potatoes was investigated. In silico docking studies confirmed binding of both calystegines to the active sites of the enzymes. Calystegine A3 showed low in vitro enzyme inhibition; calystegine B2 inhibited mainly sucrose activity. Both compounds were not transported by Caco-2 cells indicating low systemic availability. Vegetables rich in calystegine B2 should be further investigated as possible components of a diet preventing a steep increase in blood glucose after a carbohydrate-rich meal.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1316
TI  - Negative ion tandem mass spectrometry of prenylated fungal metabolites and their derivatives
JO  - Anal. Bioanal. Chem.
PY  - 2013
SP  - 177-189
AU  - Heinke, R.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - Schmidt, J.
AU  - 
VL  - 405
UR  - 
DO  - 10.1007/s00216-012-6498-1
AB  - Liquid chromatography negative ion electrospray ionisation tandem mass spectrometry has been used for characterisation of naturally occurring prenylated fungal metabolites and synthetic derivatives. The fragmentation studies allow an elucidation of the decomposition pathways for these compounds. It could be shown, that the prenyl side chain is degraded by successive radical losses of C5 units. Both the benzoquinones and the phenolic derivatives display significant key ions comprising the aromatic ring. In some cases, the formation of significant oxygen-free key ions could be evidenced by high-resolution MS/MS measurements. Furthermore, the different types of basic skeletons, benzoquinones and phenol type as well as cyclic prenylated compounds, can be differentiated by their MS/MS behaviour.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1312
TI  - A quantitative analysis of spontaneous isoaspartate formation from N-terminal asparaginyl and aspartyl residues
JO  - Amino Acids
PY  - 2013
SP  - 1205-1214
AU  - Güttler, B. H.-O.
AU  - Cynis, H.
AU  - Seifert, F.
AU  - Ludwig, H.-H.
AU  - Porzel, A.
AU  - Schilling, S.
AU  - 
VL  - 44
UR  - 
DO  - 10.1007/s00726-012-1454-0
AB  - The formation of isoaspartate (isoAsp) from asparaginyl or aspartyl residues is a spontaneous post-translational modification of peptides and proteins. Due to isopeptide bond formation, the structure and possibly function of peptides and proteins is altered. IsoAsp modifications within the peptide chain have been reported for many cytosolic proteins. Amyloid peptides (Aβ) deposited in Alzheimer’s disease may carry an N-terminal isoAsp-modification. Here, we describe a quantitative investigation of isoAsp-formation from N-terminal Asn and Asp using model peptides similar to the Aβ N-terminus. The study is based on a newly developed separation of peptides using capillary electrophoresis (CE). 1H NMR was employed to validate the basic finding of N-terminal isoAsp-formation from Asp and Asn. Thereby, the isomerization of Asn at neutral pH (0.6 day−1, peptide NGEF) is approximately six times faster than that within the peptide chain (AANGEF). The difference in velocity between Asn and Asp isomerization is approximately 50-fold. In contrast to N-terminal Asn, Asp isomerization is significantly accelerated at acidic pH. The kinetic solvent isotope (kD2O/kH2O) effect of 2.46 suggests a rate-limiting proton transfer in isoAsp-formation. The proton inventory is consistent with transfer of one proton in the transition state, supporting the previous notion of rate-limiting deprotonation of the peptide backbone amide during succinimide-intermediate formation. The study provides evidence for a spontaneous N-terminal isoAsp-formation within peptides and might explain the accumulation of N-terminal isoAsp in amyloid deposits.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1311
TI  - A diterpene synthase from the clary sage Salvia sclarea catalyzes the cyclization of geranylgeranyl diphosphate to (8R)-hydroxy-copalyl diphosphate
JO  - Phytochemistry
PY  - 2013
SP  - 93-99
AU  - Günnewich, N.
AU  - Higashi, Y.
AU  - Feng, X.
AU  - Choi, K.-B.
AU  - Schmidt, J.
AU  - Kutchan, T. M.
AU  - 
VL  - 91
UR  - 
DO  - 10.1016/j.phytochem.2012.07.019
AB  - The bicyclic diterpene (−)-sclareol is accumulated in glandular trichomes in Salvia sclarea (Schmiderer et al., 2008), and is a major terpenoid component of this plant species. It is used as the starting material for Ambrox synthesis, a synthetic ambergris analog used in the flavor and fragrance industry. In order to investigate the formation of sclareol, cDNA prepared from secretory cells of glandular trichomes from S. sclarea inflorescence were randomly sequenced. A putative copalyl diphosphate synthase encoding EST, SscTPS1, was functionally expressed in Escherichia coli. Whereas reaction of geranylgeranyl diphosphate with the putative copalyl diphosphate synthase followed by hydrolysis with alkaline phosphatase yielded a diastereomeric mixture of (13R)- and (13S)-manoyl oxide, HCl hydrolysis yielded (−)-sclareol (1) and 13-epi-sclareol as products. The product of the reaction of SscTPS1 with geranylgeranyl diphosphate was subjected to analysis by LC-negative ion ESI-MS/MS without prior hydrolysis. EPI scans were consistent with copalyl diphosphate to which 18 mass units had added (m/z 467 [M+H]−). The enzymatic reaction was also carried out in the presence of 60% H218O. LC-negative ion ESI-MS/MS analysis established an additional reaction product consistent with the incorporation of 18O. Incubation in the presence of 60% 2H2O resulted in the incorporation of one deuterium atom. These results suggest water capture of the carbocation intermediate, which is known to occur in reactions catalyzed by monoterpene synthases, but has been described only several times for diterpene synthases.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1310
TI  - Anti-Friedel-Crafts-Type Substitution To Form Biaryl Linkages
JO  - Synthesis
PY  - 2013
SP  - 3038-3043
AU  - Gulyas-Fekete, G.
AU  - Boluda, C. J.
AU  - Westermann, B.
AU  - Wessjohann, L. A.
AU  - 
VL  - 45
UR  - 
DO  - 10.1055/s-0033-1339682
AB  - The ipso-substitution of one (or two) hydroxy groups of phloroglucinol with arene nucleophiles (e.g., o-xylene, tetralin, biphenyl) can be achieved easily under Friedel–Crafts-type conditions with or without the use of organic solvents affording a variety of 3,5-dihydroxybiphenyls (57–89% yields). The new method has significant practical advantages compared to classical biaryl-­coupling routes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1305
TI  - Metal ions control product specificity of isoprenyl diphosphate synthases in the insect terpenoid pathway
JO  - Proc. Natl. Acad. Sci. U.S.A.
PY  - 2013
SP  - 4194-4199
AU  - Frick, S.
AU  - Nagel, R.
AU  - Schmidt, A.
AU  - Bodemann, R. R.
AU  - Rahfeld, P.
AU  - Pauls, G.
AU  - Brandt, W.
AU  - Gershenzon, J.
AU  - Boland, W.
AU  - Burse, A.
AU  - 
VL  - 110
UR  - 
DO  - 10.1073/pnas.1221489110
AB  - Isoprenyl diphosphate synthases (IDSs) produce the ubiquitous branched-chain diphosphates of different lengths that are precursors of all major classes of terpenes. Typically, individual short-chain IDSs (scIDSs) make the C10, C15, and C20 isoprenyl diphosphates separately. Here, we report that the product length synthesized by a single scIDS shifts depending on the divalent metal cofactor present. This previously undescribed mechanism of carbon chain-length determination was discovered for a scIDS from juvenile horseradish leaf beetles, Phaedon cochleariae. The recombinant enzyme P. cochleariae isoprenyl diphosphate synthase 1 (PcIDS1) yields 96% C10-geranyl diphosphate (GDP) and only 4% C15-farnesyl diphosphate (FDP) in the presence of Co2+ or Mn2+ as a cofactor, whereas it yields only 18% C10 GDP but 82% C15 FDP in the presence of Mg2+. In reaction with Co2+, PcIDS1 has a Km of 11.6 μM for dimethylallyl diphosphate as a cosubstrate and 24.3 μM for GDP. However, with Mg2+, PcIDS1 has a Km of 1.18 μM for GDP, suggesting that this substrate is favored by the enzyme under such conditions. RNAi targeting PcIDS1 revealed the participation of this enzyme in the de novo synthesis of defensive monoterpenoids in the beetle larvae. As an FDP synthase, PcIDS1 could be associated with the formation of sesquiterpenes, such as juvenile hormones. Detection of Co2+, Mn2+, or Mg2+ in the beetle larvae suggests flux control into C10 vs. C15 isoprenoids could be accomplished by these ions in vivo. The dependence of product chain length of scIDSs on metal cofactor identity introduces an additional regulation for these branch point enzymes of terpene metabolism.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1304
TI  - Phytochemical, phylogenetic, and anti-inflammatory evaluation of 43 Urtica accessions (stinging nettle) based on UPLC–Q-TOF-MS metabolomic profiles
JO  - Phytochemistry
PY  - 2013
SP  - 170-183
AU  - Farag, M. A.
AU  - Weigend, M.
AU  - Luebert, F.
AU  - Brokamp, G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 96
UR  - 
DO  - 10.1016/j.phytochem.2013.09.016
AB  - Several species of the genus Urtica (especially Urtica dioica, Urticaceae), are used medicinally to treat a variety of ailments. To better understand the chemical diversity of the genus and to compare different accessions and different taxa of Urtica, 63 leaf samples representing a broad geographical, taxonomical and morphological diversity were evaluated under controlled conditions. A molecular phylogeny for all taxa investigated was prepared to compare phytochemical similarity with phylogenetic relatedness. Metabolites were analyzed via UPLC–PDA–MS and multivariate data analyses. In total, 43 metabolites were identified, with phenolic compounds and hydroxy fatty acids as the dominant substance groups. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) provides a first structured chemotaxonomy of the genus. The molecular data present a highly resolved phylogeny with well-supported clades and subclades. U. dioica is retrieved as both para- and polyphyletic. European members of the U. dioica group and the North American subspecies share a rather similar metabolite profile and were largely retrieved as one, nearly exclusive cluster by metabolite data. This latter cluster also includes – remotely related – Urtica urens, which is pharmaceutically used in the same way as U. dioica. However, most highly supported phylogenetic clades were not retrieved in the metabolite cluster analyses. Overall, metabolite profiles indicate considerable phytochemical diversity in the genus, which largely falls into a group characterized by high contents of hydroxy fatty acids (e.g., most Andean-American taxa) and another group characterized by high contents of phenolic acids (especially the U. dioica-clade). Anti-inflammatory in vitro COX1 enzyme inhibition assays suggest that bioactivity may be predicted by gross metabolic profiling in Urtica.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1303
TI  - Metabolomics driven analysis of artichoke leaf and its commercial products via UHPLC–q-TOF-MS and chemometrics
JO  - Phytochemistry
PY  - 2013
SP  - 177-187
AU  - Farag, M. A.
AU  - El-Ahmady, S. H.
AU  - Elian, F. S.
AU  - Wessjohann, L. A.
AU  - 
VL  - 95
UR  - 
DO  - 10.1016/j.phytochem.2013.07.003
AB  - The demand to develop efficient and reliable analytical methods for the quality control of herbal medicines and nutraceuticals is on the rise, together with an increase in the legal requirements for safe and consistent levels of active principles. Here, we describe an ultra-high performance liquid chromatography method (UHPLC) coupled with quadrupole high resolution time of flight mass spectrometry (qTOF-MS) analysis for the comprehensive measurement of metabolites from three Cynara scolymus (artichoke) cultivars: American Green Globe, French Hyrious, and Egyptian Baladi. Under optimized conditions, 50 metabolites were simultaneously quantified and identified including: eight caffeic acid derivatives, six saponins, 12 flavonoids and 10 fatty acids. Principal component analysis (PCA) was used to define both similarities and differences among the three artichoke leaf cultivars. In addition, batches from seven commercially available artichoke market products were analysed and showed variable quality, particularly in caffeic acid derivatives, flavonoid and fatty acid contents. PCA analysis was able to discriminate between various preparations, including differentiation between various batches from the same supplier. To the best of our knowledge, this study provides the first approach utilizing UHPLC–MS based metabolite fingerprinting to reveal secondary metabolite compositional differences in artichoke leaf extracts.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1302
TI  - Cytotoxic effect of commercial Humulus lupulus L. (hop) preparations – In comparison to its metabolomic fingerprint
JO  - J. Adv. Res.
PY  - 2013
SP  - 417-421
AU  - Farag, M. A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 4
UR  - 
DO  - 10.1016/j.jare.2012.07.006
AB  - Hops (Humulus lupulus L. Cannabaceae) is an economically important crop, that has drawn more attention in recent years due to its potential pharmaceutical applications. Bitter acids (prenylated polyketides) and prenylflavonoids are the primary phytochemical components that account for hops resins medicinal value. We have previously reported on utilizing untargeted NMR and MS metabolomics for analysis of 13 hops cultivars, revealing for differences in α- versus β-bitter acids composition in derived resins. In this study, effect of ratios of bitter α- to β-acids in hop resins to cytotoxicity of hop resins was investigated. In vitro cell culture assays revealed that β-acids were more effective than α-acids in growth inhibition of PC3 and HT29 cancer cell lines. Nevertheless, hop resins enriched in β-acids showed comparable growth inhibition patterns to α-enriched resins and suggesting that bioactivity may not be easily predicted by metabolomics and/or gross metabolic profiling in hops.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1297
TI  - Synthesis, characterization and cytotoxicity studies of platinum(II) complexes with amino acid ligands in various coordination modes
JO  - Inorg. Chim. Acta
PY  - 2013
SP  - 472-480
AU  - Chaudhuri, S. R.
AU  - Kaluđerović, G. N.
AU  - Bette, M.
AU  - Schmidt, J.
AU  - Schmidt, H.
AU  - Paschke, R.
AU  - Steinborn, D.
AU  - 
VL  - 394
UR  - 
DO  - 10.1016/j.ica.2012.08.034
AB  - Reactions of [Pt(CO3)(PPh3)2]·CH2Cl2 (1) with non-substituted and alkyl substituted amino acids, NH(R)CH(R′)CO2H (R/R′ = H/Me, L1; H/iPr, L2; H/CH2CHMe2, L3; Me/H, L4; Et/H, L5), in the presence of Tl[PF6] in methanol afforded with liberation of CO2 the formation of platinum(II) complexes of the type [Pt(PPh3)2{NHR–CHR′–C(O)O-κN,κO}][PF6] (R/R′ = H/Me, 2; H/iPr, 3; H/CH2CHMe2, 4; Me/H, 5; Et/H, 6). Single-crystal X-ray diffraction analysis of complex 4 exhibited a square-planar coordination of the platinum atom having coordinated two triphenylphosphane ligands and a deprotonated κN,κO-coordinated leucine ligand (L3−H). On varying the pKa value of the amino group, platinum(II) complexes with different coordination modes of amino acid ligands were obtained. Thus, treatment of complex 1 with N-acetyl l-alanine (L6), possessing a comparatively highly acidic NH proton, in 1:1 ratio in methanol resulted in the formation of [Pt(PPh3)2{N(COMe)–CHMe–C(O)O-κN,κO}] (7), while reacting N-phenyl glycine (L7) having a moderately acidic NH proton with complex 1 afforded a mixture of complexes [Pt(PPh3)2{NPh–CH2–C(O)O-κN,κO}] (8) and [Pt(PPh3)2{NHPh–CH2–C(O)O-κO}2] (10). Treatment of complex 1 with two equivalents of L6/L7 in dichloromethane resulted in the formation of [Pt(PPh3)2{NHR–CHR′–C(O)O-κO}2] (R/R′ = COMe/Me, 9; Ph/H, 10). An analogous reactivity was observed for l-lactic acid on treating with complex 1 in 1:1 and 2:1 ratio resulting in [Pt(PPh3)2{O–CHMe–C(O)O-κO,κO′}] (11) and [Pt(PPh3)2{HO–CHMe–C(O)O-κO}2] (12). The identities of all complexes have been proven by NMR (1H, 13C, 31P) spectroscopic and high-resolution ESI mass-spectrometric investigations. In vitro cytotoxicity studies against human tumor cell lines (8505C, A2780, HeLa, SW480, and MCF-7) showed the highest activities for the neutral complex 7. Furthermore, complexes 7 and 9 against the A2780 cell line induced an apoptotic mode of cell death, which was further supported by morphological investigation and DNA laddering. Cell cycle perturbation studies showed that both complexes induced faster cell death than cisplatin.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1293
TI  - Higher-order multicomponent reactions: beyond four reactants
JO  - Chem. Soc. Rev.
PY  - 2013
SP  - 4948-4962
AU  - Brauch, S.
AU  - van Berkel, S. S.
AU  - Westermann, B.
AU  - 
VL  - 42
UR  - 
DO  - 10.1039/C3CS35505E
AB  - Multicomponent reactions (MCRs) are by far the most successful class of reactions leading to high structural diversity and molecular complexity through a single transformation. As part of the ongoing search for pharmacologically active lead structures, the obtained structural diversity allows for the fast exploration of a large chemical space. Not surprisingly, the development of MCRs, leading to new structural frameworks or serving as key transformations in the total synthesis of natural products, has expanded rapidly over the last few decades. To date a multitude of new three- and four-component reactions have already been described; however, examples of “higher-order” MCRs where five or even more components are combined in a single reaction vessel are remarkably scarce. This tutorial review aims to critically describe the developments achieved in recent years, charting the ideas, challenges, and milestone reactions that were essential for the progress of this field.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1291
TI  - Diacetylplatinum(II) Complexes with κ2-Coordinated Tris(pyridyl)methanol and Tris(pyridyl)methyl Ether Ligands: Structural Insight into the Ligand Dynamics in Solution
JO  - Organometallics
PY  - 2013
SP  - 2216-2227
AU  - Bette, M.
AU  - Kluge, T.
AU  - Schmidt, J.
AU  - Steinborn, D.
AU  - 
VL  - 32
UR  - 
DO  - 10.1021/om400091h
AB  - Reactions of the bis(benzylamine)platinum(II) complex [Pt(COMe)2(NH2Bn)2] (2; Bn = benzyl) with (2-py)3COR (2-py = 2-pyridyl), (2-py)2PhCOR, and (2-py)2(m-Tol)COR (m-Tol = 3-methylphenyl) afforded the neutral diacetylplatinum(II) complexes [Pt(COMe)2{(2-py)3COR}] (R = H (3a), Me (3b), Et (3c), Bn (3d)), [Pt(COMe)2{(2-py)2PhCOR}] (R = H (4a), Me (4b)), and [Pt(COMe)2{(2-py)2(m-Tol)COR}] (R = H (5a) Me (5b)), respectively, having, due to a κ2 coordination of the ligands, a 2-pyridyl (3), a phenyl (4), or a m-tolyl (5) ring as the pendant group. The identities of all complexes were unambiguously proved by high-resolution mass spectrometric investigations and by NMR (1H, 13C, 195Pt) and IR spectroscopy as well as by single-crystal X-ray diffraction analyses (3a–d). In methanol solution, complexes 3b–d and 5b show a dynamic behavior. The thermodynamic parameters of these dynamics have been determined by variable-temperature 1H NMR measurements (Eyring plots). Furthermore, extensive DFT calculations will be presented, which indicate that the dynamics are caused by the interplay of hindered and respectively unhindered rotations of the substituent R and/or the pendant group.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1290
TI  - Diacetylplatinum(II) and -platinum(IV) Complexes Bearing κ2- and κ3-Coordinated Tris(pyrazolyl)methane Ligands: Investigations on the Synthesis, Fluxionality, and Reactivity in Relation to the Substitution Pattern of the Ligands
JO  - Eur. J. Inorg. Chem.
PY  - 2013
SP  - 2395-2410
AU  - Bette, M.
AU  - Schmidt, J.
AU  - Steinborn, D.
AU  - 
VL  - 2013
UR  - 
DO  - 10.1002/ejic.201201468
AB  - Reactions of the dinuclear platina‐β‐diketone [Pt2{(COMe)2H}2(μ‐Cl)2] (1) with HC(pz)3 and HC(3,5‐Me2pz)3 (pz = pyrazol‐1‐yl; 3,5‐Me2pz = 3,5‐dimethylpyrazol‐1‐yl) afforded cationic, thermally labile diacetyl(hydrido)platinum(IV) complexes [Pt(COMe)2H{(pz)3CH}]Cl (3a) and [Pt(COMe)2H{(3,5‐Me2pz)3CH}]Cl (3b) with κ3‐coordinated tris(pyrazolyl)methane ligands, which were found to react with NaOH or NEt3 to yield neutral diacetylplatinum(II) complexes with κ2‐coordinated tris(pyrazolyl)methane ligands {[Pt(COMe)2{(pz)3CH}] (4a); [Pt(COMe)2{(3,5‐Me2pz)3CH}] (4b)}. In 4a/b, a molecular rearrangement (decoordination of a pyrazolyl ring and coordination of the originally pendant one) has been found that has been investigated by variable‐temperature 1H NMR spectroscopic measurements (coalescence method) as well as by DFT calculations. Diacetylplatinum(II) complexes 4 were found to react in oxidative addition reactions with ROTf (R = H, Me; OTf = trifluoromethanesulfonate) and methyl iodide to yield cationic diacetylplatinum(IV) complexes of the type [Pt(COMe)2R{(pz)3CH}]X (R/X = H/OTf, 5a; Me/OTf, 6a; Me/I, 7a) and [Pt(COMe)2R{(3,5‐Me2pz)3CH}]X [R/X = H/OTf (5b), Me/OTf (6b), Me/I (7b)] with κ3‐bonded tris(pyrazolyl)methane ligands. Treatment of 4b with alkynyliodine(III) reagents of the type [IPh(C≡CR)]X (R/X = SiMe3/OTf, Ph/OTf, tBu/OTos, iPr/OTos; OTos = p‐toluenesulfonate) led to the formation of cationic diacetyl(alkynyl)platinum(IV) complexes [Pt(COMe)2(C≡CR){(3,5‐Me2pz)3CH}]X [R/X = SiMe3/OTf (8a), Ph/OTf (8b), tBu/OTos (8c), iPr/OTos (8d)]. The identities of all platinum complexes were unambiguously proven by high‐resolution mass spectrometric investigations, by NMR (1H, 13C, 195Pt) and IR spectroscopy, as well as by single‐crystal X‐ray diffraction analyses (4a, 4b, 7a, 8a/d). The constitution of the thermally labile complexes 3a/b has been confirmed by low‐temperature (–80 °C) NMR (1H, 13C) spectroscopic measurements. The electronic and steric influence of the additional methyl groups in HC(3,5‐Me2pz)3 on reactivity, stability, and properties of the investigated compounds will be discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1289
TI  - Biotechnologie von Morgen: DECHEMA/VAAM-Fachgruppe „Biotransformationen“
JO  - BIOspektrum
PY  - 2013
SP  - 208-210
AU  - Berger, R.
AU  - Bornscheuer, U.
AU  - Liese, A.
AU  - Schwaneberg, U.
AU  - Syldatk, C.
AU  - Wessjohann, L.
AU  - 
VL  - 19
UR  - 
DO  - 10.1007/s12268-013-0291-3
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1288
TI  - Phytochemical study on the plants of the antidrug medication heantos 4: Part 3. Homoisoflavonoid, flavonoid and phenolic compounds
JO  - Vietnam J. Chem.
PY  - 2013
SP  - 358-362
AU  - Anh, N. T. H.
AU  - Thuy, T. T.
AU  - Sung, T. V.
AU  - Dan, T. K.
AU  - Chinh, N. B.
AU  - Quang, N.
AU  - Franke, K.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 51
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1287
TI  - Phytochemical study on the plants of the antidrug medication heantos 4: Part 2. Terpenoid- and steroid compounds
JO  - Vietnam J. Chem.
PY  - 2013
SP  - 190-194
AU  - Anh, N. T. H.
AU  - Thuy, T. T.
AU  - Sung, T. V.
AU  - Dan, T. K.
AU  - Chinh, N. B.
AU  - Quang, N.
AU  - Franke, K.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 51
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1286
TI  - Antimicrobial, Antioxidant, and Cytotoxic Activities of the Essential Oil of Tarchonanthus camphoratus
JO  - Nat. Prod. Commun.
PY  - 2013
SP  - 683-686
AU  - Ali, N. A. A.
AU  - Al-Fatimi, M. A.
AU  - Crouch, R. A.
AU  - Denkert, A.
AU  - Setzer, W. N.
AU  - Wessjohann, L.
AU  - 
VL  - 8
UR  - 
DO  - 10.1177/1934578X1300800534
AB  - The leaf essential oil of Tarchonanthuscamphoratus(Asteraceae) was obtained by hydrodistillation and analyzed by GC-MS. Fifty-six components were characterized, representing 94.2% of the total oil with oxygenated monoterpenes (48.3%) and oxygenated sesquiterpenes (32.7%) as the major groups. The principal constituents were identified as endo-fenchol (21.2%), trans-pinene hydrate (8.8%), caryophyllene oxide (7.5%), α-terpineol (6.4%), τ-cadinol (6.4%), and α-cadinol (5.2%). The essential oil was evaluated for its antimicrobial activity using a disc diffusion assay resulting in the moderate inhibition of a number of common human pathogenic bacteria, including methicillin-resistant Staphylococcus aureus(MRSA) and the yeast Candida albicans. The inhibition zones varied from 10 to 14mm/disc. Furthermore, the antioxidant capacity of the essential oil was examined using an in vitroradical scavenging activity test. The T. camphoratus essential oil scavenged 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), resulting in an IC50value of 5.6 mg/mL. At concentrations of 100 and 50μg/mL, the oil showed cytotoxic activity, with growth inhibition of 59.1% (±4.2), and 16.2% (±8.7) against HT29 tumor cells (human colonic adenocarcinoma cells), respectively(IC50 = 84.7 ± 7.5 μg/mL).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1367
TI  - Boron-Zinc Exchange in The Diastereoselective Arylation of Sugar-Based Aldehydes­: Stereoselective Synthesis of (+)-7-epi-Goniofufurone and Analogues
JO  - Synthesis
PY  - 2013
SP  - 2222-2233
AU  - Wouters, A. D.
AU  - Bessa, A. B.
AU  - Sachini, M.
AU  - Wessjohann, L. A.
AU  - Lüdtke, D. S.
AU  - 
VL  - 45
UR  - 
DO  - 10.1055/s-0033-1339285
AB  - The substrate-controlled diastereoselective arylation of chiral aldehydes readily available from carbohydrates is described, using the boron–zinc exchange reaction to generate the transferable aryl groups. The methodology developed was applied to the total synthesis of the styryllactone (+)-7-epi-goniofufurone and analogues thereof.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1364
TI  - A single amino acid determines position specificity of an Arabidopsis thaliana CCoAOMT-like O-methyltransferase
JO  - FEBS Lett.
PY  - 2013
SP  - 683-689
AU  - Wils, C. R.
AU  - Brandt, W.
AU  - Manke, K.
AU  - Vogt, T.
AU  - 
VL  - 587
UR  - 
DO  - 10.1016/j.febslet.2013.01.040
AB  - Caffeoyl‐coenzyme A O‐methyltransferase (CCoAOMT)‐like proteins from plants display a conserved position specificity towards the meta‐position of aromatic vicinal dihydroxy groups, consistent with the methylation pattern observed in vivo. A CCoAOMT‐like enzyme identified from Arabidopsis thaliana encoded by the gene At4g26220 shows a strong preference for methylating the para position of flavanones and dihydroflavonols, whereas flavones and flavonols are methylated in the meta‐position. Sequence alignments and homology modelling identified several unique amino acids compared to motifs of other CCoAOMT‐like enzymes. Mutation of a single glycine, G46 towards a tyrosine was sufficient for a reversal of the unusual para‐ back to meta‐O‐methylation of flavanones and dihydroflavonols.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1363
TI  - CuAAC-mediated diversification of aminoglycoside–arginine conjugate mimics by non-reducing di- and trisaccharides
JO  - Carbohyd. Res.
PY  - 2013
SP  - 61-67
AU  - Westermann, B.
AU  - Dörner, S.
AU  - Brauch, S.
AU  - Schaks, A.
AU  - Heinke, R.
AU  - Stark, S.
AU  - van Delft, F. L.
AU  - van Berkel, S. S.
AU  - 
VL  - 371
UR  - 
DO  - 10.1016/j.carres.2013.02.003
AB  - Di- and triguanidinylation of trehalose, sucrose, and melizitose has been achieved via a Huisgen-cycloaddition approach. They can serve as aminoglycoside–arginine conjugate mimics, which has been demonstrated by their biological profiles in assays against Bacillus subtilis. For comparative studies, tetraguanidinylated neamine and kanamycin derivatives have also been synthesized and evaluated
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1362
TI  - Total Synthesis of Epothilone D: The Nerol/Macroaldolization Approach
JO  - J. Org. Chem.
PY  - 2013
SP  - 10588-10595
AU  - Wessjohann, L. A.
AU  - Scheid, G. O.
AU  - Eichelberger, U.
AU  - Umbreen, S.
AU  - 
VL  - 78
UR  - 
DO  - 10.1021/jo401355r
AB  - A highly convergent and stereocontrolled synthesis of epothilone D (4) is reported. Key features are a cheap and Z-selective synthesis of the northern half based on nerol and acetoacetate and chromium(II)-mediated Reformatsky reactions as a powerful tool for chemoselective asymmetric carbon–carbon bond formations, including an unusual stereospecific macroaldolization.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1361
TI  - Solid-phase synthesis of reduced selenocysteine tetrapeptides and their oxidized analogs containing selenenylsulfide eight-membered rings
JO  - Mol. Divers.
PY  - 2013
SP  - 537-545
AU  - Wessjohann, L. A.
AU  - Schneider, A.
AU  - Kaluđerović, G. N.
AU  - Brandt, W.
AU  - 
VL  - 17
UR  - 
DO  - 10.1007/s11030-013-9454-x
AB  - A series of protected and reduced forms of model tetrapeptides that mimic the C-terminus of human thioredoxin reductases were obtained in good yields, using solid-phase peptide synthesis (SPPS). SPPS was performed on the Knorr Amide MBHA resin for Fmoc chemistry using especially protected cystein and selenocystein derivatives. All amino acids have been coupled according to the HBTU/HOBt/DIPEA method. Furthermore, the corresponding oxidized peptides containing eight-membered rings with intramolecular S–S and S–Se bridges were prepared via I2/MeOH or DMSO/TFA oxidation, respectively.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1360
TI  - Alkylating enzymes
JO  - Curr. Opin. Chem. Biol.
PY  - 2013
SP  - 229-235
AU  - Wessjohann, L. A.
AU  - Keim, J.
AU  - Weigel, B.
AU  - Dippe, M.
AU  - 
VL  - 17
UR  - 
DO  - 10.1016/j.cbpa.2013.02.016
AB  - Chemospecific and regiospecific modifications of natural products by methyl, prenyl, or C-glycosyl moieties are a challenging and cumbersome task in organic synthesis. Because of the availability of an increasing number of stable and selective transferases and cofactor regeneration processes, enzyme-assisted strategies turn out to be promising alternatives to classical synthesis. Two categories of alkylating enzymes become increasingly relevant for applications: firstly prenyltransferases and terpene synthases (including terpene cyclases), which are used in the production of terpenoids such as artemisinin, or meroterpenoids like alkylated phenolics and indoles, and secondly methyltransferases, which modify flavonoids and alkaloids to yield products with a specific methylation pattern such as 7-O-methylaromadendrin and scopolamine.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1356
TI  - Phytochemical study on the plants of the antidrug medication heantos 4: Part 4. Phthalides, fatty acids, oligosaccharide esters and miscellaneous compounds
JO  - Vietnam J. Chem.
PY  - 2013
SP  - 546-550
AU  - Thuy, T. T.
AU  - Anh, N. T. H.
AU  - Sung, T. V.
AU  - Dan, T. K.
AU  - Chinh, N. B.
AU  - Quang, N.
AU  - Franke, K.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 51
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1355
TI  - Phytochemical study on the plants of the antidrug medication heantos 4: Part 1. Alkaloids and other nitrogen containing compounds
JO  - Vietnam J. Chem.
PY  - 2013
SP  - 185-189
AU  - Thuy, T. T.
AU  - Anh, N. H.
AU  - Sung, T. V.
AU  - Dan, T. K.
AU  - Chinh, N. B.
AU  - Quang, N.
AU  - Franke, K.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 51
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1353
TI  - Snap-shot of Serine Carboxypeptidase-like Acyltransferase Evolution: The Loss of Conserved Disulphide Bridge is Responsible for the Completion of Neo-functionalization
JO  - J. Phylogenet. Evol. Biol.
PY  - 2013
SP  - 115
AU  - Stehle, F.
AU  - Götsch, F.
AU  - Wray, V.
AU  - Schmidt, J.
AU  - Strack, D.
AU  - Brandt, W.
AU  - 
VL  - 1
UR  - 
DO  - 10.4172/2329-9002.1000115
AB  - In this work, it is shown that the At2g23010 gene product encodes 1-O-sinapoyl-β-glucose:1-O-sinapoyl-β-glucose sinapoyltransferase (SST). In contrast to all other functional characterized acyltransferases, the SST protein is highly specific towards this reaction only, and the substrate specificity was correlated to one amino acid substitution. Detailed sequence analysis revealed the lack of the disulphide bond S1 (C78 and C323 in the SMT (sinapoylglucose:malate sinapoyltransferase), that is in SST C80 and D327). The reconstitution of this disulphide bond led to an enzyme accepting many different substrates including disaccharides. Interestingly, the overall changes within the model structures are not very dramatic, but nevertheless, the enzyme models provide some explanations for the broadened substrate specificity: the reconstitution of the disulphide bond provoked more space within the substrate binding pocket simultaneously avoiding electrostatic repulsion. As the SST sequence of A. lyrata also showed the same mutation, the loss of the disulphide bond should has arisen at least 10 mya ago. A Ka/Ks ratio ≤ 1 supports the hypothesis that the loss of this disulphide bond was rather a specification towards a certain reaction than the beginning of a gene death. At the same time, this is also associated with the fixation in the genome.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1350
TI  - Natural products - modifying metabolite pathways in plants
JO  - Biotechnol. J.
PY  - 2013
SP  - 1159-1171
AU  - Staniek, A.
AU  - Bouwmeester, H.
AU  - Fraser, P. D.
AU  - Kayser, O.
AU  - Martens, S.
AU  - Tissier, A.
AU  - van der Krol, S.
AU  - Wessjohann, L.
AU  - Warzecha, H.
AU  - 
VL  - 8
UR  - 
DO  - 10.1002/biot.201300224
AB  - The diversity of plant natural product (PNP) molecular structures is reflected in the variety of biochemical and genetic pathways that lead to their formation and accumulation. Plant secondary metabolites are important commodities, and include fragrances, colorants, and medicines. Increasing the extractable amount of PNP through plant breeding, or more recently by means of metabolic engineering, is a priority. The prerequisite for any attempt at metabolic engineering is a detailed knowledge of the underlying biosynthetic and regulatory pathways in plants. Over the past few decades, an enormous body of information about the biochemistry and genetics of biosynthetic pathways involved in PNPs production has been generated. In this review, we focus on the three large classes of plant secondary metabolites: terpenoids (or isoprenoids), phenylpropanoids, and alkaloids. All three provide excellent examples of the tremendous efforts undertaken to boost our understanding of biosynthetic pathways, resulting in the first successes in plant metabolic engineering. We further consider what essential information is still missing, and how future research directions could help achieve the rational design of plants as chemical factories for high‐value products.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1349
TI  - Multidimensional nano-HPLC coupled with tandem mass spectrometry for analyzing biotinylated proteins
JO  - Anal. Bioanal. Chem.
PY  - 2013
SP  - 2163-2173
AU  - Sproß, J.
AU  - Brauch, S.
AU  - Mandel, F.
AU  - Wagner, M.
AU  - Buckenmaier, S.
AU  - Westermann, B.
AU  - Sinz, A.
AU  - 
VL  - 405
UR  - 
DO  - 10.1007/s00216-012-6057-9
AB  - Multidimensional high-performance liquid chromatography (HPLC) is a key method in shotgun proteomics approaches for analyzing highly complex protein mixtures by complementary chromatographic separation principles. Here, we describe an integrated 3D-nano-HPLC/nano-electrospray ionization quadrupole time-of-flight mass spectrometry system that allows an enzymatic digestion of proteins followed by an enrichment and subsequent separation of the created peptide mixtures. The online 3D-nano-HPLC system is composed of a monolithic trypsin reactor in the first dimension, a monolithic affinity column with immobilized monomeric avidin in the second dimension, and a reversed phase C18 HPLC-Chip in the third dimension that is coupled to a nano-ESI-Q-TOF mass spectrometer. The 3D-LC/MS setup is exemplified for the identification of biotinylated proteins from a simple protein mixture. Additionally, we describe an online 2D-nano-HPLC/nano-ESI-LTQ-Orbitrap-MS/MS setup for the enrichment, separation, and identification of cross-linked, biotinylated species from chemical cross-linking of cytochrome c and a calmodulin/peptide complex using a novel trifunctional cross-linker with two amine-reactive groups and a biotin label.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1348
TI  - Striking stabilization of Rana catesbeiana ribonuclease 3 by guanidine hydrochloride
JO  - FEBS Lett.
PY  - 2013
SP  - 737-742
AU  - Solé, M.
AU  - Brandt, W.
AU  - Arnold, U.
AU  - 
VL  - 587
UR  - 
DO  - 10.1016/j.febslet.2013.01.056
AB  - Unfolding by chemical denaturants and the linear extrapolation method are widely used to determine the free energy of proteins. Ribonuclease 3 from bullfrog shows an extraordinary behavior in guanidinium hydrochloride in comparison to its homologues ribonuclease A and onconase with a high transition midpoint of denaturation but an apparently low cooperativity. The analysis of the interdependence of thermal, urea‐, and guanidine hydrochloride‐induced unfolding revealed that whereas addition of urea resulted in the expected destabilization of all three proteins, guanidine hydrochloride acted diversely: in contrast to ribonuclease A and onconase, both of which were destabilized as expected, low concentrations of guanidine hydrochloride significantly stabilize ribonuclease 3 from bullfrog. This stabilizing effect was endorsed by in silico docking studies.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1343
TI  - RDC-Based Determination of the Relative Configuration of the Fungicidal Cyclopentenone 4,6-Diacetylhygrophorone A12
JO  - J. Nat. Prod.
PY  - 2013
SP  - 839-844
AU  - Schmidts, V.
AU  - Fredersdorf, M.
AU  - Lübken, T.
AU  - Porzel, A.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - Thiele, C. M.
AU  - 
VL  - 76
UR  - 
DO  - 10.1021/np300728b
AB  - The hygrophorones, a class of cyclopentenones isolated from fruiting bodies of the genus Hygrophorus (basidiomycetes), show promising antifungal activity. While the constitution of 4,6-diacetylhygrophorone A(12) (3) and the relative configuration of the stereogenic centers in the cyclopentenone ring were elucidated using standard NMR and MS techniques, the relative configuration of the exocyclic stereogenic center could not be assigned. By introducing a sample of 3 into an alignment medium and measuring anisotropic NMR parameters, namely, residual dipolar couplings, we were able to unambiguously determine the relative configuration of all three stereogenic centers in 4,6-diacetylhygrophorone A(12) simultaneously by fitting several structure proposals to the experimental data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1339
TI  - A Multiple Multicomponent Approach to Chimeric Peptide-Peptoid Podands
JO  - Chem.-Eur. J.
PY  - 2013
SP  - 6417-6428
AU  - Rivera, D. G.
AU  - León, F.
AU  - Concepción, O.
AU  - Morales, F. E.
AU  - Wessjohann, L. A.
AU  - 
VL  - 19
UR  - 
DO  - 10.1002/chem.201201591
AB  - The success of multi‐armed, peptide‐based receptors in supramolecular chemistry traditionally is not only based on the sequence but equally on an appropriate positioning of various peptidic chains to create a multivalent array of binding elements. As a faster, more versatile and alternative access toward (pseudo)peptidic receptors, a new approach based on multiple Ugi four‐component reactions (Ugi‐4CR) is proposed as a means of simultaneously incorporating several binding and catalytic elements into organizing scaffolds. By employing α‐amino acids either as the amino or acid components of the Ugi‐4CRs, this multiple multicomponent process allows for the one‐pot assembly of podands bearing chimeric peptide–peptoid chains as appended arms. Tripodal, bowl‐shaped, and concave polyfunctional skeletons are employed as topologically varied platforms for positioning the multiple peptidic chains formed by Ugi‐4CRs. In a similar approach, steroidal building blocks with several axially‐oriented isocyano groups are synthesized and utilized to align the chimeric chains with conformational constrains, thus providing an alternative to the classical peptido‐steroidal receptors. The branched and hybrid peptide–peptoid appendages allow new possibilities for both rational design and combinatorial production of synthetic receptors. The concept is also expandable to other multicomponent reactions.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1335
TI  - The UBIAD1 Prenyltransferase Links Menaquinone-4 Synthesis to Cholesterol Metabolic Enzymes
JO  - Hum. Mutat.
PY  - 2013
SP  - 317-329
AU  - Nickerson, M. L.
AU  - Bosley, A. D.
AU  - Weiss, J. S.
AU  - Kostiha, B. N.
AU  - Hirota, Y.
AU  - Brandt, W.
AU  - Esposito, D.
AU  - Kinoshita, S.
AU  - Wessjohann, L.
AU  - Morham, S. G.
AU  - Andresson, T.
AU  - Kruth, H. S.
AU  - Okano, T.
AU  - Dean, M.
AU  - 
VL  - 34
UR  - 
DO  - 10.1002/humu.22230
AB  - Schnyder corneal dystrophy (SCD) is an autosomal dominant disease characterized by germline variants in UBIAD1 introducing missense alterations leading to deposition of cholesterol in the cornea, progressive opacification, and loss of visual acuity. UBIAD1 was recently shown to synthesize menaquinone‐4 (MK‐4, vitamin K2), but causal mechanisms of SCD are unknown. We report a novel c.864G&gt;A UBIAD1 mutation altering glycine 177 to glutamic acid (p.G177E) in six SCD families, including four families from Finland who share a likely founder mutation. We observed reduced MK‐4 synthesis by UBIAD1 altered by SCD mutations p.N102S, p.G177R/E, and p.D112N, and molecular models showed p.G177‐mutant UBIAD1 disrupted transmembrane helices and active site residues. We show UBIAD1 interacts with HMGCR and SOAT1, enzymes catalyzing cholesterol synthesis and storage, respectively, using yeast two‐hybrid screening and immunoprecipitation. Docking simulations indicate cholesterol binds to UBIAD1 in the substrate‐binding cleft and substrate‐binding overlaps with GGPP binding, an MK‐4 substrate, suggesting potential competition between these metabolites. Impaired MK‐4 synthesis is a biochemical defect identified in SCD suggesting UBIAD1 links vitamin K and cholesterol metabolism through physical contact between enzymes and metabolites. Our data suggest a role for endogenous MK‐4 in maintaining cornea health and visual acuity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1338
TI  - Protein modeling and molecular dynamic studies of two new surfactant proteins
JO  - J. Cheminform.
PY  - 2013
SP  - O2
AU  - Rausch, F.
AU  - Brandt, W.
AU  - Schicht, M.
AU  - Bräuer, L.
AU  - Paulsen, F.
AU  - 
VL  - 5
UR  - 
DO  - 10.1186/1758-2946-5-S1-O2
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 83
TI  - Virtual screening - tools for a faster selection of new drug leads
T2  - Medicinal Chemistry in Drug Discovery. Design, Synthesis and Screening
PB  - 
PY  - 2013
SP  - 219-236
AU  - Tennstedt, S.
AU  - Fischer, J.
AU  - Brandt, W.
AU  - Wessjohann, L.
AU  - 
VL  - 
UR  - 
AB  - Successful results in the fields of genomic, proteomic, and metabolomic research pave the way to thousands of protein sequences, many of which may be new clinical targets. The experimental effort to test millions of compounds for a large number of yet invalidated targets is very expensive. In the last decades, virtual screening has become an attractive alternative to precede experimental screening procedures, and thereby to reduce costs considerably. Virtual screening procedures show an enormous potential to suggest new hits and eventually lead structures. The concepts and methods to achieve such predictions are briefly summarized in this chapter. In principle, there are two strategies: if a protein structure is available, protein structure-based virtual screening is possible; the other alternative is ligand-based virtual screening. In recent years, the number of methods developed and software packages available for these tasks has increased considerably. The methods range from unspecific filtering procedures to pharmacophore searches, docking, and scoring. The most relevant current challenges, the limitations, and further perspectives for virtual screening in medicinal chemistry are discussed.
A2  - Jelić, D., ed.
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1399
TI  - Volatiles Profiling in Medicinal Licorice Roots Using Steam Distillation and Solid-Phase Microextraction (SPME) Coupled to Chemometrics
JO  - J. Food Sci.
PY  - 2012
SP  - C1179-C1184
AU  - Farag, M. A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 77
UR  - 
DO  - 10.1111/j.1750-3841.2012.02927.x
AB  - Abstract:  Licorice (Glycyrrhiza glabra L.) is a plant of considerable commercial importance in traditional medicine and for the flavor and sweets industry. Although Glycyrrhiza species are very competitive targets for phytochemical studies, very little is known about the volatiles composition within that genus, although such knowledge can be suspected to be relevant for understanding the olfactory and taste properties. To provide insight into Glycyrrhiza species aroma composition and for its use in food and pharmaceutical industry, volatile constituents from G. glabra, G. inflata, and G. echinata roots were profiled using steam distillation and solid‐phase microextraction. Two phenols, thymol and carvacrol, were found exclusively in essential oil and headspace samples of G. glabra, and with highest amounts for samples that originated from Egypt. In G. echinata oil, (2E, 4E)‐decadienal (21%) and β‐caryophyllene oxide (24%) were found as main constituents, whereas 1α, 10α‐epoxyamorpha‐4‐ene (13%) and β‐dihydroionone (8%) predominated G. inflata. Principal component and hierarchical cluster analyses clearly separated G. echinata and G. inflata from G. glabra; with phenolics and aliphatic aldehydes contributing mostly for species segregation.Practical Application:  Licorice (Glycyrrhiza glabra) has large economic, nutritional, and medicinal values. The data presented in this article help in licorice quality control analysis to identify G. glabra from its closely allied species. The presence of thymol and carvacrol exclusively in G. glabra suggests that these volatiles could serve as chemotaxonomic markers and also might be considered as potentially relevant for taste.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1398
TI  - Metabolome Classification of Commercial Hypericum perforatum (St. John&#39;s Wort) Preparations via UPLC-qTOF-MS and Chemometrics
JO  - Planta Med.
PY  - 2012
SP  - 488-496
AU  - Farag, M. A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 78
UR  - 
DO  - 10.1055/s-0031-1298170
AB  - The growing interest in the efficacy of phytomedicines and herbal supplements but also the increase in legal requirements for safety and reliable contents of active principles drive the development of analytical methods for the quality control of complex, multicomponent mixtures as found in plant extracts of value for the pharmaceutical industry. Here, we describe an ultra-performance liquid chromatography method (UPLC) coupled with quadrupole time of flight mass spectrometry (qTOF-MS) measurements for the large scale analysis of H. perforatum plant material and its commercial preparations. Under optimized conditions, we were able to simultaneously quantify and identify 21 metabolites including 4 hyperforins, 3 catechins, 3 naphthodianthrones, 5 flavonoids, 3 fatty acids, and a phenolic acid. Principal component analysis (PCA) was used to ensure good analytical rigorousness and define both similarities and differences among Hypericum samples. A selection of batches from 9 commercially available H. perforatum products available on the German and Egyptian markets showed variable quality, particularly in hyperforins and fatty acid content. PCA analysis was able to discriminate between various preparations according to their global composition, including differentiation between various batches from the same supplier. To the best of our knowledge, this study provides the first approach utilizing UPLC-MS-based metabolic fingerprinting to reveal secondary metabolite compositional differences in Hypericum extract.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1397
TI  - Metabolite profiling and fingerprinting of commercial cultivars of Humulus lupulus L. (hop): a comparison of MS and NMR methods in metabolomics
JO  - Metabolomics
PY  - 2012
SP  - 492-507
AU  - Farag, M. A.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Wessjohann, L. A.
AU  - 
VL  - 8
UR  - 
DO  - 10.1007/s11306-011-0335-y
AB  - Hop (Humulus lupulus L. Cannabaceae) is an economically important crop. In addition to its role in beer brewing, its pharmaceutical applications have been of increasing importance in recent years. Bitter acids (prenylated polyketides), prenylflavonoids and essential oils, are the primary phytochemical components that account for hop medicinal value. An integrated approach utilizing nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques was used for the first large-scale metabolite profiling in Humulus lupulus. Resins and extracts prepared from 13 hop cultivars were analysed using NMR, liquid chromatography (LC)-MS and fourier transform ion cyclotron resonance (FTICR)-MS in parallel and subjected to principal component analysis (PCA). A one pot extraction method, compatible with both MS and NMR measurement was developed to help rule out effects due to differences in extraction protocols. Under optimised conditions, we were able to simultaneously quantify and identify 46 metabolites including 18 bitter acids, 12 flavonoids, 3 terpenes, 3 fatty acids and 2 sugars. Cultivars segregation in PCA plots generated from both LC-MS and NMR data were found comparable and mostly influenced by differences in bitter acids composition among cultivars. FTICR-MS showed inconsistent PCA loading plot results which are likely due to preferential ionisation and also point to the presence of novel isoprenylated metabolites in hop. This comparative metabolomic approach provided new insights for the complementariness and coincidence for these different technology platform applications in hop and similar plant metabolomics projects.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1396
TI  - Comparative metabolite profiling and fingerprinting of medicinal licorice roots using a multiplex approach of GC–MS, LC–MS and 1D NMR techniques
JO  - Phytochemistry
PY  - 2012
SP  - 60-72
AU  - Farag, M. A.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 76
UR  - 
DO  - 10.1016/j.phytochem.2011.12.010
AB  - Glycyrrhiza glabra, commonly known as licorice, is a popular herbal supplement used for the treatment of chronic inflammatory conditions and possesses anticancer and antiviral activities. This species contains a plethora of phytochemicals including terpenoids, saponins, flavonoids, polyamines and polysaccharides. The full complement of bioactive compounds has yet to be elucidated, a step necessary in order to explain its medicinal use. There are over 30 species in the Glycyrrhiza genus world-wide, most of which have been little characterized in terms of phytochemical or pharmacological properties. Here, large scale multi-targeted metabolic profiling and fingerprinting techniques were utilized to help gain a broader insight into Glycyrrhiza species chemical composition. UV, MS and NMR spectra of extracted components were connected with NMR, MS, and multivariate analyses data from Glycyrrhiza glabra, Glycyrrhiza uralensis, Glycyrrhiza inflata and Glycyrrhiza echinata. Major peaks in 1H NMR and MS spectra contributing to the discrimination among species were assigned as those of glycyrrhizin, 4-hydroxyphenyl acetic acid, and glycosidic conjugates of liquiritigenin/isoliquiritigenin. Primary metabolites profiling using GC–MS revealed the presence of cadaverine, an amino acid, exclusively found in G. inflata roots. Both LC–MS and NMR were found effective techniques in sample classification based on genetic and or geographical origin as revealed from derived PCA analysis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1392
TI  - Aus Pilzen isolierte Substanz gegen den Erreger der Kraut- und Knollenfäule
JO  - Kartoffelbau
PY  - 2012
SP  - 18-21
AU  - Eschen-Lippold, L.
AU  - Rosahl, S.
AU  - Westermann, B.
AU  - Arnold, N.
AU  - 
VL  - 63
UR  - https://www.dlg-agrofoodmedien.de/fileadmin/download/jahresindex/Kartoffelbau/IND_KB_2012.pdf
AB  - 
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions
ER  - 


TY  - JOUR
ID  - 1388
TI  - Phytochemical and allelopathic studies of Terminalia catappa L. (Combretaceae)
JO  - Biochem. Syst. Ecol.
PY  - 2012
SP  - 119-125
AU  - de Gouveia Baratelli, T.
AU  - Candido Gomes, A. C.
AU  - Wessjohann, L. A.
AU  - Machado Kuster, R.
AU  - Kato Simas, N.
AU  - 
VL  - 41
UR  - 
DO  - 10.1016/j.bse.2011.12.008
AB  - The allelopathic potential of Terminalia catappa L. Combretaceae fruits and leaves on Lactuca sativa L. (lettuce), Euphorbia heterophylla L. and Commelina benghalensis L. was studied. Bioassays indicated the highest activity for dichloromethane and ethyl-acetate fractions of ethanolic extracts from fruits, and the mean effective concentration (EC50) was determined. 2-Pentadecanone; vanillic, siringic, ferulic, p-coumaric, palmitic and stearic acids were characterized in the dichloromethane fraction, and 3,4,4′-tri-O-methyl ellagic acid and β-sitosterol-3-O-β-d-glucoside were isolated from it. No allelopathic effects were observed when the dichloromethane extracts of T. catappa fruit or leaf extracts were applied to the weeds E. heterophylla and C. benghalensis. Bioassays with seasonal sampling revealed an influence on the allelochemical potential of T. catappa. Considering the methodology adopted and the experimental results, the allelopathic activity of T. catappa seems to be related to the interaction of different groups of substances, some of them identified and characterized in this work.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1385
TI  - A combinatorial TIR1/AFB–Aux/IAA co-receptor system for differential sensing of auxin
JO  - Nat. Chem. Biol.
PY  - 2012
SP  - 477-485
AU  - Calderón Villalobos, L. I. A.
AU  - Lee, S.
AU  - De Oliveira, C.
AU  - Ivetac, A.
AU  - Brandt, W.
AU  - Armitage, L.
AU  - Sheard, L. B.
AU  - Tan, X.
AU  - Parry, G.
AU  - Mao, H.
AU  - Zheng, N.
AU  - Napier, R.
AU  - Kepinski, S.
AU  - Estelle, M.
AU  - 
VL  - 8
UR  - 
DO  - 10.1038/nchembio.926
AB  - The plant hormone auxin regulates virtually every aspect of plant growth and development. Auxin acts by binding the F-box protein transport inhibitor response 1 (TIR1) and promotes the degradation of the AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) transcriptional repressors. Here we show that efficient auxin binding requires assembly of an auxin co-receptor complex consisting of TIR1 and an Aux/IAA protein. Heterologous experiments in yeast and quantitative IAA binding assays using purified proteins showed that different combinations of TIR1 and Aux/IAA proteins form co-receptor complexes with a wide range of auxin-binding affinities. Auxin affinity seems to be largely determined by the Aux/IAA. As there are 6 TIR1/AUXIN SIGNALING F-BOX proteins (AFBs) and 29 Aux/IAA proteins in Arabidopsis thaliana, combinatorial interactions may result in many co-receptors with distinct auxin-sensing properties. We also demonstrate that the AFB5–Aux/IAA co-receptor selectively binds the auxinic herbicide picloram. This co-receptor system broadens the effective concentration range of the hormone and may contribute to the complexity of auxin response.
A2  - 
C1  - Molecular Signal Processing; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1383
TI  - Fast and efficient MCR-based synthesis of clickable rhodamine tags for protein profiling
JO  - Org. Biomol. Chem.
PY  - 2012
SP  - 958-965
AU  - Brauch, S.
AU  - Henze, M.
AU  - Osswald, B.
AU  - Naumann, K.
AU  - Wessjohann, L. A.
AU  - van Berkel, S. S.
AU  - Westermann, B.
AU  - 
VL  - 10
UR  - 
DO  - 10.1039/C1OB06581E
AB  - Protein profiling probes are important tools for studying the composition of the proteome and as such have contributed greatly to the understanding of various complex biological processes in higher organisms. For this purpose the application of fluorescently labeled activity or affinity probes is highly desirable. Especially for in vivodetection of low abundant target proteins, otherwise difficult to analyse by standard blotting techniques, fluorescently labeled profiling probes are of high value. Here, a one-pot protocol for the synthesis of activated fluorescent labels (i.e.azide, alkynyl or NHS), based on the Ugi-4-component reaction (Ugi-4CR), is presented. As a result of the peptoidic structure formed, the fluorescent properties of the products are pH insensitive. Moreover, the applicability of these probes, as exemplified by the labeling of model protein BSA, will be discussed.
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions
ER  - 


TY  - JOUR
ID  - 1380
TI  - Synthesis, Characterization, and Reactivity of Diacetylplatinum(II) and -platinum(IV) Complexes Bearing κ2- and κ3-Coordinated Scorpionate Ligands
JO  - Organometallics
PY  - 2012
SP  - 3700-3710
AU  - Bette, M.
AU  - Rüffer, T.
AU  - Bruhn, C.
AU  - Schmidt, J.
AU  - Steinborn, D.
AU  - 
VL  - 31
UR  - 
DO  - 10.1021/om3001907
AB  - Reactions of the dinuclear platina-β-diketone [Pt2{(COR)2H}2(μ-Cl)2] (1) with K[(pz)3BH] and K[(3,5-Me2pz)3BH] (pz = pyrazolyl; 3,5-Me2pz = 3,5-dimethylpyrazolyl) afforded neutral diacetyl(hydrido)platinum(IV) complexes [Pt(COMe)2H{(pz)3BH}] (4a) and [Pt(COMe)2H{(3,5-Me2pz)3BH}] (4b), bearing κ3-bonded tris(pyrazolyl)borate (scorpionate) ligands. These complexes were found to decompose in chloroform solution under formation of the respective chlorido complexes [Pt(COMe)2Cl{(pz)3BH}] (5a) and [Pt(COMe)2Cl{(3,5-Me2pz)3BH}] (5b) as the initial step. Diacetylplatinum(II) complexes with κ2-coordinated scorpionate ligands (K[Pt(COMe)2{(pz)3BH}], 6a; K[Pt(COMe)2{(3,5-Me2pz)3BH}], 6b; K[Pt(COMe)2{(pz)4B}], 7; K[{Pt(COMe)2}2{(pz)4B}], 8) were obtained in ligand exchange reactions of [Pt(COMe)2(NH2Bn)2] (3; Bn = benzyl) with the respective potassium (pyrazolyl)borates. The deprotonation of the hydrido complexes 4 with potassium methoxide led also to the formation of 6. Diacetylplatinum(II) complexes 6a and 7 were found to react in oxidative addition reactions with alkyl halides to yield diacetylplatinum(IV) complexes of the type [Pt(COMe)2R{(pz)3BH)}] (R = Me, 9a; Et, 9b; Bn, 9c) and [Pt(COMe)2R{(pz)4B}] (R = Me, 10a; Et, 10b; Bn, 10c), respectively, with κ3-bonded scorpionate ligands. The identities of all platinum complexes were unambiguously proved by microanalyses or by high-resolution mass spectrometric investigations, by NMR (1H, 13C, 195Pt) and IR spectroscopies, and by single-crystal X-ray diffraction analyses (4a, 5a, 7·(18C6), 9c; 18C6 = 18-crown-6). The reactivity of the complexes is discussed in terms of hemilability of the scorpionate ligands.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1378
TI  - Analysis of cytokinin nucleotides by capillary zone electrophoresis with diode array and mass spectrometric detection in a recombinant enzyme in vitro reaction
JO  - Anal. Chim. Acta
PY  - 2012
SP  - 176-181
AU  - Béres, T.
AU  - Gemrotová, M.
AU  - Tarkowski, P.
AU  - Ganzera, M.
AU  - Maier, V.
AU  - Friedecký, D.
AU  - Dessoy, M. A.
AU  - Wessjohann, L. A.
AU  - Spíchal, L.
AU  - Strnad, M.
AU  - Doležal, K.
AU  - 
VL  - 751
UR  - 
DO  - 10.1016/j.aca.2012.08.049
AB  - A capillary zone electrophoresis (CZE) method for separation of adenosine and N6-isopentenyladenosine (cytokinin) nucleotides was developed, optimized and validated. Aqueous solutions of several amino acids were evaluated as the background electrolyte constituents. Separation of six nucleotides in less than 20 min with high theoretical plate number (up to 400 000 for isopentenyladenosine triphosphate) was achieved using a 100 mM sarcosine/ammonia buffer at pH 10.0. The detection limits of the CZE-UV method are in the low micromolar range (0.69–1.27 μmol L−1). Good repeatability of migration times (within 1.3%), peak areas (within 1.8%) and linearity (R2 &gt; 0.999) was achieved over the concentration range 5–1000 μmol L−1. The method was used to assay the activity of the recombinant Arabidopsis thaliana isopentenyltransferase 1 (AtIPT1). Baseline separation of isopentenylated nucleotides by CE–ESI-MS using a volatile buffer (30 mM ammonium formate; pH 10.0) was accomplished. The identities of the reaction products – isopentenyladenosine di- and triphosphate were confirmed by HPLC-QqTOF-MS. Dephosphorylation of ATP was observed as a parallel reaction.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1374
TI  - CHEMISTRY OF THE AROMA BOUQUET OF THE EDIBLE MUSHROOM "LEBRE" (Cortinarius lebre, BASDIOMYCOTA, AGARICALES) FROM CHILE
JO  - J. Chil. Chem. Soc.
PY  - 2012
SP  - 1333-1335
AU  - Arnold, N.
AU  - Palfner, G.
AU  - Schmidt, J.
AU  - Kuhnt, C.
AU  - Becerra, J.
AU  - 
VL  - 57
UR  - 
DO  - 10.4067/S0717-97072012000300029
AB  - Cortinarius lebre Garrido, a common edible mushroom from central Chile, is distinct from other Cortinarii by its strong, naphtalene-like smell. The relevant volatile compounds were detected by gas chromatography - mass spectrometry and identified as indole together with 1-octen-3-ol, octane-3-one, and octan-3-ol.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1465
TI  - Basidiomycetous Yeasts from Boletales Fruiting Bodies and Their Interactions with the Mycoparasite Sepedonium chrysospermum and the Host Fungus Paxillus
JO  - Microb. Ecol.
PY  - 2012
SP  - 295-303
AU  - Yurkov, A.
AU  - Krüger, D.
AU  - Begerow, D.
AU  - Arnold, N.
AU  - Tarkka, M. T.
AU  - 
VL  - 63
UR  - 
DO  - 10.1007/s00248-011-9923-7
AB  - Interactions between mushrooms, yeasts, and parasitic fungi are probably common in nature, but are rarely described. Bolete fruiting bodies are associated with a broad spectrum of microorganisms including yeasts, and they are commonly infected with filamentous mycoparasites of the genus Sepedonium (teleomorph Hypomyces). We report the isolation of 17 yeast strains from Paxillus and Xerocomus, 16 of which were obtained from the surface tissue, the primary site of Sepedonium infection. Phylogenetic analyses with the D1/D2 region of the 28S ribosomal gene and the internal transcribed spacers placed the yeasts as Rhodotorula, Rhodosporidium, and Mastigobasidium from the Pucciniomycotina, Cryptococcus, Cystofilobasidium, Holtermanniella, and Trichosporon from the Agaricomycotina, and Kluyveromyces from the Saccharomycotina including the first isolation of Rhodotorula graminis from Europe. To investigate the influence of the yeast strains on the mycoparasite and the host fungus, in vitro assays were conducted with Sepedonium chrysospermum and Paxillus involutus. Both S. chrysospermum growth inhibitory and stimulating yeast strains were detected among the isolates. The number of S. chrysospermum inhibitory yeast strains increased and the number of S. chrysospermum stimulatory yeast strains decreased in the presence of P. involutus in co-cultures. Low nutrient levels in the culture medium also led to an increased number of S. chrysospermum inhibitory yeast strains and ten yeasts inhibited the mycoparasite in spatial separation by a crosswall. Six yeast strains inhibited P. involutus in dual culture, and the inhibitory P. involutus yeast interactions increased to nine in the presence of S. chrysospermum. Our results suggest that the bolete-associated yeasts influence the growth of the mycoparasitic fungus, which may affect the health of the fruiting bodies.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1464
TI  - Compositional and structural studies of the oils from two edible seeds: Tiger nut, Cyperus esculentum, and asiato, Pachira insignis, from Ghana
JO  - Food Res. Int.
PY  - 2012
SP  - 259-266
AU  - Yeboah, S. O.
AU  - Mitei, Y. C.
AU  - Ngila, J. C.
AU  - Wessjohann, L.
AU  - Schmidt, J.
AU  - 
VL  - 47
UR  - 
DO  - 10.1016/j.foodres.2011.06.036
AB  - A comprehensive lipid profiling has been carried out on the seed oils of tiger nut, Cyperus esculentum, and asiato, Pachira insignis, from Ghana in order to evaluate their potential uses for the region. Composition of FAs and phytosterols were determined using GC–MS, while tocol composition was determined with HPLC. TAG composition and regiochemistry were determined using ES-FTICR-MS and 13C NMR, respectively. The major FA components in asiato seed oil were palmitic acid (56.58%) and sterculic and dihydrosterculic acids (20.06% combined). The major FA components in tiger nut oil were oleic (65.55%), palmitic (16. 32%), and linoleic (12.13%) acids. Asiato seed oil had 18 major TAG classes, dominated by, C51:1 (38.45%) and C50:1 (13.941%). Tiger nut oil had 7 major TAG classes, with C54:3 (29.00%) and C52:2 (27.82%) dominating. The sn-1/3 and sn-2 positions in the TAGS for asiato oil were predominantly occupied by saturated acyl chains (87.25%) and cyclic acyl chains (71.44%), respectively. Oleoyl chain primarily occupied both sn-1/3 (52.68%) and sn-2 (77.62%) positions in the tiger nut oil. Total tocol content in asiato oil was 200.31 μg/g, with γ-tocopherol (182.99 μg/g) dominating. Tiger nut oil had a total tocol content of 120.10 μg/g, dominated by α-tocopherol (86.73) and β-tocopherol (33.37 μg/g).Tiger nut oil had total 4-desmethylsterol content of 986 μg/g, dominated by β-sitosterol (517.25 μg/g) and stigmasterol (225.25 μg/g), while asiato oil had total desmethylsterol content of 590.24 μg/g, dominated by β-sitosterol (518.91 μg/g). The presence of cyclopropenoid FAs in asiato oil makes it unsuitable for food uses. Tiger nut oil can replace imported olive oil in food products in the West African region.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1461
TI  - Prenyl- und Methyltransferasen in Natur und Synthese
JO  - BIOspektrum
PY  - 2012
SP  - 22-25
AU  - Wessjohann, L.
AU  - Vogt, T.
AU  - Kufka, J.
AU  - Klein, R.
AU  - 
VL  - 18
UR  - 
DO  - 10.1007/s12268-012-0137-4
AB  - Late stage enzymatic prenylation and methylation are means to diversify (natural) compounds and to specify their functions. In eukaryotes and microbes, these steps are performed by large enzyme families, the prenyl and methyl transferases, which modify various types of small molecules, like isoprenoids, phenolics or alkaloids, but also DNA and proteins. We investigate the theoretical basis of these processes and possible commercial applications in synthetic chemistry.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1459
TI  - Palladium and copper catalyzed cyclizations of hydrazine derived Ugi products: facile synthesis of substituted indazolones and hydroxytriazafluorendiones
JO  - Tetrahedron Lett.
PY  - 2012
SP  - 2298-2301
AU  - Welsch, S. J.
AU  - Kalinski, C.
AU  - Umkehrer, M.
AU  - Ross, G.
AU  - Kolb, J.
AU  - Burdack, C.
AU  - Wessjohann, L. A.
AU  - 
VL  - 53
UR  - 
DO  - 10.1016/j.tetlet.2012.02.095
AB  - Indazolones are medicinally relevant targets. Herein we disclose an improved synthesis to N′-(acetamido-2-yl)-substituted indazolones with four points of diversity introduced by Ugi-[M]-amination and -amidation. The ring closure can be achieved by either conventional palladium catalysis or with a ligandless copper protocol. When α-unbranched isocyanides were employed the sole cyclization products of the copper catalyzed reactions are the hitherto undescribed 2-hydroxy-3H-3,4a,9a-triaza-fluorene-4,9-diones.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1453
TI  - “Spurlose” Tosylhydrazon-basierte Triazolsynthese: eine metallfreie Alternative zur ringspannungskatalysierten Azid-Alkin-Cycloaddition
JO  - Angew. Chem.
PY  - 2012
SP  - 5437-5441
AU  - van Berkel, S. S.
AU  - Brauch, S.
AU  - Gabriel, L.
AU  - Henze, M.
AU  - Stark, S.
AU  - Vasilev, D.
AU  - Wessjohann, L. A.
AU  - Abbas, M.
AU  - Westermann, B.
AU  - 
VL  - 124
UR  - 
DO  - 10.1002/ange.201108850
AB  - Durch Reaktion primärer Amine mit funktionalisierten α,α‐Dichlortosylhydrazonen unter milden Bedingungen gelingt eine „spurlose“ Tosylhydrazon‐basierte Triazolsynthese, die ausschließlich zur Bildung 1,4‐substituierter Triazol‐„Klick‐Produkte“ unter vollständigem Konfigurationserhalt am Stereozentrum führt. Primäre Amine, die in vielen Naturstoffen vorkommen, können chemoselektiv ohne die Notwendigkeit einer umfassenden Schutzgruppenstrategie modifiziert werden.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1452
TI  - Traceless Tosylhydrazone-Based Triazole Formation: A Metal-Free Alternative to Strain-Promoted Azide-Alkyne Cycloaddition
JO  - Angew. Chem. Int. Ed.
PY  - 2012
SP  - 5343-5346
AU  - van Berkel, S. S.
AU  - Brauch, S.
AU  - Gabriel, L.
AU  - Henze, M.
AU  - Stark, S.
AU  - Vasilev, D.
AU  - Wessjohann, L. A.
AU  - Abbas, M.
AU  - Westermann, B.
AU  - 
VL  - 51
UR  - 
DO  - 10.1002/anie.201108850
AB  - Triple‐T trick! Traceless tosylhydrazone‐based triazole formation is readily achieved by reacting primary amines with functional α,α‐dichlorotosylhydrozones under ambient conditions. This fast and efficient alternative affords exclusively 1,4‐substituted triazole “click products” with complete retention of configuration. Primary amines, inherent to many natural products, can be modified in this way without protecting group manipulations.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1451
TI  - Recent Advances in Asymmetric Isocyanide-Based Multicomponent Reactions
JO  - Eur. J. Org. Chem.
PY  - 2012
SP  - 3543-3559
AU  - van Berkel, S. S.
AU  - Bögels, B. G. M.
AU  - Wijdeven, M. A.
AU  - Westermann, B.
AU  - Rutjes, F. P. J. T.
AU  - 
VL  - 2012
UR  - 
DO  - 10.1002/ejoc.201200030
AB  - This review discusses the use of various isocyanides (regular, chiral, and convertible) in asymmetric multicomponent reactions. In particular, stereoselective Ugi and Passerini reactions are highlighted, as well as their applications in modular sequential reactions and natural product synthesis.Isocyanide‐based multicomponent reactions (IMCRs) can be considered one of the breakthrough reaction classes of the last century. Moreover, asymmetric IMCRs have recently developed into powerful reactions for the versatile synthesis of highly complex molecules. The progress made in the development of stereoselective Passerini and Ugi reactions has led to the advancement of catalytic asymmetric IMCRs. This review gives an overview of recent advances in the field of asymmetric IMCRs with a focus on stereoselective α‐additions of isocyanides. In addition, the use of convertible isocyanides in stereoselective cascade IMCRs is covered and future opportunities and potential applications of (asymmetric) IMCRs are briefly discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1448
TI  - Characterization of Constituents and Anthelmintic Properties of Hagenia abyssinica
JO  - Sci. Pharm.
PY  - 2012
SP  - 433-446
AU  - Thomsen, H.
AU  - Reider, K.
AU  - Franke, K.
AU  - Wessjohann, L. A.
AU  - Keiser, J.
AU  - Dagne, E.
AU  - Arnold, N.
AU  - 
VL  - 80
UR  - 
DO  - 10.3797/scipharm.1109-04
AB  - The dried female flowers of Hagenia abyssinica (Bruce) J. F. Gmel. (Rosaceae) are traditionally used as an anthelmintic remedy in Ethiopia and formerly were incorporated into the European Pharmacopoeia. One-, two- and tricyclic phloroglucinol derivatives (kosins) were suggested to be the active principles. However, polar constituents may also contribute to the activity. Therefore, we investigated for the first time the polar constituents. We isolated typical Rosaceae constituents such as quercetin 3-O-β-glucuronide, quercetin 3-O-β-glucoside and rutin. Polar kosin glycosides or derivatives could not be detected.The anthelmintic activity of fractions of different polarity were tested against the blood fluke Schistosoma mansoni, the liver flukes Clonorchis sinensis and Fasciola hepatica and the intestinal fluke Echinostoma caproni. The anthelmintic activity decreased with increasing polarity of the tested fractions. ESI-MS investigations indicated the predominant occurrence of kosins in the active fractions.Using the anthelmintic active extracts of Hagenia abyssinica we developed a simple, inexpensive bioassay against the non-parasitic nematode Caenorhabditis elegans, which can be used as an initial screening procedure for anthelmintic properties of crude extracts of plants or fungi. The anthelmintic activity of test extracts against the model organism was determined in a microtiter plate assay by enumeration of living and dead nematodes under a microscope.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1447
TI  - Triterpene acids and polyphenols from Eriobotrya poilanei
JO  - Biochem. Syst. Ecol.
PY  - 2012
SP  - 198-200
AU  - Thien, D. G.
AU  - Hoang Anh, N. T.
AU  - Porzel, A.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - Van Sung, T.
AU  - 
VL  - 40
UR  - 
DO  - 10.1016/j.bse.2011.11.001
AB  - The occurrence of flavolignans might be a valuable chemotaxonomic marker for the classification of Rosaceae species.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1446
TI  - Helicascolide C, a new lactone from an Indonesian marine algicolous strain of Daldinia eschscholzii (Xylariaceae, Ascomycota)
JO  - Phytochem. Lett.
PY  - 2012
SP  - 83-86
AU  - Tarman, K.
AU  - Palm, G. J.
AU  - Porzel, A.
AU  - Merzweiler, K.
AU  - Arnold, N.
AU  - Wessjohann, L. A.
AU  - Unterseher, M.
AU  - Lindequist, U.
AU  - 
VL  - 5
UR  - 
DO  - 10.1016/j.phytol.2011.10.006
AB  - From an endophytic Daldinia eschscholzii strain isolated from the agar-producing red alga Gracilaria sp. SGR-1, collected from the coast of South Sulawesi, Indonesia, a new lactone helicascolide C (1) was obtained as colourless crystals from the ethyl acetate extract together with the related structurally known compound helicascolide A (2). The structure of the new compound 1 reveals a carbonyl group replacing an alcohol group of compound 2. The structure of 1 was elucidated by X-ray diffraction and spectral analyses. Compound 1 showed fungistatic activity against the phytopathogenic fungus Cladosporium cucumerinum.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1440
TI  - Comparison of Impurity Profiles of Lipiblock® vs. Orlistat using HPLC and LC-MS/MS
JO  - Lat. Am. J. Pharm.
PY  - 2012
SP  - 91-96
AU  - Schneider, A.
AU  - Wessjohann, L. A.
AU  - Severi, J. A.
AU  - Wagner, V.
AU  - 
VL  - 31
UR  - http://www.latamjpharm.org/previous_issue.php?vol=31&amp;num=1
AB  - Comparative HPLC-UV and LC-MS/MS studies of impurity profiles of a reference sample (Xenical®, F. Hoffmann–La Roche Ltd., Switzerland) vs. generic (Lipiblock®, EMS–Sigma Pharma, a generic drug) were carried out with ethanol extracts of commercial samples. The generic formulation contained higher levels of common impurities as well as a considerable number of impurities not found in the reference product. The detected impurity profile of Lipiblock® revealed that it most likely is based on fermentation. Since the effect of the impurities is unknown, at this point fully synthetic Xenical® appears to offer a better safety margin than Lipiblock® which, however, compares quite well to other generic formulations.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1439
TI  - Biosynthesis of the defensive alkaloid cicindeloine in Stenus solutus beetles
JO  - Naturwissenschaften
PY  - 2012
SP  - 665-669
AU  - Schierling, A.
AU  - Dettner, K.
AU  - Schmidt, J.
AU  - Seifert, K.
AU  - 
VL  - 99
UR  - 
DO  - 10.1007/s00114-012-0945-x
AB  - To protect themselves from predation and microorganismic infestation, rove beetles of the genus Stenus produce and store bioactive alkaloids like stenusine, 3-(2-methyl-1-butenyl)pyridine, and cicindeloine in their pygidial glands. The biosynthesis of stenusine and 3-(2-methyl-1-butenyl)pyridine was previously investigated in Stenus bimaculatus and Stenus similis, respectively. Both molecules follow the same biosynthetic pathway, where the N-heterocyclic ring is derived from l-lysine and the side chain from l-isoleucine. The different alkaloids are finally obtained by slight modifications of shared precursor molecules. The piperideine alkaloid cicindeloine occurs as a main compound additionally to (E)-3-(2-methyl-1-butenyl)pyridine and traces of stenusine in the pygidial gland secretion of Stenus cicindeloides and Stenus solutus. Feeding of S. solutus beetles with [D,15N]-labeled amino acids followed by GC/MS analysis techniques showed that cicindeloine is synthesized via the identical pathway and precursor molecules as the other two defensive alkaloids.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1372
TI  - Spontaneous Formation of Giant Bioactive Protein-Block Copolymer Vesicles in Water
JO  - ACS Macro Lett.
PY  - 2012
SP  - 1016-1019
AU  - Amado, E.
AU  - Schöps, R.
AU  - Brandt, W.
AU  - Kressler, J.
AU  - 
VL  - 1
UR  - 
DO  - 10.1021/mz300304u
AB  - A novel strategy for the formation, without the need for organic solvents, of stable giant proteopolymersomes from the highly water-soluble triblock copolymer poly(2,3-dihydroxypropyl methacrylate)-b-poly(propylene oxide)-b-poly(2,3-dihydroxypropyl methacrylate) and the protein assembly streptavidin (SAv)-biotin-bovine serum albumin is presented. The method yields bioactive polymersomes with sizes in the tens of micrometers range having an SAv-functionalized membrane, thus, offering binding sites for a broad range of biotin conjugates. The vesiculation mechanism and the distribution of polymer and proteins in the proteopolymersomes membrane are investigated by confocal laser scanning microscopy and supported by molecular dynamic simulations.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1371
TI  - Chemical Composition, Antimicrobial, Antiradical and Anticholinesterase activity of the Essential Oil of Pulicaria stephanocarpa from Soqotra
JO  - Nat. Prod. Commun.
PY  - 2012
SP  - 113-116
AU  - Ali, N. A. A.
AU  - Crouch, R. A.
AU  - Al-Fatimi, M. A.
AU  - Arnold, N.
AU  - Teichert, A.
AU  - Setzer, W. N.
AU  - Wessjohann, L.
AU  - 
VL  - 7
UR  - 
DO  - 10.1177/1934578X1200700137
AB  - The chemical composition of the hydrodistilled leaf essential oil from Pulicaria stephanocarpa Balf Fil was determined by GC-MS analysis, and its antimicrobial, antioxidant and anticholinesterase (AChE) activities were evaluated. Eighty-three compounds were identified representing 97.2% of the total oil. (E)-Caryophyllene 13.4%, (E)-nerolidol 8.5%, caryophyllene oxide 8.5%, α-cadinol 8.2% spathulenol 6.8% and τ-cadinol 4.7%, were the main components. Antimicrobial activity of the oil, evaluated using the disc diffusion and broth dilution methods, demonstrated the highest susceptibility on Gram-positive bacteria and Candida albicans. The free radical scavenging ability of the oil was assessed by the DPPH assay to show antiradical activity with IC50 of 330 μg/mL. Moreover, the oil revealed an AChE inhibitory activity of 47% at a concentration of 200 μg/mL using Ellman&#39;s method.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1370
TI  - Chemical Composition, Antimicrobial, Antioxidant and Cytotoxic Activity of Essential Oils of Plectranthus cylindraceus and Meriandra benghalensis from Yemen
JO  - Nat. Prod. Commun.
PY  - 2012
SP  - 1099-1102
AU  - Ali, N. A. A.
AU  - Wurster, M.
AU  - Denkert, A.
AU  - Arnold, N.
AU  - Fadail, I.
AU  - Al-Didamony, G.
AU  - Lindequist, U.
AU  - Wessjohann, L.
AU  - Setzer, W. N.
AU  - 
VL  - 7
UR  - 
DO  - 10.1177/1934578X1200700834
AB  - The chemical composition, antimicrobial, antioxidant and cytotoxic activities of the essential oils isolated from the leaves of Plectranthus cylindraceus Hoechst. ex. Benth. (EOPC) and Meriandra benghalensis (Roxb.) Benth. (EOMB) were investigated. Sixteen compounds were identified in P. cylindraceus oil representing 94.5% of the oil content with thymol (68.5%), terpinolene (5.3%), β-selinene (4.7%), β-caryophyllene (4.0%), δ-cadinol (2.1%), and ar-curcumene (1.7%) as the major compounds. In M. benghalensis oil, 12 compounds were identified, which made up 82.0% of the total oil. The most abundant constituents were camphor (43.6%), 1,8-cineole (10.7%), α-eudesmol (5.8%), caryophyllene oxide (5.8%), camphene (5.3%) and borneol (3.4%). The antimicrobial activities of both oils were evaluated against five microorganisms with the disc diffusion test, the broth micro-dilution method and a semiquantitative bioautographic test. The most sensitive microorganisms for P. cylindraceus oil were S. aureus, B. subtilis, and C. albicans with inhibition zones of 38, 42, and 43 mm and MIC values of 0.39, 0.18, and, 0.18 μL/mL, respectively. M. benghalensis oil showed weak to moderate activity against the tested microorganisms. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay was employed to study the potential antioxidant activities of both oils. The antioxidant activity of P. cylindraceus oil (IC50 34.5 μg/mL) appeared to be higher than that of M. benghalensis oil (IC50 935 μg/mL). At a concentration of 100 μg/mL, EOMB showed a stronger cytotoxic activity, with growth inhibition of 71% against HT29 tumor cells, than EOPC (18%).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1369
TI  - Chemical Composition and Biological Activity of Essential Oil from Pulicaria undulata from Yemen
JO  - Nat. Prod. Commun.
PY  - 2012
SP  - 257-260
AU  - Ali, N. A. A.
AU  - Sharopov, F. S.
AU  - Alhaj, M.
AU  - Hill, G. M.
AU  - Porzel, A.
AU  - Arnold, N.
AU  - Setzer, W. N.
AU  - Schmidt, J.
AU  - Wessjohann, L.
AU  - 
VL  - 7
UR  - 
DO  - 10.1177/1934578X1200700238
AB  - The chemical composition of the essential oil obtained from the leaves of Pulicaria undulata Gamal Ed Din (syn P. oriental sensu Schwartz and P. jaubertii Gamal Ed Din) was analyzed by GC-MS. Major compounds of P. undulata oil were the oxygenated monoterpenenes, carvotanacetone (91.4%) and 2,5-dimethoxy-p-cymene (2.6.%). The antimicrobial activity of the essential oil was evaluated against six microorganisms, Escherichia coli Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Candida albicans, using disc diffusion and broth microdilution methods. The oil showed the strongest bactericidal activity against Staphylococcus aureus and methicillin-resistant S. aureus, as well as Candida albicans. The essential oil showed moderate cytotoxic activity against MCF-7 breast tumor cells, with an IC50 of 64.6 ±13.7 μg/mL. Bioautographic assays were used to evaluate the acetylcholinesterase inhibitory effect as well as antifungal activity of the oil against Cladosporium cucumerinum.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1368
TI  - Direct synthesis of sensitive selenocysteine peptides by the Ugi reaction
JO  - Org. Biomol. Chem.
PY  - 2012
SP  - 9330-9333
AU  - Abbas, M.
AU  - Wessjohann, L. A.
AU  - 
VL  - 10
UR  - 
DO  - 10.1039/C2OB26552D
AB  - Ammonia and selenoaldehydes are both problematic components in Ugi reactions. Here we report the efficient direct multicomponent synthesis of sensitive selenocysteinepeptides without the use of convertible (protected) primary amines, including suitable deprotection protocols for selenols.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1433
TI  - “SP-G”, a Putative New Surfactant Protein – Tissue Localization and 3D Structure
JO  - PLOS ONE
PY  - 2012
SP  - e47789
AU  - Rausch, F.
AU  - Schicht, M.
AU  - Paulsen, F.
AU  - Ngueya, I.
AU  - Bräuer, L.
AU  - Brandt, W.
AU  - 
VL  - 7
UR  - 
DO  - 10.1371/journal.pone.0047789
AB  - Surfactant proteins (SP) are well known from human lung. These proteins assist the formation of a monolayer of surface-active phospholipids at the liquid-air interface of the alveolar lining, play a major role in lowering the surface tension of interfaces, and have functions in innate and adaptive immune defense. During recent years it became obvious that SPs are also part of other tissues and fluids such as tear fluid, gingiva, saliva, the nasolacrimal system, and kidney. Recently, a putative new surfactant protein (SFTA2 or SP-G) was identified, which has no sequence or structural identity to the already know surfactant proteins. In this work, computational chemistry and molecular-biological methods were combined to localize and characterize SP-G. With the help of a protein structure model, specific antibodies were obtained which allowed the detection of SP-G not only on mRNA but also on protein level. The localization of this protein in different human tissues, sequence based prediction tools for posttranslational modifications and molecular dynamic simulations reveal that SP-G has physicochemical properties similar to the already known surfactant proteins B and C. This includes also the possibility of interactions with lipid systems and with that, a potential surface-regulatory feature of SP-G. In conclusion, the results indicate SP-G as a new surfactant protein which represents an until now unknown surfactant protein class.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1432
TI  - Molekülsimulation von Surfactant-Proteinen
JO  - Ophthalmologische Nachrichten
PY  - 2012
SP  - 13
AU  - Rausch, F.
AU  - 
VL  - 12.2012
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1429
TI  - Flavonoids and a neolignan glucoside from Guarea macrophylla (Meliaceae)
JO  - Quím. Nova
PY  - 2012
SP  - 1123-1126
AU  - Pereira, C.
AU  - Barreto Júnior, C. B.
AU  - Kuster, R. M.
AU  - Simas, N. K.
AU  - Sakuragui, C. M.
AU  - Porzel, A.
AU  - Wessjohann, L.
AU  - 
VL  - 35
UR  - 
DO  - 10.1590/S0100-40422012000600010
AB  - This work describes the phytochemical study of the methanol extract obtained from leaves of Guarea macrophylla, leading to the isolation and identification of three flavonoid glycosides (quercetin 3-O-β-D-glucopyranoside, quercetin 3-O-b-D-galactopyranoside, kaempferol 7-O-β-D-glucopyranoside) and a neolignan glucoside, dehydrodiconiferyl alcohol-4-β-D-glucoside. All compounds were identified by a combination of spectroscopic methods (1H, 1D, 2D NMR, 13C and UV), ESI-MS and comparison with the literature data. This is the first report of flavonoids in the genus Guarea and of a neolignan glucoside in the Meliaceae family.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1424
TI  - The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues
JO  - Beilstein J. Org. Chem.
PY  - 2012
SP  - 2085-2090
AU  - Neves Filho, R. A. W.
AU  - Stark, S.
AU  - Westermann, B.
AU  - Wessjohann, L. A.
AU  - 
VL  - 8
UR  - 
DO  - 10.3762/bjoc.8.234
AB  - Two syntheses of natural viridic acid, an unusual triply N-methylated peptide with two anthranilate units, are presented. The first one is based on peptide-coupling strategies and affords the optically active natural product in 20% overall yield over six steps. A more economical approach with only four steps leads to the similarly active racemate by utilizing a Ugi four-component reaction (Ugi-4CR) as the key transformation. A small library of viridic acid analogues is readily available to provide first SAR insight. The biological activities of the natural product and its derivatives against the Gram-negative bacterium Aliivibrio fischeri were evaluated.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1423
TI  - Patented Catalysts for the Synthesis and Biological Applications of Dihydropyrimidinones: Recent Advances of the Biginelli Reaction
JO  - Recent Pat. Catal.
PY  - 2012
SP  - 51-73
AU  - Neves Filho, R. A. W.
AU  - Brauer, M. C. N.
AU  - Palm-Forster, M. A. T.
AU  - de Oliveira, R. N.
AU  - Wessjohann, L. A.
AU  - 
VL  - 1
UR  - 
DO  - 10.2174/2211548X11201010051
AB  - The acid-catalyzed and thermal multicomponent cyclocondensation between an aldehyde, a beta-keto ester and urea to generate dihydropyrimidinones (DHPMs) is one of the best studied multicomponent reactions in organic synthesis. It is frequently employed in the synthesis of natural products and biologically active compounds. After several years under academic development, this reaction drew the attention of researchers in the chemical and pharmaceutical industry. This critical review is focused on the development and applications of the Biginelli three component reaction (B-3CR) patented in the last three decades.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1422
TI  - 4-Isocyanopermethylbutane-1,1,3-triol (IPB): a convertible isonitrile for multicomponent reactions
JO  - Tetrahedron Lett.
PY  - 2012
SP  - 5360-5363
AU  - Neves Filho, R. A. W.
AU  - Stark, S.
AU  - Morejon, M. C.
AU  - Westermann, B.
AU  - Wessjohann, L. A.
AU  - 
VL  - 53
UR  - 
DO  - 10.1016/j.tetlet.2012.07.064
AB  - The synthesis and applications of 4-isocyanopermethylbutane-1,1,3-triol (IPB) as a new convertible isonitrile (isocyanide) for isocyanide-based multicomponent reactions (IMCRs) like Ugi, Ugi-Smiles, and Passerini reactions are described. The primary products obtained from these IMCRs can be converted into highly activated N-acylpyrroles, which upon treatment with nucleophiles can be transformed into carboxylic acids, esters, amides, alcohols, and olefins. In this sense the reagent can be seen as a neutral carbanion equivalent to formate (HO2C−), and carboxylates or carboxamides etc. (RNu-CO−).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1421
TI  - New cardiolipin analogs synthesized by phospholipase D-catalyzed transphosphatidylation
JO  - Chem. Phys. Lipids
PY  - 2012
SP  - 787-793
AU  - Müller, A. O.
AU  - Mrestani-Klaus, C.
AU  - Schmidt, J.
AU  - Ulbrich-Hofmann, R.
AU  - Dippe, M.
AU  - 
VL  - 165
UR  - 
DO  - 10.1016/j.chemphyslip.2012.09.005
AB  - Cardiolipin (CL) and related diphosphatidyl lipids are hardly accessible because of the complexity of their chemical synthesis. In the present paper, the transphosphatidylation reaction catalyzed by phospholipase D (PLD) from Streptomyces sp. has been proven as an alternative enzyme-assisted strategy for the synthesis of new CL analogs. The formation of this type of compounds from phosphatidylcholine was compared for a series of N- and C2-substituted ethanolamine derivatives as well as non-charged alcohols such as glycerol and ethylene glycol. The rapid exchange of the choline head group by ethanolamine derivatives having a low molecular volume (diethanolamine and serinol) gave rise to an efficient production of the corresponding CL analogs. In contrast, the yields were comparably low in the reaction with bulky nitrogenous acceptor alcohols (triethanolamine, tris(hydroxymethyl)aminomethane, tetrakis(hydroxyethyl)ammonium) or the non-charged alcohols. Therefore, a strong dependence of the conversion of the monophosphatidyl to the diphosphatidyl compound on steric parameters and the head group charge was concluded. The enzyme-assisted strategy was used for the preparation of purified diphosphatidyldiethanolamine and diphosphatidylserinol.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1420
TI  - Identification of Enterodiol as a Masker for Caffeine Bitterness by Using a Pharmacophore Model Based on Structural Analogues of Homoeriodictyol
JO  - J. Agr. Food Chem.
PY  - 2012
SP  - 6303-6311
AU  - Ley, J. P.
AU  - Dessoy, M.
AU  - Paetz, S.
AU  - Blings, M.
AU  - Hoffmann-Lücke, P.
AU  - Reichelt, K. V.
AU  - Krammer, G. E.
AU  - Pienkny, S.
AU  - Brandt, W.
AU  - Wessjohann, L.
AU  - 
VL  - 60
UR  - 
DO  - 10.1021/jf301335z
AB  - Starting from previous structure–activity relationship studies of taste modifiers based on homoeriodictyol, dihydrochalcones, deoxybenzoins, and trans-3-hydroxyflavones as obvious analogues were investigated for their masking effect against caffeine. The most active compounds of the newly investigated taste modifiers were phloretin, the related dihydrochalcones 3-methoxy-2′,4,4′-trihydroxydihydrochalcone and 2′,4-dihydroxy-3-methoxydihydrochalcone, and the deoxybenzoin 2-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)ethanone. Starting with the whole set of compounds showing activity &gt;22%, a (Q)SAR pharmacophore model for maskers of caffeine bitterness was calculated to explain the structural requirements. After docking of the pharmacophore into a structural model of the broadly tuned bitter receptor hTAS2R10 and docking of enterolactone and enterodiol as only very weakly related structures, it was possible to predict qualitatively their modulating activity. Enterodiol (25 mg L–1) reduced the bitterness of the 500 mg L–1 caffeine solution by about 30%, whereas enterolactone showed no masking but a slight bitter-enhancing effect.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1417
TI  - Glutathione peroxidase-2 and selenium decreased inflammation and tumors in a mouse model of inflammation-associated carcinogenesis whereas sulforaphane effects differed with selenium supply
JO  - Carcinogenesis
PY  - 2012
SP  - 620-628
AU  - Krehl, S.
AU  - Loewinger, M.
AU  - Florian, S.
AU  - Kipp, A. P.
AU  - Banning, A.
AU  - Wessjohann, L. A.
AU  - Brauer, M. N.
AU  - Iori, R.
AU  - Esworthy, R. S.
AU  - Chu, F.-F.
AU  - Brigelius-Flohé, R.
AU  - 
VL  - 33
UR  - 
DO  - 10.1093/carcin/bgr288
AB  - Chronic inflammation and selenium deficiency are considered as risk factors for colon cancer. The protective effect of selenium might be mediated by specific selenoproteins, such as glutathione peroxidases (GPx). GPx-1 and -2 double knockout, but not single knockout mice, spontaneously develop ileocolitis and intestinal cancer. Since GPx2 is induced by the chemopreventive sulforaphane (SFN) via the nuclear factor E2-related factor 2 (Nrf2)/Keap1 system, the susceptibility of GPx2-KO and wild-type (WT) mice to azoxymethane and dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis was tested under different selenium states and SFN applications. WT and GPx2-KO mice were grown on a selenium-poor, -adequate or -supranutritional diet. SFN application started either 1 week before (SFN4) or along with (SFN3) a single AOM application followed by DSS treatment for 1 week. Mice were assessed 3 weeks after AOM for colitis and Nrf2 target gene expression and after 12 weeks for tumorigenesis. NAD(P)H:quinone oxidoreductases, thioredoxin reductases and glutathione-S-transferases were upregulated in the ileum and/or colon by SFN, as was GPx2 in WT mice. Inflammation scores were more severe in GPx2-KO mice and highest in selenium-poor groups. Inflammation was enhanced by SFN4 in both genotypes under selenium restriction but decreased in selenium adequacy. Total tumor numbers were higher in GPx2-KO mice but diminished by increasing selenium in both genotypes. SFN3 reduced inflammation and tumor multiplicity in both Se-adequate genotypes. Tumor size was smaller in Se-poor GPx2-KO mice. It is concluded that GPx2, although supporting tumor growth, inhibits inflammation-mediated tumorigenesis, but the protective effect of selenium does not strictly depend on GPx2 expression. Similarly, SFN requires selenium but not GPx2 for being protective.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1416
TI  - Synthesis and characterization of diacetyl platinum(II) complexes with two primary and secondary amine ligands
JO  - J. Organomet. Chem.
PY  - 2012
SP  - 93-101
AU  - Kluge, T.
AU  - Bette, M.
AU  - Vetter, C.
AU  - Schmidt, J.
AU  - Steinborn, D.
AU  - 
VL  - 715
UR  - 
DO  - 10.1016/j.jorganchem.2012.05.043
AB  - [Pt(COMe)2(bpy)] (2; bpy = 2,2′-bipyridine) and [Pt(COMe)2{H(Me)dmg}] (5; H(Me)dmg = MeO–NC(Me)–C(Me)N–OH) were found to react with primary and secondary amines yielding diacetyl platinum(II) complexes with two monodendate amine ligands [Pt(COMe)2(NH2R)2] (R = Bn, 3a; CH2CH2Ph, 3b; Et, 3c; i-Pr, 3d; CH2CHCH2, 3e; Cy, 3f; Bn = benzyl, Cy = cyclohexyl) and [Pt(COMe)2(NHR2)2] (R = Me, 6a; Et, 6b), respectively. The equilibrium of these ligand exchange reactions was investigated by NMR experiments and DFT calculations showing that complex 5 is the more preferable starting complex and a large excess of the amine has to be used. The sterically demanding diisopropylamine was found to react with 5 yielding a thermally highly unstable dinuclear bis(acetyl) bridged complex [{Pt(COMe){NH(i-Pr)2}}2(μ-COMe)2] (7). Analogous reactions with ethylenediamine derivatives resulted in the formation of [Pt(COMe)2(N^N)] (N^N = ethylenediamine, en, 8a; N,N′-dimethylethylenediamine, 8b; N,N-dimethylethylenediamine, 8c; N,N,N′,N′-tetramethylethylenediamine, TMEDA, 8d). All complexes were fully characterized by microanalysis/high-resolution ESI mass spectrometry, by NMR (1H, 13C, 195Pt) and IR spectroscopies as well as by single-crystal X-ray diffraction measurements (3a/3d). Due to the high trans influence of the acetyl ligands, the Pt–N bonds were found to be relatively long (2.164(2)–2.182(3) Å). The resulting weak coordination of the amines gave rise to a decomposition of complexes 3 under CO extrusion yielding carbonyl–methyl complexes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1414
TI  - Cytotoxic and antimicrobial constituents from the roots of Stemona cochinchinesis in Laos
JO  - Vietnam J. Chem.
PY  - 2012
SP  - 203-206
AU  - Khamko, V. A.
AU  - Dien, P. H.
AU  - Schmidt, J.
AU  - Quang, D. N.
AU  - 
VL  - 50
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1413
TI  - Improved synthesis of the chrysomelid pheromone (6R,7S)-(+)-himachala-9,11-diene via spontaneous bromination and didehydrobromination of 2,6,6,9-tetramethyl-bicyclo[5.4.0]undec-8-ene
JO  - ARKIVOC
PY  - 2012
SP  - 371-378
AU  - Jimenez-Aleman, G. H.
AU  - Schöner, T.
AU  - Montero-Alejo, A. L.
AU  - Brandt, W.
AU  - Boland, W.
AU  - 
VL  - 2012
UR  - 
DO  - 10.3998/ark.5550190.0013.326
AB  - A convenient synthesis of (6R,7S)-(+)-himachala-9,11-diene, the pheromone of the chrysomelid beetle Phyllotreta striolata is described. The diene is obtained in a single operation by a spontaneous “bromination/dehydrobromination” of 2,6,6,9-tetramethylbicyclo[5.4.0]undec-8-ene. The halogenation/dehalogenation sequence proceeds spontaneously in CCl4, and is less uniform in CH2Cl2 and CHCl3. 1H NMR experiments carried out in presence of the radical scavenger di-tert-butyl-4-methylphenol suggest an ionic mechanism for this reaction. Theoretical calculations demonstrate that the spontaneous reaction profits from the strongly exergonic addition of Br2 to the double bond and an almost neutral energy difference between the starting olefin and the diene pheromone.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1411
TI  - Virtual screening for plant PARP inhibitors – what can be learned from human PARP inhibitors?
JO  - J. Cheminform.
PY  - 2012
SP  - O24
AU  - Heym, P.-P.
AU  - Brandt, W.
AU  - Wessjohann, L. A.
AU  - Niclas, H.-J.
AU  - 
VL  - 4
UR  - 
DO  - 10.1186/1758-2946-4-S1-O24
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1409
TI  - Analysis of furanocoumarins from Yemenite Dorstenia species by liquid chromatography/electrospray tandem mass spectrometry
JO  - J. Mass Spectrom.
PY  - 2012
SP  - 7-22
AU  - Heinke, R.
AU  - Franke, K.
AU  - Michels, K.
AU  - Wessjohann, L.
AU  - Ali, N. A. A.
AU  - Schmidt, J.
AU  - 
VL  - 47
UR  - 
DO  - 10.1002/jms.2017
AB  - A series of prevailing prenylated furanocoumarins from leaves of Dorstenia gigas and Dorstenia foetida (Moraceae) were investigated by liquid chromatography/electrospray tandem mass spectrometry. The mass spectral behavior of the furanocoumarins under positive ion electrospray conditions is discussed using both an ion trap and a triple quadrupole system. It is demonstrated that both methods represent valuable tools not only for the rapid classification of this type of compounds, but also with respect to their substitution pattern.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1405
TI  - Flavonoid production in transgenic hop (Humulus lupulus L.) altered by PAP1/MYB75 from Arabidopsis thaliana L.
JO  - Plant Cell Rep.
PY  - 2012
SP  - 111-119
AU  - Gatica-Arias, A.
AU  - Farag, M. A.
AU  - Stanke, M.
AU  - Matoušek, J.
AU  - Wessjohann, L.
AU  - Weber, G.
AU  - 
VL  - 31
UR  - 
DO  - 10.1007/s00299-011-1144-5
AB  - Hop is an important source of secondary metabolites, such as flavonoids. Some of these are pharmacologically active. Nevertheless, the concentration of some classes as flavonoids in wild-type plants is rather low. To enhance the production in hop, it would be interesting to modify the regulation of genes in the flavonoid biosynthetic pathway. For this purpose, the regulatory factor PAP1/AtMYB75 from Arabidopsis thaliana L. was introduced into hop plants cv. Tettnanger by Agrobacterium-mediated genetic transformation. Twenty kanamycin-resistant transgenic plants were obtained. It was shown that PAP1/AtMYB75 was stably incorporated and expressed in the hop genome. In comparison to the wild-type plants, the color of female flowers and cones of transgenic plants was reddish to pink. Chemical analysis revealed higher levels of anthocyanins, rutin, isoquercitin, kaempferol-glucoside, kaempferol-glucoside-malonate, desmethylxanthohumol, xanthohumol, α-acids and β-acids in transgenic plants compared to wild-type plants.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1435
TI  - Carbohydrate–steroid conjugation by Ugi reaction: one-pot synthesis of triple sugar/pseudo-peptide/spirostane hybrids
JO  - Carbohyd. Res.
PY  - 2012
SP  - 102-110
AU  - Rivera, D. G.
AU  - Pérez-Labrada, K.
AU  - Lambert, L.
AU  - Dörner, S.
AU  - Westermann, B.
AU  - Wessjohann, L. A.
AU  - 
VL  - 359
UR  - 
DO  - 10.1016/j.carres.2012.05.003
AB  - The one-pot synthesis of novel molecular chimeras incorporating sugar, pseudo-peptide, and steroidal moieties is described. For this, a new carbohydrate–steroid conjugation approach based on the Ugi four-component reaction was implemented for the ligation of glucose and chacotriose to spirostanic steroids. The approach proved wide substrate scope, as both mono and oligosaccharides functionalized with amino, carboxy, and isocyano groups were conjugated to steroidal substrates in an efficient, multicomponent manner. Two alternative strategies based on the hydrazoic acid variant of the Ugi reaction were employed for the synthesis of tetrazole-based chacotriose–diosgenin conjugates resembling naturally occurring spirostan saponins. This is the first time that triple sugar/pseudo-peptide/steroid hybrids are produced, thus opening up an avenue of opportunities for applications in drug discovery and biological chemistry.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 91
TI  - Multiple Multicomponent Reactions with Isocyanides
T2  - Isocyanide Chemistry: Applications in Synthesis and Material Science
PB  - 
PY  - 2012
SP  - 233-262
AU  - Wessjohann, L. A.
AU  - Neves Filho, R. A. W.
AU  - Rivera, D. G.
AU  - 
VL  - 
UR  - 
SN  - 9783527652532
DO  - 10.1002/9783527652532.ch7
AB  - This chapter contains sections titled:IntroductionOne‐Pot Multiple IMCRsIsocyanide‐Based Multiple Multicomponent MacrocyclizationsSequential Isocyanide‐Based MCRsConclusionsReferences
A2  - Nenajdenko, V. G., ed.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 90
TI  - Control of Plastidial Isoprenoid Precursor Supply: Divergent 1-Deoxy-D-Xylulose 5-Phosphate Synthase (DXS) Isogenes Regulate the Allocation to Primary or Secondary Metabolism
T2  - Isoprenoid Synthesis in Plants and Microorganisms
PB  - 
PY  - 2012
SP  - 251-270
AU  - Walter, M. H.
AU  - Floss, D. S.
AU  - Paetzold, H.
AU  - Manke, K.
AU  - Vollrath, J.
AU  - Brandt, W.
AU  - Strack, D.
AU  - 
VL  - 
UR  - 
SN  - 978-1-4614-4063-5
DO  - 10.1007/978-1-4614-4063-5_17
AB  - Following the description of two separate pathways for isoprenoid precursor biosynthesis in plants, a new level of complexity has been introduced by the discovery of two divergent gene classes encoding the first enzyme of the plastidial methylerythritol phosphate (MEP) pathway. These nonredundant 1-deoxy-d-xylulose 5-phosphate synthase (DXS) isogenes are differentially expressed in such a way that DXS1 appears to serve housekeeping functions, whereas DXS2 is associated with the production of specialized (secondary) isoprenoids involved in ecological functions. Examples of the latter are apocarotenoid formation in roots colonized by arbuscular mycorrhizal fungi and mono- or diterpenoid biosynthesis in trichomes. Knockdown of DXS2 genes can specifically suppress secondary isoprenoid formation without affecting basic plant functions. Analyzing DXS isogenes along the progression of land plant evolution shows separation in structure and complementary expression already at the level of gymnosperms, which is maintained in all angiosperms except Arabidopsis.
A2  - Bach, T. J. &amp; Rohmer, M., eds.
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1501
TI  - Discrimination between the regioisomeric 1,2- and 1,3-diacylglycerophosphocholines by phospholipases
JO  - Chem. Phys. Lipids
PY  - 2011
SP  - 196-204
AU  - Mansfeld, J.
AU  - Brandt, W.
AU  - Haftendorn, R.
AU  - Schöps, R.
AU  - Ulbrich-Hofmann, R.
AU  - 
VL  - 164
UR  - 
DO  - 10.1016/j.chemphyslip.2010.12.009
AB  - The artificial 1,3-diacyl-glycero-2-phosphocholines (1,3-PCs), which form similar aggregate structures as the naturally occurring 1,2-diacyl-sn-glycero-3-phosphocholines (1,2-PCs), were tested as substrates for different classes of phospholipases such as phospholipase A2 (PLA2) from porcine pancreas, bee and snake venom, and Arabidopsis thaliana, phospholipase C (PLC) from Bacillus cereus, and phospholipase D (PLD) from cabbage and Streptomyces species. The regioisomers of the natural phospholipids were shown to bind to all investigated phospholipases with an affinity similar to the corresponding naturally occurring phospholipids, however their hydrolysis was reduced to different degrees (PLA2s and PLC) or even abolished (PLDs belonging to the PLD superfamily). The results are in accordance with binding models obtained by docking the substrates to the crystal structures or homology models of the phospholipases.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1500
TI  - Alkaloids from Papaver coreanum
JO  - Nat. Prod. Commun.
PY  - 2011
SP  - 1593-1594
AU  - Lee, D.-U.
AU  - Park, J. H.
AU  - Wessjohann, L.
AU  - Schmidt, J.
AU  - 
VL  - 6
UR  - 
DO  - 10.1177/1934578X1100601109
AB  - The alkaloid pattern of the endemic plant Papaver coreanum Nakai (Papaveraceae) was determined for the first time. Eight alkaloids could be identified by LC/ESIMS/MS and high-resolution mass spectrometry. Among them, protopine and allocryptopine represent the main components. Besides norsanguinarine, sanguinarine, dihydrosanguinarine, oxysanguinarine, lincangenine, and cryptopine, some other trace alkaloids were found whose structures remain unknown.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1499
TI  - Chemoenzymatic synthesis of diverse thiohydroximates from glucosinolate-utilizing enzymes from Helix pomatia and Caldicellulosiruptor saccharolyticus
JO  - Biotechnol. Lett.
PY  - 2011
SP  - 1039-1046
AU  - Kopycki, J.
AU  - Schmidt, J.
AU  - Abel, S.
AU  - Grubb, C. D.
AU  - 
VL  - 33
UR  - 
DO  - 10.1007/s10529-011-0530-y
AB  - Thiohydroximates comprise a diverse class of compounds important in both biological and industrial chemistry. Their syntheses are generally limited to simple alkyl and aryl compounds with few stereocenters and a narrow range of functional groups. We hypothesized that sequential action of two recombinant enzymes, a sulfatase from Helix pomatia and a β-O-glucosidase from Caldicellulosiruptor saccharolyticus, on glucosinolates would allow synthesis of thiohydroximates from a structurally broad array of abundant precursors. We report successful synthesis of thiohydroximates of varied chemical classes, including from homochiral compounds of demonstrated biological activity. The chemoenzymatic synthetic route reported here should allow access to many, if not all, of the thiohydroximate core structures of the ~200 known naturally occurring glucosinolates. The enrichment of this group for compounds with possible pharmacological potential is discussed.
A2  - 
C1  - Molecular Signal Processing; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1491
TI  - Furanocoumarins from Dorstenia foetida
JO  - Phytochemistry
PY  - 2011
SP  - 929-934
AU  - Heinke, R.
AU  - Franke, K.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - Awadh Ali, N. A.
AU  - Schmidt, J.
AU  - 
VL  - 72
UR  - 
DO  - 10.1016/j.phytochem.2011.03.008
AB  - The linear furanocoumarins 5-(2,3-epoxy-3-methyl-butoxy)-chalepensin, 5-methoxy-3-(3-methyl-2,3-dihydroxybutyl)-psoralen-diacetate (7), 5-methoxy-3-[3-(β-d-glucopyranosyloxy)-2-acetyloxy-3-methyl-butyl]-psoralen and 5-(3-methyl-2,3-dihydroxybutyloxy)-3-[3-(β-d-glucopyranosyloxy)-2-hydroxy-3-methyl-butyl]-psoralen, and the coumarin derivative 7-hydroxy-5-methoxy-6-carboxymethyl-3-[3-(β-d-glucopyranosyloxy)-2-hydroxy-3-methyl-butyl]-coumarin were isolated from the leaves of Dorstenia foetida (Moraceae) along with the known compounds psoralen, bergapten, isopimpinellin, phellopterin, 5-methoxychalepensin and turbinatocoumarin. Further furanocoumarins were characterized by ESI-MS/MS investigations. The nonpolar extracts of D. foetida exhibit antifungal, antibacterial and cytotoxic activity, however, no anthelminthic activity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1486
TI  - A Whole-Plant Microtiter Plate Assay for Drought Stress Tolerance-Inducing Effects
JO  - J. Plant Growth Regul.
PY  - 2011
SP  - 504-511
AU  - Geissler, T.
AU  - Wessjohann, L. A.
AU  - 
VL  - 30
UR  - 
DO  - 10.1007/s00344-011-9212-1
AB  - The frequency and intensity of extreme weather events and global temperature are rising, which poses a potential threat to life, specifically crops, and therefore food and bioenergy supply. Reduced water availability has the most severe impact on potential grain yield. Negative effects of transient drought stress (dry spells) can be countered by drought tolerance-inducing chemicals. In search for useful compounds, biochemical assays are fast but limited in scope, whereas whole-plant assays are slow, require large amounts of compounds, and are usually not concentration-related. Here we report the development of a fast, concentration-dependent whole-plant assay using the fast growing duckweed Lemna minor L. 4-Amino-1,8-naphthalimide (1) and the imidacloprid metabolite 6-chloronicotinic acid (2) were affirmed as drought stress tolerance enhancers. Both also reduce oxidative stress-induced cell death in Arabidopsis thaliana (L.) Heynh. cell suspension culture but show differences in their mode of action.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1485
TI  - The Bladder Tumor Suppressor Protein TERE1 (UBIAD1) Modulates Cell Cholesterol: Implications for Tumor Progression
JO  - DNA Cell Biol.
PY  - 2011
SP  - 851-864
AU  - Fredericks, W. J.
AU  - McGarvey, T.
AU  - Wang, H.
AU  - Lal, P.
AU  - Puthiyaveettil, R.
AU  - Tomaszewski, J.
AU  - Sepulveda, J.
AU  - Labelle, E.
AU  - Weiss, J. S.
AU  - Nickerson, M. L.
AU  - Kruth, H. S.
AU  - Brandt, W.
AU  - Wessjohann, L. A.
AU  - Malkowicz, S. B.
AU  - 
VL  - 30
UR  - 
DO  - 10.1089/dna.2011.1315
AB  - Convergent evidence implicates the TERE1 protein in human bladder tumor progression and lipid metabolism. Previously, reduced TERE1 expression was found in invasive urologic cancers and inhibited cell growth upon re-expression. A role in lipid metabolism was suggested by TERE1 binding to APOE, a cholesterol carrier, and to TBL2, a candidate protein in triglyceride disorders. Natural TERE1 mutations associate with Schnyder&#39;s corneal dystrophy, characterized by lipid accumulation. TERE1 catalyzes menaquinone synthesis, known to affect cholesterol homeostasis. To explore this relationship, we altered TERE1 and TBL2 dosage via ectopic expression and interfering RNA and measured cholesterol by Amplex red. Protein interactions of wild-type and mutant TERE1 with GST-APOE were evaluated by binding assays and molecular modeling. We conducted a bladder tumor microarray TERE1 expression analysis and assayed tumorigenicity of J82 cells ectopically expressing TERE1. TERE1 expression was reduced in a third of invasive specimens. Ectopic TERE1 expression in J82 bladder cancer cells dramatically inhibited nude mouse tumorigenesis. TERE1 and TBL2 proteins inversely modulated cellular cholesterol in HEK293 and bladder cancer cells from 20% to 50%. TERE1 point mutations affected APOE interactions, and resulted in cholesterol levels that differed from wild type. Elevated tumor cell cholesterol is known to affect apoptosis and growth signaling; thus, loss of TERE1 in invasive bladder cancer may represent a defect in menaquinone-mediated cholesterol homeostasis that contributes to progression.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1482
TI  - Oxidative allylic rearrangement of cycloalkenols: Formal total synthesis of enantiomerically pure trisporic acid B
JO  - Beilstein J. Org. Chem.
PY  - 2011
SP  - 421-425
AU  - Dubberke, S.
AU  - Abbas, M.
AU  - Westermann, B.
AU  - 
VL  - 7
UR  - 
DO  - 10.3762/bjoc.7.54
AB  - Enantiomerically highly enriched unsaturated β-ketoesters bearing a quaternary stereocenter can be utilized as building blocks for the synthesis of natural occurring terpenes, i. a., trisporic acid and its derivatives. An advanced building block has been synthesized in a short reaction sequence, which involves an oxidative allylic rearrangement initiated by pyridinium dichromate (PDC) as the key step.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1479
TI  - Isomerization of the Phytohormone Precursor 12-Oxophytodienoic Acid (OPDA) in the Insect Gut
JO  - J. Biol. Chem.
PY  - 2011
SP  - 22348-22354
AU  - Dąbrowska, P.
AU  - Shabab, M.
AU  - Brandt, W.
AU  - Vogel, H.
AU  - Boland, W.
AU  - 
VL  - 286
UR  - 
DO  - 10.1074/jbc.M111.244509
AB  - 12-Oxophytodienoic acid (OPDA) is isomerized in the gut of herbivorous insects to tetrahydrodicranenone B (iso-OPDA). The transformation is achieved by a glutathione S-transferase present in the gut epithelium. Experiments with 9-[2H]-iso-OPDA demonstrated the complete retention of the deuterium atom in the product 11-[2H]-OPDA consistent with an intramolecular 1,3-hydrogen shift. Homology modeling based on the x-ray structure of a glutathione S-transferase from Anopheles gambiae revealed that the co-factor glutathione does not covalently bind to the substrate but appears to be involved in the initial deprotonation and enolization of the OPDA. The transformation resembles that of a mammalian GST-catalyzed isomerization of Δ5-3-ketosteroids to Δ4-3-ketosteroids or the conversion of prostaglandin A1 to the biologically inactive prostaglandin B1.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1475
TI  - Systematic conformational investigations of peptoids and peptoid-peptide chimeras
JO  - Biopolymers
PY  - 2011
SP  - 651-668
AU  - Brandt, W.
AU  - Herberg, T.
AU  - Wessjohann, L.
AU  - 
VL  - 96
UR  - 
DO  - 10.1002/bip.21620
AB  - Peptoids are originally defined as N‐substituted oligoglycine derivatives, and in a broader definition as N‐substituted peptides (peptoid–peptide chimeras). Both types were systematically investigated by force field calculations. The Merck MMFF and YASARA2 force fields were shown to be, among others, the most suitable ones for conformational investigations of peptoids with no missing parameterizations, in contrast to AMBER or CHARMM. Ramachandran‐like plots were calculated for dipeptoids and chimeras using energy calculations and grid searches by varying the dihedral angels Φ and Ψ in steps of 10° for s‐cis‐ and s‐trans amide bonds. Barriers as well as low energy conformations are compared to peptide Ramachandran plots, showing that peptoids have both, more barriers due to additional steric interactions as well as access to minimum conformations not accessible by peptides. Low energy conformations of dimers were used as starting conformations of higher oligomers of the peptoids for extensive molecular dynamics simulations over 10 or 20 ns with the YASARA2 force field and an explicit water solvent box to evaluate their potential to form secondary structural elements. Especially peptoids with aminoisobutyric acid‐like monomer units were found to form left‐handed or polyproline‐like helices also known from less common natural peptides. Furthermore, new secondary structures appear feasible based on stable conformations outside the allowed areas of the Ramachandran plot for peptides, but allowed for peptoids.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1474
TI  - Rhodium(I) complexes with κP coordinated ω-phosphinofunctionalized alkyl phenyl sulfide, sulfoxide and sulfone ligands and their reactions with sodium bis(trimethylsilyl)amide and Ag[BF4]
JO  - J. Organomet. Chem.
PY  - 2011
SP  - 1768-1781
AU  - Block, M.
AU  - Bette, M.
AU  - Wagner, C.
AU  - Schmidt, J.
AU  - Steinborn, D.
AU  - 
VL  - 696
UR  - 
DO  - 10.1016/j.jorganchem.2010.12.019
AB  - Reactions of ω-diphenylphosphinofunctionalized alkyl phenyl sulfides Ph2P(CH2)nSPh (n = 1, 1a; 2, 2a; 3, 3a), sulfoxides Ph2P(CH2)nS(O)Ph (n = 1, 1b; 2, 2b; 3, 3b) and sulfones Ph2P(CH2)nS(O)2Ph (n = 1, 1c; 2, 2c; 3, 3c) with dinuclear chlorido bridged rhodium(I) complexes [(RhL2)2(μ-Cl)2] (L2 = cycloocta-1.5-diene, cod, 4; bis(diphenylphosphino)ethane, dppe, 5) afforded mononuclear Rh(I) complexes of the type [RhCl{Ph2P(CH2)nS(O)xPh-κP}(cod)]1 (n/x = 1/0, 6a; 1/1, 6b; 1/2, 6c; 2/0, 8a; 2/1, 8b; 2/2, 8c; 3/0, 10a; 3/1, 10b; 3/2, 10c) and [RhCl{Ph2P(CH2)nS(O)xPh-κP}(dppe)] (n/x = 1/0, 7a; 1/1, 7b; 1/2, 7c; 2/0, 9a; 2/1, 9b; 2/2, 9c; 3/0, 11a; 3/1, 11b; 3/2, 11c) having the P^S(O)x ligands κP coordinated. Addition of Ag[BF4] to complexes 6–11 in CH2Cl2 led with precipitation of AgCl to cationic rhodium complexes of the type [Rh{Ph2P(CH2)nS(O)xPh-κP,κS/O}L2][BF4] having bound the P^S(O)x ligands bidentately in a κP,κS (13a–18a, 15b–18b) or a κP,κO (13b, 14b, 13c–18c) coordination mode. Unexpectedly, the addition of Ag[BF4] to 6a in THF afforded the trinuclear cationic rhodium(I) complex [Rh3(μ-Cl)(μ-Ph2PCH2SPh-κP:κS)4][BF4]2·4THF (12·4THF) with a four-membered Rh3Cl ring as basic framework. Addition of sodium bis(trimethylsilyl)amide to complexes 6–11 led to a selective deprotonation of the carbon atom neighbored to the S(O)x group (α-C) yielding three different types of organorhodium complexes: a) Organorhodium intramolecular coordination compounds of the type [Rh{CH{S(O)xPh}CH2CH2PPh2-κC,κP}L2] (22a–c, 23a–c), b) zwitterionic complexes [Rh{Ph2PCHS(O)xPh-κP,κS/O}L2] having κP,κS (21a, 21b) and κP,κO (20b/c, 21c) coordinated anionic [Ph2PCHS(O)xPh] ligands, and c) the dinuclear rhodium(I) complex [{Rh{μ-CH(SPh)PPh2-κC:κP}(cod)}2] (19). All complexes were fully characterized spectroscopically and complexes 15b, 15c, 12·4THF and 19·THF additionally by X-ray diffraction analysis. DFT calculations of zwitterionic complexes gave insight into the coordination mode of the [Ph2PCHS(O)Ph] ligand (κP,κS versus κP,κO).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1472
TI  - Fast and efficient microwave-assisted synthesis of functionalized peptoids via Ugi reactions
JO  - Org. Biomol. Chem.
PY  - 2011
SP  - 5024-5027
AU  - Barreto, A. d. F. S.
AU  - Vercillo, O. E.
AU  - Birkett, M. A.
AU  - Caulfield, J. C.
AU  - Wessjohann, L. A.
AU  - Andrade, C. K. Z.
AU  - 
VL  - 9
UR  - 
DO  - 10.1039/C1OB05471F
AB  - A wide range of N-alkylglycines (peptoids) can be efficiently prepared viaUgi reactions using microwave irradiations. The results confirm the versatility and efficiency of the methodology for the preparation of functionalized peptoids. The products can be used in consecutive Ugi reactions to yield cyclic peptoids of potential biological interest.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1470
TI  - Anticholinesterase activity of endemic plant extracts from Soqotra
JO  - Afr. J. Tradit. Complement. Altern. Med.
PY  - 2011
SP  - 296-299
AU  - Bakthir, H.
AU  - Awadh Ali, N. A.
AU  - Arnold, N.
AU  - Teichert, A.
AU  - Wessjohann, L.
AU  - 
VL  - 8
UR  - 
DO  - 10.4314/ajtcam.v8i3.65292
AB  - A total of 30 chloroform and methanol extracts from the following endemic Soqotran plants Acridocarpus socotranus Olive, Boswellia socotranao Balf.fil, Boswellia elongata Balf. fil., Caralluma socotrana N. Br, Cephalocroton socotranus Balf.f, Croton socotranus Balf. fil.., Dendrosicycos socotrana Balf.f., Dorstenia gigas Schweinf. ex Balf. fil., Eureiandra balfourii Cogn. &amp; Balf. fil., Kalanchoe farinaceae Balf.f, Limonium sokotranum (Vierh) Radcl. Sm), Oldenlandia pulvinata, Pulicaria diversifolia( Balf. and Pulicaria stephanocarpa Balf. were screened for their acetylcholinesterase inhibitory activity by using in vitro Ellman method at 50 and 200 μg/ml concentrations. Chloroform extracts of Croton socotranus, Boswellia socotrana, Dorstenia gigas, and Pulicaria stephanocarpa as well as methanol extracts of Eureiandra balfourii exhibited inhibitory activities higher than 50 % at concentration of 200 μg. At a concentrations of 50 μg, the chloroform extract of Croton socotranus exhibited an inhibition of 40.6 %.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1528
TI  - Secondary metabolites from Helichrysum foetidum and their chemotaxonomic significance
JO  - Biochem. Syst. Ecol.
PY  - 2011
SP  - 166-167
AU  - Zanetsie Kakam, A. M.
AU  - Franke, K.
AU  - Ndom, J. C.
AU  - Dongo, E.
AU  - Mpondo, T. N.
AU  - Wessjohann, L. A.
AU  - 
VL  - 39
UR  - 
DO  - 10.1016/j.bse.2011.02.005
AB  - The occurrence of tetracyclic kauran type diterpenoids or related structures might be a valuable chemotaxonomic marker for further classification and subdivision of the polyphyletic genus Helichrysum.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1527
TI  - Compositional and Structural Studies of the Major and Minor Components in Three Cameroonian Seed Oils by GC–MS, ESI-FTICR-MS and HPLC
JO  - J. Am. Oil. Chem. Soc.
PY  - 2011
SP  - 1539-1549
AU  - Yeboah, S. O.
AU  - Mitei, Y. C.
AU  - Ngila, J. C.
AU  - Wessjohann, L.
AU  - Schmidt, J.
AU  - 
VL  - 88
UR  - 
DO  - 10.1007/s11746-011-1832-x
AB  - The lipid components of three Cameroonian seed oils, ke tchock (Aframomum arundinaceum), njangsa (Ricinodendron heudelotii) and calabash nutmeg (Monodora myristica), have been investigated. Gas chromatography (GC)–mass spectrometry (MS) fatty acid (FA) analysis showed M. myristica seed oil to be dominated by linoleic (49.29%) and oleic (37.17%) acids; R. heudelotii was mainly linoleic (58.73%), followed by stearic (15.00%) and oleic (14.21%) acids; A. arundinaceum was predominantly oleic (65.76%) and palmitic (20.36%) acids. Electrospray ionization (ESI)-Fourier transform ion cyclotron resonance (FTICR)-MS analysis showed seven major triacylglycerol (TAG) classes for M. myristica, with C54:5, C54:4 and C54:6 dominating. R. heudelotii had eight major TAG classes with C54:8, C54:7 and C54:6 being most abundant. A. arundinaceum also had eight major TAG classes with C52:2, C54:3 and C50:2 dominating. 13C nuclear magnetic resonance (NMR) analysis of the TAGs showed that both sn-1,3 and sn-2 positions were predominantly occupied by linoleoyl and oleoyl chains. High-performance liquid chromatography (HPLC) fluorescence detector (FLD) analysis showed that M. myristica contained only α- and β-tocopherols (195.40 and 73.95 µg/g, respectively), R. heudelotii contained mainly γ-tocopherol (289.40 µg/g), and A. arundinaceum had mainly γ- and β-tocopherols (236.78 and 124.93 µg/g, respectively). GC–MS analysis of the unsaponifiable matter showed that β-sitosterol was the most abundant phytosterol in all three seed oils. The absolute amounts of 4-desmethylsterols were 196.15, 608.71 and 362.15 µg/g for M. myristica, R. heudelotii and A. arundinaceum seed oils, respectively. These compositional and structural studies provide justification for the use of all three seed oils in food products.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1524
TI  - PdII/IV catalyzed oxidative cyclization of 1,6-enynes derived by Ugi-4-component reaction
JO  - Tetrahedron Lett.
PY  - 2011
SP  - 6295-6297
AU  - Welsch, S. J.
AU  - Umkehrer, M.
AU  - Ross, G.
AU  - Kolb, J.
AU  - Burdack, C.
AU  - Wessjohann, L. A.
AU  - 
VL  - 52
UR  - 
DO  - 10.1016/j.tetlet.2011.09.094
AB  - A variety of 1,6-enynes were synthesized by an Ugi-reaction and further elaborated by a PdII/IV catalyzed oxidative cyclization to produce N-substituted 3-aza-bicyclo[3.1.0]hexan-2-ones. Different substitution patterns were tested to examine the scope and limitations of the amide tethered substrates.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1518
TI  - Isolation of a New Natural Product and Cytotoxic and Antimicrobial Activities of Extracts from Fungi of Indonesian Marine Habitats
JO  - Mar. Drugs
PY  - 2011
SP  - 294-306
AU  - Tarman, K.
AU  - Lindequist, U.
AU  - Wende, K.
AU  - Porzel, A.
AU  - Arnold, N.
AU  - Wessjohann, L. A.
AU  - 
VL  - 9
UR  - 
DO  - 10.3390/md9030294
AB  - In the search for bioactive compounds, 11 fungal strains were isolated from Indonesian marine habitats. Ethyl acetate extracts of their culture broth were tested for cytotoxic activity against a urinary bladder carcinoma cell line and for antifungal and antibacterial activities against fish and human pathogenic bacteria as well as against plant and human pathogenic fungi. The crude extract of a sterile algicolous fungus (KT31), isolated from the red seaweed Kappaphycus alvarezii (Doty) Doty ex P.C. Silva exhibited potent cytotoxic activity with an IC50 value of 1.5 µg/mL. Another fungal strain (KT29) displayed fungicidal properties against the plant pathogenic fungus Cladosporium cucumerinum Ell. et Arth. at 50 µg/spot. 2-Carboxy-8-methoxy-naphthalene-1-ol (1) could be isolated as a new natural product.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1516
TI  - Interactions of polysulfanes with components of red blood cells
JO  - Med. Chem. Commun.
PY  - 2011
SP  - 196-200
AU  - Schneider, T.
AU  - Ba, L. A.
AU  - Khairan, K.
AU  - Zwergel, C.
AU  - Bach, N. D.
AU  - Bernhardt, I.
AU  - Brandt, W.
AU  - Wessjohann, L.
AU  - Diederich, M.
AU  - Jacob, C.
AU  - 
VL  - 2
UR  - 
DO  - 10.1039/C0MD00203H
AB  - Traditionally, the activity of most polysulfanes has been associated with the redox behaviour of the sulfur-sulfur bond. Here we show that polysulfanes, such as diallyltri- and tetrasulfide, also interact with cellular membranes and certain metalloproteins. Together, multiple interactions with various biological targets may explain best the biological activity of such compounds.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1512
TI  - Antibacterial and antioxidant activities and acute toxicity of Bumelia sartorum Mart., Sapotaceae, a Brazilian medicinal plant
JO  - Rev. Bras. Farmacogn.
PY  - 2011
SP  - 86-91
AU  - Ruela, H. S.
AU  - Leal, I. C. R.
AU  - de Almeida, M. R. A.
AU  - dos Santos, K. R. N.
AU  - Wessjohann, L. A.
AU  - Kuster, R. M.
AU  - 
VL  - 21
UR  - 
DO  - 10.1590/S0102-695X2011005000035
AB  - In order to validate the Bumelia sartorum Mart., Sapotaceae, traditional use for infection diseases, this study evaluates the antibacterial activity of the stem bark fractions against methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus strains by using the agar dilution method and reported as MIC (minimal inhibitory concentration). In addition, the DPPH scavenging activity of these fractions was measured and the chemical composition and acute toxicity of the active fraction were also determined. The ethyl acetate (EtOAc) extract was chemically analyzed by LC/MS, direct ionization APCI/MS, 1H NMR and 13C-NMR. All fractions, except butanol extract, presented high antioxidant activity, especially the methanol and the EtOAc extracts, which showed EC50 values (5.67 and 5.30 µg/mL, respectively) considerably lower than the Gingko-standard EGb 761® (38.58 µg/mL). The antibacterial activity against S. aureus strains was observed in EtOAc (MIC 256-512 µg/mL), which showed a very low toxicity. The chemical study of this fraction revealed the abundant presence of polyphenolic compounds. The antibacterial and antioxidant activities reported in this paper for EtOAc extract from B. sartorum and the low toxicity of this fraction opens the possibility that it could be helpful for the developing of new antibacterial agents for treating S. aureus infections.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1511
TI  - Topical anti-inflammatory activity of quillaic acid from Quillaja saponaria Mol. and some derivatives
JO  - J. Pharm. Pharmacol.
PY  - 2011
SP  - 718-724
AU  - Rodríguez-Díaz, M.
AU  - Delporte, C.
AU  - Cartagena, C.
AU  - Cassels, B. K.
AU  - González, P.
AU  - Silva, X.
AU  - León, F.
AU  - Wessjohann, L. A.
AU  - 
VL  - 63
UR  - 
DO  - 10.1111/j.2042-7158.2011.01263.x
AB  - Objectives  Quillaic acid is the major aglycone of the widely studied saponins of the Chilean indigenous tree Quillaja saponaria Mol. The industrial availability of quillaja saponins and the extensive functionalisation of this triterpenoid provide unique opportunities for structural modification and pose a challenge from the standpoint of selectivity in regard to one or the other secondary alcohol group, the aldehyde, and the carboxylic acid functions. The anti‐inflammatory activity of this sapogenin has not been studied previously and it has never been used to obtain potential anti‐inflammatory derivatives.Methods  A series of quillaic acid derivatives were prepared and subjected to topical assays for the inhibition of inflammation induced by arachidonic acid or phorbol ester.Key findings  Quillaic acid exhibited strong topical anti‐inflammatory activity in both models. Most of its derivatives were less potent, but the hydrazone 8 showed similar potency to quillaic acid in the TPA assay.Conclusions  The structural modifications performed and the biological results suggest that the aldehyde and carboxyl groups are relevant to the anti‐inflammatory activity in these models.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1510
TI  - Characterization of the anticancer properties of monoglycosidic cardenolides isolated from Nerium oleander and Streptocaulon tomentosum
JO  - J. Ethnopharmacol.
PY  - 2011
SP  - 781-788
AU  - Rashan, L. J.
AU  - Franke, K.
AU  - Khine, M. M.
AU  - Kelter, G.
AU  - Fiebig, H. H.
AU  - Neumann, J.
AU  - Wessjohann, L. A.
AU  - 
VL  - 134
UR  - 
DO  - 10.1016/j.jep.2011.01.038
AB  - Aim of the studyFor identification of the active constituents we investigated the anticancer activity of cardenolides from Streptocaulon tomentosum Wight &amp; Arn. (Asclepiadaceae) and from Nerium oleander L. (Apocynaceae) which are both used against cancer in the traditional medicine in their region of origin.Material, methods and resultsThe antiproliferative activity of cardenolides isolated from roots of Streptocaulon tomentosum (IC50 &lt; 1–15.3 μM after 2 days in MCF7) and of cardenolide containing fractions from the cold aqueous extract of Nerium oleander leaves (“Breastin”, mean IC50 0.85 μg/ml in a panel of 36 human tumor cell lines), their influence on the cellular viability and on the cell cycle (block at the G2/M-phase or at the S-phase in tumor cells, respectively) were determined using different cell lines. The murine cell line L929 and normal non-tumor cells were not affected. Bioactivity guided fractionation of Breastin resulted in the isolation of the monoglycosidic cardenolides oleandrine, oleandrigeninsarmentoside, neritaloside, odoroside H, and odoroside A (IC50-values between 0.010 and 0.071 μg/ml).ConclusionsThe observed anticancer activities of extracts and isolated cardenolides are in agreement with the ethnomedicinal use of Streptocaulon tomentosum and Nerium oleander. The most active anticancer compounds from both species are monoglycosidic cardenolides possessing the 3β,14β-dihydroxy-5β-card-20(22)-enolide structure with or without an acetoxy group at C-16. The results indicate that the cytotoxic effects are induced by the inhibition of the plasma membrane bound Na+/K+-ATPase.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1507
TI  - The Multiple Multicomponent Approach to Natural Product Mimics: Tubugis, N-Substituted Anticancer Peptides with Picomolar Activity
JO  - J. Am. Chem. Soc.
PY  - 2011
SP  - 7692-7695
AU  - Pando, O.
AU  - Stark, S.
AU  - Denkert, A.
AU  - Porzel, A.
AU  - Preusentanz, R.
AU  - Wessjohann, L. A.
AU  - 
VL  - 133
UR  - 
DO  - 10.1021/ja2022027
AB  - The synthesis of a new generation of highly cytotoxic tubulysin analogues (i.e., tubugis) is described. In the key step, the rare, unstable, and synthetically difficult to introduce tertiary amide–N,O-acetal moiety required for high potency in natural tubulysins is replaced by a dipeptoid element formed in an Ugi four-component reaction. Two of the four components required are themselves produced by other multicomponent reactions (MCRs). Thus, the tubugis represent the first examples of the synthesis of natural-product-inspired compounds using three intertwined isonitrile MCRs.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1506
TI  - Synthesis of (−)-julocrotine and a diversity oriented Ugi-approach to analogues and probes
JO  - Beilstein J. Org. Chem.
PY  - 2011
SP  - 1504-1507
AU  - Neves Filho, R. A. W.
AU  - Westermann, B.
AU  - Wessjohann, L. A.
AU  - 
VL  - 7
UR  - 
DO  - 10.3762/bjoc.7.175
AB  - An improved total synthesis of (−)-julocrotine in three steps from Cbz-glutamine, in 51% overall yield, is presented. To demonstrate the potential of the heterocyclic moiety for diversity oriented synthesis, a series of (−)-julocrotine analogues was synthesized by employing the heterocyclic precursor as an amino input in Ugi four-component reactions (Ugi-4CR) [1].
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1505
TI  - Cation–π and π–π stacking interactions allow selective inhibition of butyrylcholinesterase by modified quinine and cinchonidine alkaloids
JO  - Biochem. Biophys. Res. Commun.
PY  - 2011
SP  - 935-940
AU  - Nawaz, S. A.
AU  - Ayaz, M.
AU  - Brandt, W.
AU  - Wessjohann, L. A.
AU  - Westermann, B.
AU  - 
VL  - 404
UR  - 
DO  - 10.1016/j.bbrc.2010.12.084
AB  - Scaffold varied quaternized quinine and cinchonidine alkaloid derivatives were evaluated for their selective butyrylcholinesterase (BChE) inhibitory potential. Ki values were between 0.4–260.5 μM (non-competitive inhibition) while corresponding Kivalues to acetylcholinesterase (AChE) ranged from 7.0–400 μM exhibiting a 250-fold selectivity for BChE.Docking arrangements (GOLD, PLANT) revealed that the extended aromatic moieties and the quaternized nitrogen of the inhibitors were responsible for specific π–π stacking and π–cation interactions with the choline binding site and the peripheral anionic site of BChE’s active site.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 99
TI  - Multi-Component Reactions in Supramolecular Chemistry and Material Science
T2  - MCR 2009
PB  - Adv. Exp. Med. Biol.
PY  - 2011
SP  - 173-201
AU  - Wessjohann, L. A.
AU  - Ostrowski, S.
AU  - Bakulev, V.
AU  - Berseneva, V.
AU  - Bogdanov, A. V.
AU  - Romanova, I. P.
AU  - Mironov, V. F.
AU  - Larionova, O. A.
AU  - Shaikhutdinova, G. R.
AU  - Sinyashin, O. G.
AU  - Baibulatova, N. Z.
AU  - Dokichev, V. A.
AU  - Fedorova, O. V.
AU  - Ovchinnikova, I. G.
AU  - Rusinov, G. L.
AU  - Titova, J. A.
AU  - Nasonova, A.
AU  - Kim, D.-J.
AU  - Kim, K.-S.
AU  - Jang, Y. M.
AU  - Kim, S. J.
AU  - Rakhimova, E. B.
AU  - Minnebaev, A. B.
AU  - Akhmetova, V. R.
AU  - Qin, C.
AU  - Zhang, R.
AU  - Wang, Q.
AU  - Ren, J.
AU  - Tian, L.
AU  - Mironov, M. A.
AU  - Demina, T. S.
AU  - Tcoy, A. M.
AU  - Akopova, T. A.
AU  - Markvicheva, E. A.
AU  - Chernyshenko, A. O.
AU  - Zelenetski, A. N.
AU  - Pandit, S. S.
AU  - 
VL  - 699
UR  - 
SN  - 978-1-4419-7270-5
DO  - 10.1007/978-1-4419-7270-5_6
AB  - Multi-component reactions of building blocks with more than one MCR-reactive group will give rise to oligomeric MCR products. The proper choice of at least two bifunctional building blocks will give either a polymeric or a cyclic product. Apart from polymerization, repetitive or consecutive Ugi reactions have been used to produce linear MCR-heterooligomers with such building blocks.
A2  - Mironov, M. A., ed.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 98
TI  - Chalcogen-Based Organocatalysis
T2  - Enantioselective Organocatalyzed Reactions I
PB  - 
PY  - 2011
SP  - 209-314
AU  - Wessjohann, L. A.
AU  - Nin Brauer, M. C.
AU  - Brand, K.
AU  - 
VL  - 
UR  - 
SN  - 978-90-481-3865-4
DO  - 10.1007/978-90-481-3865-4_7
AB  - Most current organocatalysts are based on nitrogen (or phosphorus) as reactive atom, including also most processes depending on proton acidity and/or Lewis basicity. Only few organocatalytic systems use organochalcogens, although such reactions are of great importance in nature, especially evident in hydrolases with serine or cysteine as catalytic hotspot, or in oxidoreductases with cysteine or selenocysteine as key players. Catalytic processes in nature commonly rely on the nucleophilic or redox properties of chalcogen atoms. Accordingly early attempts in chemical catalysis using organochalcogens concentrate either on systems reminiscent of catalytic diads and triads of enzymes with catalysts consisting of a hydroxyl or sulfhydryl group that is activated as nucleophile by a neighboring base (catalytic diads and triads). Other “traditional” uses of chalcogen-based catalysts comprise chiral dioxiranes and oxaziranes for epoxidations, and sulfur redox catalysts, the latter especially in the application of sulfur ylides covered by the predominant work of Aggarwal et al. Since the advent of “Organocatalysis” as a distinct subfield of catalysis, not only these traditional organochalcogen catalyst systems excelled; also new applications are more systematically studied now, including not only oxygen and sulfur but increasingly selenium – and to a smaller extent – even tellurium based catalysis [372]. If nature and its several thousand years of selection of catalysis modes serve as a reference, group VI-based catalysis is yet very much below its real potential in chemical organocatalysis. This contribution thus aims at giving the reader an entry into this so much underutilized field, which offers ample room especially for those who like to try new paths and who not only wish expand on existing processes of well ­established nitrogen-based catalysts.
A2  - Mahrwald, R., ed.
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1597
TI  - Enantiodivergente Organokaskadenreaktionen
JO  - Angew. Chem.
PY  - 2010
SP  - 858-861
AU  - Westermann, B.
AU  - Ayaz, M.
AU  - van Berkel, S.
AU  - 
VL  - 122
UR  - 
DO  - 10.1002/ange.200904638
AB  - In der Synthese strukturell und stereochemisch komplexer Moleküle mithilfe von Organokaskadenreaktionen können Katalysatoren auf enantiodivergente Weise wirken. Ein Beispiel ist der asymmetrische Aufbau quartärer Kohlenstoffzentren über komplementäre Enamin/Iminium‐Katalysen (siehe Schema; En=Enaminaktivierung, Im=Iminiumaktivierung).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1596
TI  - Enantiodivergent Organocascade Reactions
JO  - Angew. Chem. Int. Ed.
PY  - 2010
SP  - 846-849
AU  - Westermann, B.
AU  - Ayaz, M.
AU  - van Berkel, S.
AU  - 
VL  - 49
UR  - 
DO  - 10.1002/anie.200904638
AB  - By targeting structural and stereochemical complexity with organocascade reactions, distinct catalysts can form molecular frameworks in an enantiodivergent way. This goal was elegantly achieved for the asymmetric synthesis of quaternary carbon centers by two complementary routes employing cascades of either enamine or iminium catalysis (see scheme; En=enamine activation, Im=iminium activation).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1588
TI  - Synthesis, characterization and reactivity of carbohydrate platinum(IV) complexes with thioglycoside ligands
JO  - Dalton Trans.
PY  - 2010
SP  - 6327-6338
AU  - Vetter, C.
AU  - Pornsuriyasak, P.
AU  - Schmidt, J.
AU  - Rath, N. P.
AU  - Rüffer, T.
AU  - Demchenko, A. V.
AU  - Steinborn, D.
AU  - 
VL  - 39
UR  - 
DO  - 10.1039/B927058B
AB  - Reactions of fac-[PtMe3(4,4′-R2bpy)(Me2CO)][BF4] (R = H, 1a; tBu, 1b) and fac-[PtMe3(OAc-κ2O,O′)(Me2CO)] (2), respectively, with thioglycosides containing thioethyl (ch-SEt) and thioimidate (ch-STaz, Taz = thiazoline-2-yl) anomeric groups led to the formation of the carbohydrate platinum(IV) complexes fac-[PtMe3(4,4′-R2bpy)(ch*)][BF4] (ch* = ch-SEt, 8–14; ch-STaz, 15–23) and fac-[PtMe3(OAc-κ2O,O′)(ch*)] (ch* = ch-SEt, 24–28; ch-STaz = 29–35), respectively. NMR (1H, 13C, 195Pt) spectroscopic investigations and a single-crystal X-ray diffraction analysis of 19 (ch-STaz = 2-thiazolinyl 2,3,4,6-tetra-O-benzoyl-1-thio-β-D-galactopyranose) revealed the S coordination of the ch-SEt glycosides and the N coordination of the ch-STaz glycosides. Furthermore, X-ray structure analyses of the two decomposition products fac-[PtMe3(bpy)(STazH-κS)][BF4] (21a) and 1,6-anhydro-2,3,4-tri-O-benzoyl-β-D-glucopyranose (23a), where a cleavage of the anomeric C–S bond had occurred in both cases, gave rise to the assumption that this decomposition was mediated due to coordination of the thioglycosides to the high electrophilic platinum(IV) atom, in non-strictly dried solutions. Reactions of fac-[PtMe3(Me2CO)3][BF4] (3) with ch-SEt as well as with ch-SPT and ch-Sbpy thioglycosides (PT = 4-(pyridine-2-yl)-thiazole-2-yl; bpy = 2,2′-bipyridine-6-yl), having N,S and N,N heteroaryl anomeric groups, respectively, led to the formation of platinum(IV) complexes of the type fac-[PtMe3(ch*)][BF4] (ch* = ch-SEt, 36–40, ch-SPT 42–44, ch-Sbpy45, 46). The thioglycosides were found to be coordinated in a tridentate κS,κ2O,O′, κS,κN,κO and κS,κ2N,N′ coordination mode, respectively. Analogous reactions with ch-STaz ligands succeeded for 2-thiazolinyl 2,3,4-tri-O-benzyl-6-O-(2,2′-bipyridine-6-yl)-1-thio-β-D-glucopyranoside (5h) resulting in fac-[PtMe3(ch-STaz)][BF4] (41, ch-STaz = 5h), having a κ3N,N′,N′′coordinated thioglycoside ligand.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1587
TI  - Synthesis, characterization and in vitro cytotoxicity studies of platinum(IV) complexes with thiouracil ligands
JO  - Inorg. Chim. Acta
PY  - 2010
SP  - 2452-2460
AU  - Vetter, C.
AU  - Kaluđerović, G. N.
AU  - Paschke, R.
AU  - Kluge, R.
AU  - Schmidt, J.
AU  - Steinborn, D.
AU  - 
VL  - 363
UR  - 
DO  - 10.1016/j.ica.2010.03.079
AB  - Reactions of [PtMe3(bpy)(Me2CO)][BF4] (2) with the thionucleobases 2-thiouracil (s2Ura), 4-thiouracil (s4Ura) and 2,4-dithiouracil (s2s4Ura) resulted in the formation of complexes of the type [PtMe3(bpy)(L-κS)][BF4] (L = s2Ura, 3; s4Ura, 4; s2s4Ura, 5). The complexes were characterized by NMR spectroscopy (1H, 13C, 195Pt), IR spectroscopy as well as microanalyses. The coordination through the C4S groups (4, 5) was additionally confirmed by DFT calculations, where it was shown that these complexes [PtMe3(bpy)(L-κS4)]+ (L = s4Ura, s2s4Ura) are about 5.8 (4b) and 3.3 kcal/mol (5b), respectively, more stable than the respective complexes, having thiouracil ligands bound through the C2X groups (X = O, 4a; S, 5a). For [PtMe3(bpy)(s2Ura-κS2)][BF4] (3) no preferred coordination mode could be assigned solely based on DFT calculations. Analysis of NMR spectra showed the κS2 coordination. In vitro cytotoxic studies of complexes 3−5 on nine different cell lines (8505C, A253, FaDu, A431, A549, A2780, DLD-1, HCT-8, HT-29) revealed in most cases moderate activities. However, 3 and 5 showed significant activity towards A549 and A2780, respectively, possessing IC50 values comparable to those of cisplatin. Cell cycle perturbations and trypan blue exclusion test on cancer cell line A431 using [PtMe3(bpy)(s2s4Ura-κS4)][BF4] (5) showed induction of apoptotic cell death. Furthermore, the reaction of [PtMe3(OAc-κ2O,O′)(Me2CO)] (6) with 4-thiouracil yielded the dinuclear complex [(PtMe3)2(μ-s4Ura–H)2] (7), which has been characterized by microanalysis, NMR (1H, 13C, 195Pt) and IR spectroscopy as well as ESI mass spectrometry. X-ray diffraction analysis of crystals yielded in an isolated case exhibited the presence of a hexanuclear thiouracilato platinum(IV) complex, possessing each three different kinds of methyl platinum(IV) moieties and 4-thiouracilato ligands. This exhibited the ability of 4-thiouracil platinum(IV) complexes to form multinuclear complexes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1582
TI  - Forty-third annual meeting of the German Society for Mass Spectrometry
JO  - Anal. Bioanal. Chem.
PY  - 2010
SP  - 2777-2778
AU  - Sinz, A.
AU  - Schmidt, J.
AU  - 
VL  - 398
UR  - 
DO  - 10.1007/s00216-010-4216-4
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1581
TI  - Comparison of impurity profiles of Orlistat pharmaceutical products using HPLC tandem mass spectrometry
JO  - J. Pharm. Biomed. Anal.
PY  - 2010
SP  - 767-772
AU  - Schneider, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 53
UR  - 
DO  - 10.1016/j.jpba.2010.05.010
AB  - HPLC-UV and MS/MS studies of impurity profiles of original (Xenical®, F. Hoffmann-La Roche Ltd., Switzerland) and generic (Cobese™, Ranbaxy Laboratories Limited, India, and Orsoten, KRKA, Russia) products were carried out. The drug and related impurities were extracted by dissolving commercial samples in ethanol. The generic formulations contained higher levels of impurities than the original product. Impurity profiles (HPLC-MS/MS) of the generic samples are similar among themselves, whilst different in comparison to the impurity profile of the original product. The number of detected impurities for generics (14 impurities in Cobese™ and 13 impurities in Orsoten) is higher than for the original product (3 impurities in Xenical®). Based on these analyses the overall analytical quality follows the order Xenical® (best) &gt; Orsoten &gt; Cobese™.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1576
TI  - Ceanothane and Lupane Type Triterpenes from Zizyphus joazeiro – An Anti-Staphylococcal Evaluation
JO  - Planta Med.
PY  - 2010
SP  - 47-52
AU  - Ramos Leal, I. C.
AU  - Netto dos Santos, K. R.
AU  - Itabaiana Júnior, I.
AU  - Ceva Antunes, O. A.
AU  - Porzel, A.
AU  - Wessjohann, L.
AU  - Machado Kuster, R.
AU  - 
VL  - 76
UR  - 
DO  - 10.1055/s-0029-1185947
AB  - The present paper describes the phytochemical and anti-staphylococcal activity investigation of the dichloromethane extract of the Brazilian plant Zizyphus joazeiro Mart. The purification steps were guided by bioassays against 17 bacterial strains of clinical sources, including methicillin-resistant (MRSA) and ‐sensitive (MSSA) Staphylococcus aureus as well as MRSA (ATCC 33591) and MSSA (ATCC 29213) reference strains. One of the more active fractions is comprised of three lupane-type triterpenes, the methylbetulinate (1) as well as the known betulinic (2) and alphitolic (3) acids and, for the first time in the Z. joazeiro, two ceanothane type triterpenes, the methylceanothate (4) and the epigouanic acid A (5). These substances were assayed against one clinical (PVL+) and the reference strains of S. aureus as well as the ATTC 12228 strain of S. epidermidis, in concentrations that varied from 128 to 0.125 µg/mL in order to establish the minimum inhibitory concentration (MIC) of the drugs. The minimum bactericide concentration (MBC) was also evaluated to distinguish the bactericidal from bacteriostatic activity of the crude fractions and single compounds. Compounds 3 and 4 possess the highest antibacterial activity. They inhibit all bacteria tested at 32 µg/mL and 16 µg/mL, respectively, while the other compounds showed no activity at 128 µg/mL. In contrast to single compounds, the triterpenoid fraction showed bactericidal activity at 256 µg/mL. Structural elucidations are based on 1D and 2D NMR spectroscopy as well as HR‐FT‐ICR‐MS experiments.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1575
TI  - Ampullosine, a new Isoquinoline Alkaloid from Sepedonium ampullosporum (Ascomycetes)
JO  - Nat. Prod. Commun.
PY  - 2010
SP  - 869-872
AU  - Quang, D. N.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Wessjohann, L.
AU  - Haid, M.
AU  - Arnold, N.
AU  - 
VL  - 5
UR  - 
DO  - 10.1177/1934578X1000500609
AB  - A new isoquinoline alkaloid, ampullosine (3-methyl-isoquinoline-6-carboxylic acid, 1), was isolated from Sepedonium ampullosporum and characterized by spectroscopic analysis and chemical reactions. This compound is responsible for the deep yellow color of the culture fluid of this species. Moreover, the known compounds sepedonin (2) and anhydrosepedonin (3) were detected. Twelve strains belonging to eight species of Sepedonium have been screened for these three metabolites by LC/ESI-SRM (selected reaction monitoring). Ampullosine (1) could be detected in almost all species in Sepedonium, but not in the phylogenetically more distant species S. brunneum and S. tulasneanum. Anhydrosepedonin (3) showed antifungal activity against the phytopathogenic fungus Cladosporium cucumerinum.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1574
TI  - Kleine, ungewöhnliche Peptide gegen Krebs
JO  - Nachr. Chem.
PY  - 2010
SP  - 526-532
AU  - Preusentanz, R.
AU  - Pando, O.
AU  - Wessjohann, L.
AU  - 
VL  - 58
UR  - 
DO  - 10.1002/nadc.201069166
AB  - N‐alkylierte Peptide wie die Dolastatine und vor allem die jüngeren Tubulysine gelten als vielversprechende Leitsubstanzen für die Krebstherapie. Konjugate der Tubulysine vereinen Tumorselektivität und Aktivität in bisher nicht bekanntem Maß.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1572
TI  - UBIAD1 Mutation Alters a Mitochondrial Prenyltransferase to Cause Schnyder Corneal Dystrophy
JO  - PLOS ONE
PY  - 2010
SP  - e10760
AU  - Nickerson, M. L.
AU  - Kostiha, B. N.
AU  - Brandt, W.
AU  - Fredericks, W.
AU  - Xu, K.-P.
AU  - Yu, F.-S.
AU  - Gold, B.
AU  - Chodosh, J.
AU  - Goldberg, M.
AU  - Lu, D. W.
AU  - Yamada, M.
AU  - Tervo, T. M.
AU  - Grutzmacher, R.
AU  - Croasdale, C.
AU  - Hoeltzenbein, M.
AU  - Sutphin, J.
AU  - Malkowicz, S. B.
AU  - Wessjohann, L.
AU  - Kruth, H. S.
AU  - Dean, M.
AU  - Weiss, J. S.
AU  - 
VL  - 5
UR  - 
DO  - 10.1371/journal.pone.0010760
AB  - BackgroundMutations in a novel gene, UBIAD1, were recently found to cause the autosomal dominant eye disease Schnyder corneal dystrophy (SCD). SCD is characterized by an abnormal deposition of cholesterol and phospholipids in the cornea resulting in progressive corneal opacification and visual loss. We characterized lesions in the UBIAD1 gene in new SCD families and examined protein homology, localization, and structure.Methodology/Principal FindingsWe characterized five novel mutations in the UBIAD1 gene in ten SCD families, including a first SCD family of Native American ethnicity. Examination of protein homology revealed that SCD altered amino acids which were highly conserved across species. Cell lines were established from patients including keratocytes obtained after corneal transplant surgery and lymphoblastoid cell lines from Epstein-Barr virus immortalized peripheral blood mononuclear cells. These were used to determine the subcellular localization of mutant and wild type protein, and to examine cholesterol metabolite ratios. Immunohistochemistry using antibodies specific for UBIAD1 protein in keratocytes revealed that both wild type and N102S protein were localized sub-cellularly to mitochondria. Analysis of cholesterol metabolites in patient cell line extracts showed no significant alteration in the presence of mutant protein indicating a potentially novel function of the UBIAD1 protein in cholesterol biochemistry. Molecular modeling was used to develop a model of human UBIAD1 protein in a membrane and revealed potentially critical roles for amino acids mutated in SCD. Potential primary and secondary substrate binding sites were identified and docking simulations indicated likely substrates including prenyl and phenolic molecules.Conclusions/SignificanceAccumulating evidence from the SCD familial mutation spectrum, protein homology across species, and molecular modeling suggest that protein function is likely down-regulated by SCD mutations. Mitochondrial UBIAD1 protein appears to have a highly conserved function that, at least in humans, is involved in cholesterol metabolism in a novel manner.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1600
TI  - Profiling of phenylpropanoids in transgenic low-sinapine oilseed rape (Brassica napus)
JO  - Phytochemistry
PY  - 2010
SP  - 1076-1084
AU  - Wolfram, K.
AU  - Schmidt, J.
AU  - Wray, V.
AU  - Milkowski, C.
AU  - Schliemann, W.
AU  - Strack, D.
AU  - 
VL  - 71
UR  - 
DO  - 10.1016/j.phytochem.2010.04.007
AB  - A dsRNAi approach silencing a key enzyme of sinapate ester biosynthesis (UDP-glucose:sinapate glucosyltransferase, encoded by the UGT84A9 gene) in oilseed rape (Brassica napus) seeds was performed to reduce the anti-nutritive properties of the seeds by lowering the content of the major seed component sinapine (sinapoylcholine) and various minor sinapate esters. The transgenic seeds have been produced so far to the T6 generation and revealed a steady suppression of sinapate ester accumulation. HPLC analysis of the wild-type and transgenic seeds revealed, as in the previous generations, marked alterations of the sinapate ester pattern of the transformed seeds. Besides strong reduction of the amount of the known sinapate esters, HPLC analysis revealed unexpectedly the appearance of several minor hitherto unknown rapeseed constituents. These compounds were isolated and identified by mass spectrometric and NMR spectroscopic analyses. Structures of 11 components were elucidated to be 4-O-glucosides of syringate, caffeyl alcohol and its 7,8-dihydro derivative as well as of sinapate and sinapine, along with sinapoylated kaempferol glycosides, a hexoside of a cyclic spermidine alkaloid and a sinapine derivative with an ether-bridge to a C6–C3-unit. These results indicate a strong impact of the transgenic approach on the metabolic network of phenylpropanoids in B. napus seeds. Silencing of UGT84A9 gene expression disrupt the metabolic flow through sinapoylglucose and alters the amounts and nature of the phenylpropanoid endproducts.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1561
TI  - In Vitro Plants, Callus and Root Cultures of Plumbago indica and Their Biosynthetic Potential for Plumbagin
JO  - King Mongkut\'s Agro-Industry Journal
PY  - 2010
SP  - 53-65
AU  - Jindaprasert, A.
AU  - Samappito, S.
AU  - Springob, K.
AU  - Schmidt, J.
AU  - Gulder, T.
AU  - De-Eknamkul, W.
AU  - Bringmann, G.
AU  - Kutchan, T. M.
AU  - 
VL  - 2
UR  - 
AB  - In vitro cultured plants of Plumbago indica L. were established from nodal segments and micropropagated on hormone-free LS medium. These in vitro plantlets produced plumbagin with the content 0.79-0.87 mg g-1 dry weight which was more than half of the content found in the whole roots of greenhouse plants. Root and callus cultures were also initiated from stem and young leaf explants, respectively. The root cultures maintained in hormone-free MS medium accumulated 0.28 mg g-1 plumbagin whereas the callus cultures grown on MS medium supplemented with 1.0 mg l-1 2,4-dichloropenoxyacetic acid (2,4-D) and 0.1 mg l-1 kinetin contained only 0.013 mg g-1 of the compound. In addition to plumbagin, its related compounds plumbagic acid and plumbagic acid glucoside were also found specifically in the root tissues of the micropropagated plantlets and the root cultures. These results suggested the biosynthetic potential for the plumbagin-derived compounds in the tissues of in vitro plants and organ cultures which allows us to use them as materials for studying genes and enzymes involved in the naphthoquinone formation in P. indica.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1557
TI  - Photoaffinity-Labeled Peptoids and Depsipeptides by Multicomponent Reactions
JO  - Synthesis
PY  - 2010
SP  - 2997-3003
AU  - Henze, M.
AU  - Kreye, O.
AU  - Brauch, S.
AU  - Nitsche, C.
AU  - Naumann, K.
AU  - Wessjohann, L. A.
AU  - Westermann, B.
AU  - 
VL  - 2010
UR  - 
DO  - 10.1055/s-0030-1258182
AB  - Photoaffinity tags can be incorporated easily into peptoids and congeners by the Ugi and Passerini multicomponent reactions. Products related to photo-methionine and photo-leucine can be accomplished by diazirine-containing building blocks. The same protocols can be used to synthesize derivatives with benzophenone photo cross-linkers.
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions
ER  - 


TY  - JOUR
ID  - 1554
TI  - Breakdown products of neoglucobrassicin inhibit activation of Nrf2 target genes mediated by myrosinase-derived glucoraphanin hydrolysis products
JO  - Biol. Chem.
PY  - 2010
SP  - 1281-1293
AU  - Haack, M.
AU  - Löwinger, M.
AU  - Lippmann, D.
AU  - Kipp, A.
AU  - Pagnotta, E.
AU  - Iori, R.
AU  - Monien, B. H.
AU  - Glatt, H.
AU  - Brauer, M. N.
AU  - Wessjohann, L. A.
AU  - Brigelius-Flohé, R.
AU  - 
VL  - 391
UR  - 
DO  - 10.1515/bc.2010.134
AB  - Glucosinolates (GLSs) present in Brassica vegetables serve as precursors for biologically active metabolites, which are released by myrosinase and induce phase 2 enzymes via the activation of Nrf2. Thus, GLSs are generally considered beneficial. The pattern of GLSs in plants is various, and contents of individual GLSs change with growth phase and culture conditions. Whereas some GLSs, for example, glucoraphanin (GRA), the precursor of sulforaphane (SFN), are intensively studied, functions of others such as the indole GLS neoglucobrassicin (nGBS) are rather unknown as are functions of combinations thereof. We therefore investigated myrosinase-treated GRA, nGBS and synthetic SFN for their ability to induce NAD(P)H:quinone oxidoreductase 1 (NQO1) as typical phase 2 enzyme, and glutathione peroxidase 2 (GPx2) as novel Nrf2 target in HepG2 cells. Breakdown products of nGBS potently inhibit both GRA-mediated stimulation of NQO1 enzyme and Gpx2 promoter activity. Inhibition of promoter activity depends on the presence of an intact xenobiotic responsive element (XRE) and is also observed with benzo[a]pyrene, a typical ligand of the aryl hydrocarbon receptor (AhR), suggesting that suppressive effects of nGBS are mediated via AhR/XRE pathway. Thus, the AhR/XRE pathway can negatively interfere with the Nrf2/ARE pathway which has consequences for dietary recommendations and, therefore, needs further investigation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1553
TI  - Acetylcholinesterase inhibitors from the toadstool Cortinarius infractus
JO  - Bioorg. Med. Chem.
PY  - 2010
SP  - 2173-2177
AU  - Geissler, T.
AU  - Brandt, W.
AU  - Porzel, A.
AU  - Schlenzig, D.
AU  - Kehlen, A.
AU  - Wessjohann, L.
AU  - Arnold, N.
AU  - 
VL  - 18
UR  - 
DO  - 10.1016/j.bmc.2010.01.074
AB  - Inhibition of acetylcholinesterase (AChE) and therefore prevention of acetylcholine degradation is one of the most accepted therapy opportunities for Alzheimer´s disease (AD), today. Due to lack of selectivity of AChE inhibitor drugs on the market, AD-patients suffer from side effects like nausea or vomiting. In the present study the isolation of two alkaloids, infractopicrin (1) and 10-hydroxy-infractopicrin (2), from Cortinarius infractus Berk. (Cortinariaceae) is presented. Both compounds show AChE-inhibiting activity and possess a higher selectivity than galanthamine. Docking studies show that lacking π–π-interactions in butyrylcholinesterase (BChE) are responsible for selectivity. Studies on other AD pathology related targets show an inhibitory effect of both compounds on self-aggregation of Aβ-peptides but not on AChE induced Aβ-peptide aggregation. Low cytotoxicity as well as calculated pharmacokinetic data suggest that the natural products could be useful candidates for further drug development.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1547
TI  - Synthesis and Selective Anticancer Activity of Organochalcogen Based Redox Catalysts
JO  - J. Med. Chem.
PY  - 2010
SP  - 6954-6963
AU  - Doering, M.
AU  - Ba, L. A.
AU  - Lilienthal, N.
AU  - Nicco, C.
AU  - Scherer, C.
AU  - Abbas, M.
AU  - Zada, A. A. P.
AU  - Coriat, R.
AU  - Burkholz, T.
AU  - Wessjohann, L.
AU  - Diederich, M.
AU  - Batteux, F.
AU  - Herling, M.
AU  - Jacob, C.
AU  - 
VL  - 53
UR  - 
DO  - 10.1021/jm100576z
AB  - Many tumor cells exhibit a disturbed intracellular redox state resulting in higher levels of reactive oxygen species (ROS). As these contribute to tumor initiation and sustenance, catalytic redox agents combining significant activity with substrate specificity promise high activity and selectivity against oxidatively stressed malignant cells. We describe here the design and synthesis of novel organochalcogen based redox sensor/effector catalysts. Their selective anticancer activity at submicromolar and low micromolar concentrations was established here in a range of tumor entities in various biological systems including cell lines, primary tumor cell cultures, and animal models. In the B-cell derived chronic lymphocytic leukemia (CLL), for instance, such compounds preferentially induce apoptosis in the cancer cells while peripheral blood mononuclear cells (PBMC) from healthy donors and the subset of normal B-cells remain largely unaffected. In support of the concept of sensor/effector based ROS amplification, we are able to demonstrate that underlying this selective activity against CLL cells are pre-existing elevated ROS levels in the leukemic cells compared to their nonmalignant counterparts. Furthermore, the catalysts act in concert with certain chemotherapeutic drugs in several carcinoma cell lines to decrease cell proliferation while showing no such interactions in normal cells. Overall, the high efficacy and selectivity of (redox) catalytic sensor/effector compounds warrant further, extensive testing toward transfer into the clinical arena.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1540
TI  - Diallylpolysulfides induce growth arrest and apoptosis
JO  - Int. J. Oncol.
PY  - 2010
SP  - 743-749
AU  - Busch, C.
AU  - Jacob, C.
AU  - Anwar, A.
AU  - Burkholz, T.
AU  - Ba, L. A.
AU  - Cerella, C.
AU  - Diederich, M.
AU  - Brandt, W.
AU  - Wessjohann, L.
AU  - Montenarh, M.
AU  - 
VL  - 36
UR  - 
DO  - 10.3892/ijo_00000550
AB  - Garlic-derived organo sulphur compounds such as diallylsulfides provide a significant protection against carcinogenesis. Chemically synthesized, and highly pure diallylsulfides with a chain of 1-4 sulphur atoms, as well as a range of control compounds, were employed to investigate the influence of these agents on cell viability, cell cycle arrest and induction of apoptosis in HCT116 human colon cancer cells. Diallyltrisulfide, and even more efficiently diallyltetrasulfide treatment of HCT116 cells led to a reduced cell viability, cell cycle arrest and apoptosis. A similar activity was found for the propyl-analogues, while mono- and disulfides were considerably less active. Initial calculations point toward the ability of tri- and tetrasulfides to form reactive oxygen species (ROS). Here, we found that the induction of apoptosis was indeed dependent on the redox-state of the cell, with anti-oxidants being able to prevent sulfide-induced apoptosis. Furthermore, using HCT116 cells which were either positive or negative for p53 revealed that p53 is clearly dispensable for induction of apoptosis. Growth arrest and induction of apoptosis is associated with a considerable reduction of the level of cdc25C. These results support the therapeutic potential of polysulfides and allow insight into the mechanisms based on the polysulfide biochemistry.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1535
TI  - Chemoinformatic Analysis of Biologically Active Macrocycles
JO  - Curr. Top. Med. Chem.
PY  - 2010
SP  - 1361-1379
AU  - Brandt, W.
AU  - Haupt, V. J.
AU  - Wessjohann, L. A.
AU  - 
VL  - 10
UR  - 
DO  - 10.2174/156802610792232060
AB  - In this review, macrocycles are defined as organic molecules containing at least one non-bridged cycle of 12 or more covalently connected atoms. Common statistical aspects as well as structure activity relationships (SAR) of macrocycles based on chemoinformatics methods are discussed. Can macrocyclic structural features be linked to activities against cancer cells, viruses like HIV, or bacteria? General challenges and problems in using chemoinformatics for more detailed analyses of macrocycles based on large compound databases are outlined.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1534
TI  - Straightforward Method for the Synthesis of Selenocysteine and Selenocystine Derivatives from L-Serine Methyl Ester
JO  - Synthesis
PY  - 2010
SP  - 3131-3137
AU  - Braga, A. L.
AU  - Wessjohann, L. A.
AU  - Taube, P. S.
AU  - Galetto, F. Z.
AU  - de Andrade, F. M.
AU  - 
VL  - 2010
UR  - 
DO  - 10.1055/s-0030-1258188
AB  - A set of selenoamino acids has been efficiently synthesized under smooth conditions by a simple, flexible and modular strategy. In this method, O-mesylated l-serine methyl ester is generated in situ and directly substituted with various selenolate anions to afford selenocysteine, selenolanthionine, and selenocystine derivatives in good yields. Also, a tellurocysteine derivative can be obtained by this method.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1533
TI  - On the Reactivity of Rhodium(I) Complexes with κP-Coordinated γ-Phosphino-Functionalized Propyl Phenyl Sulfide Ligands: Routes to Cyclic Rhodium Complexes with κC,κP- and κP,κS-Coordinated Ligands as Well as Bis(diphenylphosphino)methanide Ligands
JO  - Organometallics
PY  - 2010
SP  - 6749-6762
AU  - Block, M.
AU  - Kluge, T.
AU  - Bette, M.
AU  - Schmidt, J.
AU  - Steinborn, D.
AU  - 
VL  - 29
UR  - 
DO  - 10.1021/om100878n
AB  - Reactions of dinuclear μ-chlorido rhodium(I) complexes [(RhL2)2(μ-Cl)2] (L2 = cycloocta-1,5-diene, cod, 3; L2 = P∧P: Ph2PCH2PPh2, dppm, 4a; Ph2P(CH2)2PPh2, dppe, 4b; Ph2P(CH2)3PPh2, dppp, 4c; Me2P(CH2)2PMe2, dmpe, 4d) with γ-phosphino-functionalized propyl phenyl sulfides PhSCH2CH2CH2PR2 (R = Ph, 1; Cy, 2) afforded mononuclear rhodium(I) complexes of the type [RhCl(R2PCH2CH2CH2SPh-κP)L2] ] (R = Ph/L2 = P∧P, 5a−c; R = Ph/L2 = cod, 6; R = Cy/L2 = P∧P, 7a−d; R = Cy/L2 = cod, 8). Single-crystal X-ray diffraction analysis of 7b·C6H6 exhibited the expected square-planar coordination of the rhodium atom having coordinated dppe-κ2P,P′, Cy2PCH2CH2CH2SPh-κP, and a chlorido ligand. Deprotonation of complexes 5b/c, 6, 7b/c, and 8 with lithium diisopropyl amide (LDA) yielded, with a selective deprotonation of the CH2 group next to the sulfur atom (α-CH2 group), complexes of the type [Rh{CH(SPh)CH2CH2PR2-κC,κP}L2] (13b/c, 14, 15b/c, 16), thus being organorhodium intramolecular coordination compounds. Unexpectedly, reactions of the dppm complexes 5a and 7a with LDA led to deprotonation of the CH2 group of the dppm ligand, resulting in formation of mononuclear rhodium complexes with a bis(diphenylphosphino)methanide-κ2P,P′ ligand and a R2P∧SPh-κP,κS ligand, as well (17, 18). Single-crystal X-ray diffraction analysis of [Rh(dppm−H-κ2P,P′)(Cy2PCH2CH2CH2SPh-κP,κS)]·THF (18·THF) shows the rhodium atom located in the center of a distorted square-planar environment having bound the P∧S-κP,κS ligand and the anionic dppm−H-κ2P,P′ ligand with a very small P2−Rh−P3 angle (68.8(2)°) reflecting the small bite of that ligand. Addition of Tl[PF6] to complexes 5−8 afforded cationic rhodium(I) complexes of the type [Rh(R2PCH2CH2CH2SPh-κP,κS)L2][PF6] (9−12) bearing bidentately coordinated neutral co-ligands (P∧P: 9, 11; cod, 10, 12) and κP,κS-coordinated γ-phosphino-functionalized propyl phenyl sulfide ligands, as well. Single-crystal X-ray diffraction analysis of 10 reveals that the rhodium atom adopts a slightly distorted square-planar conformation. Complexes 9a−c and 11a−d were found to react with carbon monoxide, yielding cationic rhodium carbonyl complexes [Rh(CO)(R2PCH2CH2CH2SPh-κP,κS)(P∧P-κ2P,P′)]+ (19, 20), being in a dynamic equilibrium between two diastereomers each at room temperature, which was additionally verified by DFT calculations.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1531
TI  - Enantioenriched Naphthoquinone Mannich Bases by Organocatalyzed Nucleophilic Additions to in situ Formed Imines
JO  - Synlett
PY  - 2010
SP  - 1489-1492
AU  - Ayaz, M.
AU  - Westermann, B.
AU  - 
VL  - 2010
UR  - 
DO  - 10.1055/s-0029-1219946
AB  - Organocatalytic nucleophilic addition of 2-hydroxylnaphthaquinone to imines is reported. This new route can be used to produce enantioenriched Mannich bases with excellent yields and moderate enantioselectivities.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1537
TI  - Seven-component reactions by sequential chemoselective Ugi–Mumm/Ugi–Smiles reactions
JO  - Chem. Commun.
PY  - 2010
SP  - 3387-3389
AU  - Brauch, S.
AU  - Gabriel, L.
AU  - Westermann, B.
AU  - 
VL  - 46
UR  - 
DO  - 10.1039/B927388C
AB  - A seven-component reaction was accomplished by utilizing the different chemoselectivities of the Ugi–Mumm and the Ugi–Smiles reaction. The sequential multicomponent reactions led to highly diverse peptide and glycopeptide like structures.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1536
TI  - The membrane bound aromatic p-hydroxybenzoic acid oligoprenyltransferase (UbiA) - how iterative improvements lead to a realistic structure that offers new insights into functional aspects of prenyl transferases and terpene synthases
JO  - J. Cheminform.
PY  - 2010
SP  - O20
AU  - Brandt, W.
AU  - Kufka, J.
AU  - Schulze, D.
AU  - Schulze, E.
AU  - Rausch, F.
AU  - Wessjohann, L.
AU  - 
VL  - 2
UR  - 
DO  - 10.1186/1758-2946-2-S1-O20
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 101
TI  - Cyclic Peptidomimetics and Pseudopeptides from Multicomponent Reactions
T2  - Synthesis of Heterocycles via Multicomponent Reactions I
PB  - Top. Heterocycl. Chem.
PY  - 2010
SP  - 199-226
AU  - Wessjohann, L. A.
AU  - Rhoden, C. R. B.
AU  - Rivera, D. G.
AU  - Vercillo, O. E.
AU  - 
VL  - 23
UR  - 
SN  - 978-3-642-12675-8
DO  - 10.1007/7081_2009_25
AB  - Multicomponent reactions (MCRs) that provide in the final product amides are suitable to produce peptides and peptide-like moieties. The Passerini and Staudinger reactions provide one amide bond, and the Ugi-four-component reaction generates two amides from three or even four (or more) components, respectively. The Ugi-reaction thus is most important to produce peptides and peptoids while the Passerini reaction is useful to generate depsipeptoid moieties. In order to produce cyclic peptides and pseudopeptides, the linear peptidic MCR products have to be cyclized, usually with the help of bifunctional or activatable building blocks. Orthogonal but cyclizable secondary functionalities that need no protection in isonitrile MCRs commonly include alkenes (for ring closing metathesis), azide/alkyne (for Huisgen click reactions) or dienes and enoates (Diels-Alder) etc. If MCR-reactive groups are to be used also for the cyclisation, monoprotected bifunctional building blocks are used and deprotected after the MCR, e.g. for Ugi reactions as Ugi-Deprotection-Cyclisation (UDC). Alternatively one of the former building blocks or functional groups generated by the MCR can be activated. Most commonly these are activated amides (from so-called convertible isonitriles) which can be used e.g. for Ugi-Activation-Cyclisation (UAC) protocols, or most recently for a simultaneous use of both strategies Ugi-Deprotection/Activation-Cyclisation (UDAC). These methods mostly lead to small, medicinally relevant peptide turn mimics. In an opposing strategy, the MCR is rather used as ring-closing reaction, thereby introducing a (di-)peptide moiety. Most recently these processes have been combined to use MCRs for both, linear precursor synthesis and cyclisation. These multiple MCR approaches allow the most efficient and versatile one pot synthesis of macrocyclic pseudopeptides known to date.
A2  - Orru, R. V. A. &amp; Ruijter, E., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1631
TI  - Neuroprotection and enhanced neurogenesis by extract from the tropical plant Knema laurina after inflammatory damage in living brain tissue
JO  - J. Neuroimmunol.
PY  - 2009
SP  - 91-99
AU  - Häke, I.
AU  - Schönenberger, S.
AU  - Neumann, J.
AU  - Franke, K.
AU  - Paulsen-Merker, K.
AU  - Reymann, K.
AU  - Ismail, G.
AU  - bin Din, L.
AU  - Said, I. M.
AU  - Latiff, A.
AU  - Wessjohann, L.
AU  - Zipp, F.
AU  - Ullrich, O.
AU  - 
VL  - 206
UR  - 
DO  - 10.1016/j.jneuroim.2008.10.007
AB  - Inflammatory reactions in the CNS, resulting from a loss of control and involving a network of non-neuronal and neuronal cells, are major contributors to the onset and progress of several major neurodegenerative diseases. Therapeutic strategies should therefore keep or restore the well-controlled and finely-tuned balance of immune reactions, and protect neurons from inflammatory damage. In our study, we selected plants of the Malaysian rain forest by an ethnobotanic survey, and investigated them in cell-based-assay-systems and in living brain tissue cultures in order to identify anti-inflammatory and neuroprotective effects. We found that alcoholic extracts from the tropical plant Knema laurina (Black wild nutmeg) exhibited highly anti-inflammatory and neuroprotective effects in cell culture experiments, reduced NO- and IL-6-release from activated microglia cells dose-dependently, and protected living brain tissue from microglia-mediated inflammatory damage at a concentration of 30 µg/ml. On the intracellular level, the extract inhibited ERK-1/2-phosphorylation, IkB-phosphorylation and subsequently NF-kB-translocation in microglia cells. K. laurina belongs to the family of Myristicaceae, which have been used for centuries for treatment of digestive and inflammatory diseases and is also a major food plant of the Giant Hornbill. Moreover, extract from K. laurina promotes also neurogenesis in living brain tissue after oxygen–glucose deprivation. In conclusion, extract from K. laurina not only controls and limits inflammatory reaction after primary neuronal damage, it promotes moreover neurogenesis if given hours until days after stroke-like injury.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1627
TI  - (+)-7-iso-Jasmonoyl-L-isoleucine is the endogenous bioactive jasmonate
JO  - Nat. Chem. Biol.
PY  - 2009
SP  - 344-350
AU  - Fonseca, S.
AU  - Chini, A.
AU  - Hamberg, M.
AU  - Adie, B.
AU  - Porzel, A.
AU  - Kramell, R.
AU  - Miersch, O.
AU  - Wasternack, C.
AU  - Solano, R.
AU  - 
VL  - 5
UR  - 
DO  - 10.1038/nchembio.161
AB  - Hormone-triggered activation of the jasmonate signaling pathway in Arabidopsis thaliana requires SCFCOI1-mediated proteasome degradation of JAZ repressors. (−)-JA-L-Ile is the proposed bioactive hormone, and SCFCOI1 is its likely receptor. We found that the biological activity of (−)-JA-L-Ile is unexpectedly low compared to coronatine and the synthetic isomer (+)-JA-L-Ile, which suggests that the stereochemical orientation of the cyclopentanone-ring side chains greatly affects receptor binding. Detailed GC-MS and HPLC analyses showed that the (−)-JA-L-Ile preparations currently used in ligand binding studies contain small amounts of the C7 epimer (+)-7-iso-JA-L-Ile. Purification of each of these molecules demonstrated that pure (−)-JA-L-Ile is inactive and that the active hormone is (+)-7-iso-JA-L-Ile, which is also structurally more similar to coronatine. In addition, we show that pH changes promote conversion of (+)-7-iso-JA-L-Ile to the inactive (−)-JA-L-Ile form, thus providing a simple mechanism that can regulate hormone activity through epimerization.
A2  - 
C1  - Bioorganic Chemistry; Molecular Signal Processing
ER  - 


TY  - JOUR
ID  - 1623
TI  - Antioomycete Activity of γ-Oxocrotonate Fatty Acids against P. infestans
JO  - J. Agr. Food Chem.
PY  - 2009
SP  - 9607-9612
AU  - Eschen-Lippold, L.
AU  - Draeger, T.
AU  - Teichert, A.
AU  - Wessjohann, L.
AU  - Westermann, B.
AU  - Rosahl, S.
AU  - Arnold, N.
AU  - 
VL  - 57
UR  - 
DO  - 10.1021/jf902067k
AB  - Infections with Phytophthora infestans, the causal agent of potato and tomato late blight disease, are difficult to control and can lead to considerable agricultural losses. Thus, the development of new effective agents against the pathogen is of great interest. In previous work, (E)-4-oxohexadec-2-enoic acid (3) was isolated from Hygrophorus eburneus, which exhibited fungicidal activity against Cladosporium cucumerinum. Here, the inhibitory effect of 3 on P. infestans spore germination and mycelium growth in vitro is demonstrated. The in vivo effect on infections of whole potato plants was investigated by spraying plants with the sodium salt of 3, sodium (2E)-4-oxohexadec-2-enoic acid (4), prior to P. infestans inoculation. Additionally, the influence of 3 on mycelium growth of Colletotrichum coccodes, the causal agent of potato black dot disease, was analyzed. In all approaches, a significant inhibition of pathogen development was achieved. Importantly, the unsaturated fatty acid exerted no toxic effect when sprayed on plants, a prerequisite for its commercial use.
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions
ER  - 


TY  - JOUR
ID  - 1616
TI  - First Synthesis of Dimethyl-1H-Isochromeno[3,4-b]Carbazoles
JO  - Nat. Prod. Commun.
PY  - 2009
SP  - 
AU  - Cuong, N. M.
AU  - Wilhelm, H.
AU  - Porzel, A.
AU  - Wessjohann, L.
AU  - 
VL  - 4
UR  - 
DO  - 10.1177/1934578X0900400708
AB  - The first synthesis of isochromene fused carbazols, (4aS, 13bR)-2,5,5-trimethyl-3,4,4a,5,8,13b-hexahydroisochromeno[3,4-b]carbazole (2) and its epi-isomer 3 by condensation of citral and 2-hydroxycarbazole using Ti(OEt)4 and MeAlCl2 as catalysts is described.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1613
TI  - Optimization of inhibitors for human glutaminyl cyclase by structure based design and bio-isosteric replacement
JO  - Drug. Future
PY  - 2009
SP  - 186
AU  - Buchholz, M.
AU  - Brandt, W.
AU  - Hoffmann, T.
AU  - Schilling, S.
AU  - Demuth, H.-U.
AU  - Heiser, U.
AU  - 
VL  - 34
UR  - https://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_toc_pr?p_JournalID=2&amp;p_IssueID=1006
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1612
TI  - Inhibitors for Human Glutaminyl Cyclase by Structure Based Design and Bioisosteric Replacement
JO  - J. Med. Chem.
PY  - 2009
SP  - 7069-7080
AU  - Buchholz, M.
AU  - Hamann, A.
AU  - Aust, S.
AU  - Brandt, W.
AU  - Böhme, L.
AU  - Hoffmann, T.
AU  - Schilling, S.
AU  - Demuth, H.-U.
AU  - Heiser, U.
AU  - 
VL  - 52
UR  - 
DO  - 10.1021/jm900969p
AB  - The inhibition of human glutaminyl cyclase (hQC) has come into focus as a new potential approach for the treatment of Alzheimer’s disease. The hallmark of this principle is the prevention of the formation of Aβ3,11(pE)-40,42, as these Aβ-species were shown to be of elevated neurotoxicity and likely to act as a seeding core leading to an accelerated formation of Aβ-oligomers and fibrils. Starting from 1-(3-(1H-imidazol-1-yl)propyl)-3-(3,4-dimethoxyphenyl)thiourea, bioisosteric replacements led to the development of new classes of inhibitors. The optimization of the metal-binding group was achieved by homology modeling and afforded a first insight into the probable binding mode of the inhibitors in the hQC active site. The efficacy assessment of the hQC inhibitors was performed in cell culture, directly monitoring the inhibition of Aβ3,11(pE)-40,42 formation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1611
TI  - Molecular and structural basis of metabolic diversity mediated by prenyldiphosphate converting enzymes
JO  - Phytochemistry
PY  - 2009
SP  - 1758-1775
AU  - Brandt, W.
AU  - Bräuer, L.
AU  - Günnewich, N.
AU  - Kufka, J.
AU  - Rausch, F.
AU  - Schulze, D.
AU  - Schulze, E.
AU  - Weber, R.
AU  - Zakharova, S.
AU  - Wessjohann, L.
AU  - 
VL  - 70
UR  - 
DO  - 10.1016/j.phytochem.2009.09.001
AB  - General thermodynamic calculations using the semiempiric PM3 method have led to the conclusion that prenyldiphosphate converting enzymes require at least one divalent metal cation for the activation and cleavage of the diphosphate–prenyl ester bond, or they must provide structural elements for the efficient stabilization of the intermediate prenyl cation. The most important common structural features, which guide the product specificity in both terpene synthases and aromatic prenyl transferases are aromatic amino acid side chains, which stabilize prenyl cations by cation–π interactions. In the case of aromatic prenyl transferases, a proton abstraction from the phenolic hydroxyl group of the second substrate will enhance the electron density in the phenolic ortho-position at which initial prenylation of the aromatic compound usually occurs.A model of the structure of the integral transmembrane-bound aromatic prenyl transferase UbiA was developed, which currently represents the first structural insight into this group of prenylating enzymes with a fold different from most other aromatic prenyl transferases. Based on this model, the structure–activity relationships and mechanistic aspects of related proteins, for example those of Lithospermum erythrorhizon or the enzyme AuaA from Stigmatella aurantiaca involved in the aurachin biosynthesis, were elucidated. The high similarity of this group of aromatic prenyltransferases to 5-epi-aristolochene synthase is an indication of an evolutionary relationship with terpene synthases (cyclases). This is further supported by the conserved DxxxD motif found in both protein families. In contrast, there is no such relationship to the aromatic prenyl transferases with an ABBA-fold, such as NphB, or to any other known family of prenyl converting enzymes. Therefore, it is possible that these two groups might have different evolutionary ancestors.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1608
TI  - Analysis of phenolic choline esters from seeds of Arabidopsis thaliana and Brassica napus by capillary liquid chromatography/electrospray- tandem mass spectrometry
JO  - J. Mass Spectrom.
PY  - 2009
SP  - 466-476
AU  - Böttcher, C.
AU  - von Roepenack-Lahaye, E.
AU  - Schmidt, J.
AU  - Clemens, S.
AU  - Scheel, D.
AU  - 
VL  - 44
UR  - 
DO  - 10.1002/jms.1522
AB  - Total phenolic choline ester fractions prepared from seeds of Arabidopsis thaliana  and Brassica napus  were analyzed by capillary LC/ESI‐QTOF‐MS and direct infusion ESI‐FTICR‐MS. In addition to the dominating sinapoylcholine, 30 phenolic choline esters could be identified based on accurate mass measurements, interpretation of collision‐induced dissociation (CID) mass spectra, and synthesis of selected representatives. The compounds identified so far include substituted hydroxycinnamoyl‐ and hydroxybenzoylcholines, respective monohexosides as well as oxidative coupling products of phenolic choline esters and monolignols. Phenolic choline esters are well separable by reversed‐phase liquid chromatography and sensitively detectable using electrospray ionization mass spectrometry in positive ion mode. CID mass spectra obtained from molecular ions facilitate the characterization of both the type and substitution pattern of such compounds. Therefore, LC/ESI‐MS/MS represents a valuable tool for comprehensive qualitative and quantitative analysis of this compound class. Copyright © 2008 John Wiley &amp; Sons, Ltd.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1607
TI  - Putrescine N-methyltransferase – The start for alkaloids
JO  - Phytochemistry
PY  - 2009
SP  - 1708-1718
AU  - Biastoff, S.
AU  - Brandt, W.
AU  - Dräger, B.
AU  - 
VL  - 70
UR  - 
DO  - 10.1016/j.phytochem.2009.06.012
AB  - Putrescine N-methyltransferase (PMT) catalyses S-adenosylmethionine (SAM) dependent methylation of the diamine putrescine. The product N-methylputrescine is the first specific metabolite on the route to nicotine, tropane, and nortropane alkaloids. PMT cDNA sequences were cloned from tobacco species and other Solanaceae, also from nortropane-forming Convolvulaceae and enzyme proteins were synthesised in Escherichia coli. PMT activity was measured by HPLC separation of polyamine derivatives and by an enzyme-coupled colorimetric assay using S-adenosylhomocysteine. PMT cDNA sequences resemble those of plant spermidine synthases (putrescine aminopropyltransferases) and display little similarity to other plant methyltransferases. PMT is likely to have evolved from the ubiquitous enzyme spermidine synthase. PMT and spermidine synthase proteins share the same overall protein structure; they bind the same substrate putrescine and similar co-substrates, SAM and decarboxylated S-adenosylmethionine. The active sites of both proteins, however, were shaped differentially in the course of evolution. Phylogenetic analysis of both enzyme groups from plants revealed a deep bifurcation and confirmed an early descent of PMT from spermidine synthase in the course of angiosperm development.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1606
TI  - Evolution of putrescine N-methyltransferase from spermidine synthase demanded alterations in substrate binding
JO  - FEBS Lett.
PY  - 2009
SP  - 3367-3374
AU  - Biastoff, S.
AU  - Reinhardt, N.
AU  - Reva, V.
AU  - Brandt, W.
AU  - Dräger, B.
AU  - 
VL  - 583
UR  - 
DO  - 10.1016/j.febslet.2009.09.043
AB  - Putrescine N ‐methyltransferase (PMT) catalyses S ‐adenosylmethionine (SAM)‐dependent methylation of putrescine in tropane alkaloid biosynthesis. PMT presumably evolved from the ubiquitous spermidine synthase (SPDS). SPDS protein structure suggested that only few amino acid exchanges in the active site were necessary to achieve PMT activity. Protein modelling, mutagenesis, and chimeric protein construction were applied to trace back evolution of PMT activity from SPDS. Ten amino acid exchanges in Datura stramonium  SPDS dismissed the hypothesis of facile generation of PMT activity in existing SPDS proteins. Chimeric PMT and SPDS enzymes were active and indicated the necessity for a different putrescine binding site when PMT developed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1669
TI  - Multiple Multicomponent Macrocyclizations (MiBs): A Strategic Development Toward Macrocycle Diversity
JO  - Chem. Rev.
PY  - 2009
SP  - 796-814
AU  - Wessjohann, L. A.
AU  - Rivera, D. G.
AU  - Vercillo, O. E.
AU  - 
VL  - 109
UR  - 
DO  - 10.1021/cr8003407
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1668
TI  - Enzymatic C–C-Coupling Prenylation: Bioinformatics – Modelling – Mechanism – Protein-Redesign – Biocatalytic Application
JO  - Chimia
PY  - 2009
SP  - 340-344
AU  - Wessjohann, L.
AU  - Zakharova, S.
AU  - Schulze, D.
AU  - Kufka, J.
AU  - Weber, R.
AU  - Bräuer, L.
AU  - Brandt, W.
AU  - 
VL  - 63
UR  - 
DO  - 10.2533/chimia.2009.340
AB  - The functional role of isoprenoids and especially enzymatic prenylation in nature and human application is briefly covered, with the focus on bioinformatical, mechanistical and structural aspects of prenyltransferases and terpene synthases. These enzymes are as yet underrepresented but perspectively useful biocatalysts for C–C couplings of aromatic and isoprenoid substrates. Some examples of the successful use in chemoenzymatic synthesis are given including an application for the otherwise difficult synthesis of Kuhistanol A. Computational structure-based site-directed mutagenesis can be used for rational enzyme redesign to obtain altered substrate and product specificities, which is demonstrated for terpene cyclases.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1659
TI  - Sinapoyltransferases in the light of molecular evolution
JO  - Phytochemistry
PY  - 2009
SP  - 1652-1662
AU  - Stehle, F.
AU  - Brandt, W.
AU  - Stubbs, M. T.
AU  - Milkowski, C.
AU  - Strack, D.
AU  - 
VL  - 70
UR  - 
DO  - 10.1016/j.phytochem.2009.07.023
AB  - Acylation is a prevalent chemical modification that to a significant extent accounts for the tremendous diversity of plant metabolites. To catalyze acyl transfer reactions, higher plants have evolved acyltransferases that accept β-acetal esters, typically 1-O-glucose esters, as an alternative to the ubiquitously occurring CoA-thioester-dependent enzymes. Shared homology indicates that the β-acetal ester-dependent acyltransferases are derived from a common hydrolytic ancestor of the Serine CarboxyPeptidase (SCP) type, giving rise to the name Serine CarboxyPeptidase-Like (SCPL) acyltransferases. We have analyzed structure–function relationships, reaction mechanism and sequence evolution of Arabidopsis 1-O-sinapoyl-β-glucose:l-malate sinapoyltransferase (AtSMT) and related enzymes to investigate molecular changes required to impart acyltransferase activity to hydrolytic enzymes. AtSMT has maintained the catalytic triad of the hydrolytic ancestor as well as part of the H-bond network for substrate recognition to bind the acyl acceptor l-malate. A Glu/Asp substitution at the amino acid position preceding the catalytic Ser supports binding of the acyl donor 1-O-sinapoyl-β-glucose and was found highly conserved among SCPL acyltransferases. The AtSMT-catalyzed acyl transfer reaction follows a random sequential bi-bi mechanism that requires both substrates 1-O-sinapoyl-β-glucose and l-malate bound in an enzyme donor–acceptor complex to initiate acyl transfer. Together with the strong fixation of the acyl acceptor l-malate, the acquisition of this reaction mechanism favours transacylation over hydrolysis in AtSMT catalysis. The model structure and enzymatic side activities reveal that the AtSMT-mediated acyl transfer proceeds via a short-lived acyl enzyme complex. With regard to evolution, the SCPL acyltransferase clade most likely represents a recent development. The encoding genes are organized in a tandem-arranged cluster with partly overlapping functions. With other enzymes encoded by the respective gene cluster on Arabidopsis chromosome 2, AtSMT shares the enzymatic side activity to disproportionate 1-O-sinapoyl-β-glucoses to produce 1,2-di-O-sinapoyl-β-glucose. In the absence of the acyl acceptor l-malate, a residual esterase activity became obvious as a remnant of the hydrolytic ancestor. With regard to the evolution of Arabidopsis SCPL acyltransferases, our results suggest early neofunctionalization of the hydrolytic ancestor toward acyltransferase activity and acyl donor specificity for 1-O-sinapoyl-β-glucose followed by subfunctionalization to recognize different acyl acceptors.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1658
TI  - Multicomponent reactions for the synthesis of multifunctional agents with activity against cancer cells
JO  - Chem. Commun.
PY  - 2009
SP  - 4702
AU  - Shabaan, S.
AU  - Ba, L. A.
AU  - Abbas, M.
AU  - Burkholz, T.
AU  - Denkert, A.
AU  - Gohr, A.
AU  - Wessjohann, L. A.
AU  - Sasse, F.
AU  - Weber, W.
AU  - Jacob, C.
AU  - 
VL  - 
UR  - 
DO  - 10.1039/B823149D
AB  - Multicomponent Passerini and Ugi reactions enable the fast and efficient synthesis of redox-active multifunctional selenium and tellurium compounds, of which some show considerable cytotoxicity against specific cancer cells.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1654
TI  - Architectural Chemistry: Synthesis of Topologically Diverse Macromulticycles by Sequential Multiple Multicomponent Macrocyclizations
JO  - J. Am. Chem. Soc.
PY  - 2009
SP  - 3721-3732
AU  - Rivera, D. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 131
UR  - 
DO  - 10.1021/ja809005k
AB  - How can conformationally restricted polyvalent molecules be accessed rapidly? A sequential approach involving two multiple multicomponent macrocyclizations including bifunctional building blocks (MiBs) with up to five Ugi-four-component reactions (Ugi-4CR) has been developed to produce nonsymmetric macromulticycles. Topologically diverse structures, such as nonsymmetric cryptands and clam- and igloo-shaped macromulticycles were obtained in reaction sequences that comprise the incorporation of up to 13 building blocks by forming 20 new bonds without purification of intermediates. Cryptands were produced by a sequential-MiB procedure in which the Ugi-type functional groups of the second MiB are attached to the peptoid backbones from the first multicomponent macrocyclization. These macrobicycles show two completely new features; i.e., three different tether chains can be obtained in one pot, and tertiary amide bonds are used as bridgeheads. Alternatively, the same reaction sequence, i.e., MiB/deprotection/MiB, can be used to produce clam-shaped macrobicycles, demonstrated with a tetrafunctional cholanic steroid as a hinge moiety. Macrotetracycles endowed with igloo-type topologies are accessible by an advanced protocol featuring consecutive double and 3-fold Ugi-4CR-based macrocyclizations. Other building blocks than cholanic steroids employed include aryl, heterocyclic, polyether, and other recognition motifs. The examples given are a first-generation demonstration of an “architectural chemistry” that allows to construct three-dimensional multimotif covalent molecular “buildings” of unprecedented complexity by design.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1653
TI  - Rapid Access to N-Substituted Diketopiperazines by One-Pot Ugi-4CR/Deprotection+Activation/Cyclization (UDAC)
JO  - J. Comb. Chem.
PY  - 2009
SP  - 1078-1082
AU  - Rhoden, C. R. B.
AU  - Rivera, D. G.
AU  - Kreye, O.
AU  - Bauer, A. K.
AU  - Westermann, B.
AU  - Wessjohann, L. A.
AU  - 
VL  - 11
UR  - 
DO  - 10.1021/cc900106u
AB  - The most efficient diversity generating approaches to heterocycles are combinations of a multicomponent (MCR) with a cyclization reaction, for example, by Ugi-deprotection-cylization (UDC) protocols. If the desired post-Ugi reaction requires more than one deprotection, for example of two initially protected Ugi-reactive groups, or if it requires additional activation, for example, by an Ugi-activation-cyclization (UAC), either the isolation of intermediates or a sequential process or both become necessary. A recently introduced convertible isonitrile reagent allows a mild and chemoselective in situ post-Ugi activation of the isonitrile-born carboxylate with simultaneous deprotection of the nucleophilic amine, that is, liberation and activation of two Ugi-reactive groups, if desired also under subsequent lactam formation. This is exemplified by the synthesis of peptide-peptoid diketopiperazines.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1651
TI  - Functional characterization of a novel benzylisoquinoline O-methyltransferase suggests its involvement in papaverine biosynthesis in opium poppy (Papaver somniferum L)
JO  - Plant J.
PY  - 2009
SP  - 56-67
AU  - Pienkny, S.
AU  - Brandt, W.
AU  - Schmidt, J.
AU  - Kramell, R.
AU  - Ziegler, J.
AU  - 
VL  - 60
UR  - 
DO  - 10.1111/j.1365-313X.2009.03937.x
AB  - The benzylisoquinoline alkaloids are a highly diverse group of about 2500 compounds which accumulate in a species‐specific manner. Despite the numerous compounds which could be identified, the biosynthetic pathways and the participating enzymes or cDNAs could be characterized only for a few selected members, whereas the biosynthesis of the majority of the compounds is still largely unknown. In an attempt to characterize additional biosynthetic steps at the molecular level, integration of alkaloid and transcript profiling across Papaver  species was performed. This analysis showed high expression of an expressed sequence tag (EST) of unknown function only in Papaver somniferum  varieties. After full‐length cloning of the open reading frame and sequence analysis, this EST could be classified as a member of the class II type O ‐methyltransferase protein family. It was related to O ‐methyltransferases from benzylisoquinoline biosynthesis, and the amino acid sequence showed 68% identical residues to norcoclaurine 6‐O ‐methyltransferase. However, rather than methylating norcoclaurine, the recombinant protein methylated norreticuline at position seven with a K m of 44 μm  using S ‐adenosyl‐l ‐methionine as a cofactor. Of all substrates tested, only norreticuline was converted. Even minor changes in the benzylisoquinoline backbone were not tolerated by the enzyme. Accordingly, the enzyme was named norreticuline 7–O ‐methyltransferase (N7OMT). This enzyme represents a novel O ‐methyltransferase in benzylisoquinoline metabolism. Expression analysis showed slightly increased expression of N7OMT in P. somniferum  varieties containing papaverine, suggesting its involvement in the partially unknown biosynthesis of this pharmaceutically important compound.
A2  - 
C1  - Bioorganic Chemistry; Molecular Signal Processing
ER  - 


TY  - JOUR
ID  - 1649
TI  - First Total Synthesis of Tubulysin B
JO  - Org. Lett.
PY  - 2009
SP  - 5567-5569
AU  - Pando, O.
AU  - Dörner, S.
AU  - Preusentanz, R.
AU  - Denkert, A.
AU  - Porzel, A.
AU  - Richter, W.
AU  - Wessjohann, L.
AU  - 
VL  - 11
UR  - 
DO  - 10.1021/ol902320w
AB  - The first total synthesis of tubulysin B is described. The aziridine route to tubuphenylalanine (Tup) of the tubulysin D/U-series could not be transferred to the synthesis of tubutyrosine (blue moiety). Therefore, tubutyrosine (Tut) was synthesized by a Wittig olefination/diastereoselective catalytic reduction sequence. Interestingly, the C-2 epimer of tubulysin B has a cytotoxic activity almost identical to the natural diastereomer.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1646
TI  - Profiling of Phytosterols, Tocopherols and Tocotrienols in Selected Seed Oils from Botswana by GC–MS and HPLC
JO  - J. Am. Oil. Chem. Soc.
PY  - 2009
SP  - 617-625
AU  - Mitei, Y. C.
AU  - Ngila, J. C.
AU  - Yeboah, S. O.
AU  - Wessjohann, L.
AU  - Schmidt, J.
AU  - 
VL  - 86
UR  - 
DO  - 10.1007/s11746-009-1384-5
AB  - The phytosterol, tocopherol, and tocotrienol profiles for mkukubuyo, Sterculia africana,  manketti, Ricinodendron rautanenni,  mokolwane, Hyphaene petersiana,  morama, Tylosema esculentum,  and moretologa‐kgomo, Ximenia caffra,  seed oils from Botswana have been determined. Normal‐phase HPLC analysis of the unsaponifiable matter showed that among the selected oils, the most abundant tocopherol and tocotrienol were γ‐tocopherol (2232.99 μg/g) and γ‐tocotrienol (246.19 μg/g), detected in manketti and mkukubuyo, respectively. Mokolwane oil, however, contained the largest total tocotrienol (258.47 μg/g). Total tocol contents found in manketti, mokolwane, mkukubuyo, morama, and moretologa‐kgomo oils were 2238.60, 262.40, 246.20, 199.10, and 128.0 μg/g, respectively. GC–MS determination of the relative percentage composition of phytosterols showed 4‐desmethylsterols as the most abundant phytosterols in the oils, by occurring up to 90% in moretologa‐kgomo, mkukubuyo, and manketti seed oils, with β‐sitosterol being the most abundant. Mokolwane seed oil contained the largest percentage composition of 4,4‐dimethylsterols (45.93%). Besides 4‐desmethylsterols (75%), morama oil also contained significant amounts of 4,4‐dimethylsterols and 4‐monomethylsterols (15.72% total). GC–MS determination of the absolute amounts of 4‐desmethylsterols, after SPE fractionation of the unsaponifiable matter, confirmed that β‐sitosterol was the most abundant phytosterol in the test seed oils, with manketti seed oil being the richest source (1326.74 μg/g). The analysis showed total 4‐desmethylsterols content as 1617.41, 1291.88, 861.47, 149.15, and 109.11 μg/g for manketti, mokolwane, mkukubuyo, morama, and moretologa‐kgomo seed oils, respectively.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1645
TI  - Exploring synthetic avenues for the effective synthesis of selenium- and tellurium-containing multifunctional redox agents
JO  - Org. Biomol. Chem.
PY  - 2009
SP  - 4753
AU  - Mecklenburg, S.
AU  - Shaaban, S.
AU  - Ba, L. A.
AU  - Burkholz, T.
AU  - Schneider, T.
AU  - Diesel, B.
AU  - Kiemer, A. K.
AU  - Röseler, A.
AU  - Becker, K.
AU  - Reichrath, J.
AU  - Stark, A.
AU  - Tilgen, W.
AU  - Abbas, M.
AU  - Wessjohann, L. A.
AU  - Sasse, F.
AU  - Jacob, C.
AU  - 
VL  - 7
UR  - 
DO  - 10.1039/B907831B
AB  - Various human illnesses, including several types of cancer and infectious diseases, are related to changes in the cellular redox homeostasis. During the last decade, several approaches have been explored which employ such disturbed redox balances for the benefit of therapy. Compounds able to modulate the intracellular redox state of cells have been developed, which effectively, yet also selectively, appear to kill cancer cells and a range of pathogenic microorganisms. Among the various agents employed, certain redox catalysts have shown considerable promise since they are non-toxic on their own yet develop an effective, often selective cytotoxicity in the presence of the ‘correct’ intracellular redox partners. Aminoalkylation, amide coupling and multicomponent reactions are suitable synthetic methods to generate a vast number of such multifunctional catalysts, which are chemically diverse and, depending on their structure, exhibit various interesting biological activities.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1644
TI  - New Pyridine Alkaloids from Rove Beetles of the Genus Stenus (Coleoptera: Staphylinidae)
JO  - Z. Naturforsch. C
PY  - 2009
SP  - 271-278
AU  - Lusebrink, I.
AU  - Dettner, K.
AU  - Schierling, A.
AU  - Müller, T.
AU  - Daolio, C.
AU  - Schneider, B.
AU  - Schmidt, J.
AU  - Seifert, K.
AU  - 
VL  - 64
UR  - 
DO  - 10.1515/znc-2009-3-420
AB  - Three new pyridine alkaloids were detected in the pygidial glands of some Stenus species. The chemotaxonomic significance of the occurrence of these alkaloids and stenusine in different Stenus species is discussed. The antimicrobial properties of (Z)- and (E)-3-(2- methyl-1-butenyl)-pyridine and the deterrent activities of stenusine and norstenusine were investigated.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1642
TI  - Targeted metabolite and transcript profiling for elucidating enzyme function: isolation of novel N-methyltransferases from three benzylisoquinoline alkaloid-producing species
JO  - Plant J.
PY  - 2009
SP  - 729-743
AU  - Liscombe, D. K.
AU  - Ziegler, J.
AU  - Schmidt, J.
AU  - Ammer, C.
AU  - Facchini, P. J.
AU  - 
VL  - 60
UR  - 
DO  - 10.1111/j.1365-313X.2009.03980.x
AB  - An integrated approach using targeted metabolite profiles and modest EST libraries each containing approximately 3500 unigenes was developed in order to discover and functionally characterize novel genes involved in plant‐specialized metabolism. EST databases have been established for benzylisoquinoline alkaloid‐producing cell cultures of Eschscholzia californica , Papaver bracteatum  and Thalictrum flavum , and are a rich repository of alkaloid biosynthetic genes. ESI‐FTICR‐MS and ESI‐MS/MS analyses facilitated unambiguous identification and relative quantification of the alkaloids in each system. Manual integration of known and candidate biosynthetic genes in each EST library with benzylisoquinoline alkaloid biosynthetic networks assembled from empirical metabolite profiles allowed identification and functional characterization of four N‐ methyltransferases (NMTs). One cDNA from T. flavum  encoded pavine N‐ methyltransferase (TfPavNMT), which showed a unique preference for (±)‐pavine and represents the first isolated enzyme involved in the pavine alkaloid branch pathway. Correlation of the occurrence of specific alkaloids, the complement of ESTs encoding known benzylisoquinoline alkaloid biosynthetic genes and the differential substrate range of characterized NMTs demonstrated the feasibility of bilaterally predicting enzyme function and species‐dependent specialized metabolite profiles.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1639
TI  - Anti-fungal flavonoids from Tibouchina grandifolia
JO  - Biochem. Syst. Ecol.
PY  - 2009
SP  - 63-65
AU  - Kuster, R. M.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 37
UR  - 
DO  - 10.1016/j.bse.2009.01.005
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1638
TI  - Oxidation of the Dihydrochalcone Aspalathin Leads to Dimerization
JO  - J. Agr. Food Chem.
PY  - 2009
SP  - 6838-6843
AU  - Krafczyk, N.
AU  - Heinrich, T.
AU  - Porzel, A.
AU  - Glomb, M. A.
AU  - 
VL  - 57
UR  - 
DO  - 10.1021/jf901614y
AB  - Aspalathin and nothofagin are typical ingredients of unfermented rooibos (Krafczyk, N.; Glomb, M. A. J. Agric. Food Chem.2008, 56, 3368). During oxidation these dihydrochalcones were degraded to higher molecular weight browning products under aerated and nonenzymatic conditions. In the early stages of browning reactions aspalathin formed two dimers. These two compounds were unequivocally established as atropisomers stemming from oxidative A to B ring coupling. Multilayer countercurrent chromatography (MLCCC) and preparative high-performance liquid chromatography (HPLC) were applied to obtain pure substances. The purity and identity of isolated dimers were confirmed by different NMR experiments, HPLC-DAD-MS, and HR-MS. In parallel to the formation of chromophores during the fermentation of black tea, the formation of aspalathin dimers implies an important mechanistic channel for the generation of color during the processing of rooibos.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1637
TI  - Expression, regulation and function of the ISGylation system in prostate cancer
JO  - Oncogene
PY  - 2009
SP  - 2606-2620
AU  - Kiessling, A.
AU  - Hogrefe, C.
AU  - Erb, S.
AU  - Bobach, C.
AU  - Fuessel, S.
AU  - Wessjohann, L.
AU  - Seliger, B.
AU  - 
VL  - 28
UR  - 
DO  - 10.1038/onc.2009.115
AB  - The androgen receptor (AR) plays a crucial role in the modulation of prostate cell proliferation and is involved in the development and progression of prostate cancer (PCa). An understanding of the complex regulation of AR provides novel treatment options for PCa. Here, we show (i) that the ubiquitin-like modifier, interferon-stimulated gene 15 (ISG15), and most enzymes involved in ISG15 conjugation were upregulated in tumor samples versus in non-malignant tissues of PCa patients and (ii) that the expression of these components significantly differed between tumors in patients treated with and without androgen ablation. Using PCa cell lines as in vitro models, the specific androgen-mediated, AR-dependent regulation of the ISGylation components was confirmed. In addition, the ISGylation system controls AR mRNA and protein expressions, as overexpression of Ube1L as a limiting ISGylation factor in the AR+ androgen-sensitive PCa cell line, LNCaP, results in significant AR upregulation, accompanied by an increased proliferation even under androgen deprivation. Accordingly, Ube1L knockdown decreased the AR expression. Thus, this study describes for the first time the modulation of AR expression by ISGylation components, which affects the proliferation of PCa cells, thereby providing evidence for a novel function of the ISGylation system in malignant transformation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1672
TI  - Removal of Substrate Inhibition and Increase in Maximal Velocity in the Short Chain Dehydrogenase/Reductase Salutaridine Reductase Involved in Morphine Biosynthesis
JO  - J. Biol. Chem.
PY  - 2009
SP  - 26758-26767
AU  - Ziegler, J.
AU  - Brandt, W.
AU  - Geißler, R.
AU  - Facchini, P. J.
AU  - 
VL  - 284
UR  - 
DO  - 10.1074/jbc.M109.030957
AB  - Salutaridine reductase (SalR, EC 1.1.1.248) catalyzes the stereospecific reduction of salutaridine to 7(S)-salutaridinol in the biosynthesis of morphine. It belongs to a new, plant-specific class of short-chain dehydrogenases, which are characterized by their monomeric nature and increased length compared with related enzymes. Homology modeling and substrate docking suggested that additional amino acids form a novel α-helical element, which is involved in substrate binding. Site-directed mutagenesis and subsequent studies on enzyme kinetics revealed the importance of three residues in this element for substrate binding. Further replacement of eight additional residues led to the characterization of the entire substrate binding pocket. In addition, a specific role in salutaridine binding by either hydrogen bond formation or hydrophobic interactions was assigned to each amino acid. Substrate docking also revealed an alternative mode for salutaridine binding, which could explain the strong substrate inhibition of SalR. An alternate arrangement of salutaridine in the enzyme was corroborated by the effect of various amino acid substitutions on substrate inhibition. In most cases, the complete removal of substrate inhibition was accompanied by a substantial loss in enzyme activity. However, some mutations greatly reduced substrate inhibition while maintaining or even increasing the maximal velocity. Based on these results, a double mutant of SalR was created that exhibited the complete absence of substrate inhibition and higher activity compared with wild-type SalR.
A2  - 
C1  - Bioorganic Chemistry; Molecular Signal Processing
ER  - 


TY  - JOUR
ID  - 1671
TI  - Evolution of morphine biosynthesis in opium poppy
JO  - Phytochemistry
PY  - 2009
SP  - 1696-1707
AU  - Ziegler, J.
AU  - Facchini, P. J.
AU  - Geißler, R.
AU  - Schmidt, J.
AU  - Ammer, C.
AU  - Kramell, R.
AU  - Voigtländer, S.
AU  - Gesell, A.
AU  - Pienkny, S.
AU  - Brandt, W.
AU  - 
VL  - 70
UR  - 
DO  - 10.1016/j.phytochem.2009.07.006
AB  - Benzylisoquinoline alkaloids (BIAs) are a group of nitrogen-containing plant secondary metabolites comprised of an estimated 2500 identified structures. In BIA metabolism, (S)-reticuline is a key branch-point intermediate that can be directed into several alkaloid subtypes with different structural skeleton configurations. The morphinan alkaloids are one subclass of BIAs produced in only a few plant species, most notably and abundantly in the opium poppy (Papaver somniferum). Comparative transcriptome analysis of opium poppy and several other Papaver species that do not accumulate morphinan alkaloids showed that known genes encoding BIA biosynthetic enzymes are expressed at higher levels in P. somniferum. Three unknown cDNAs that are co-ordinately expressed with several BIA biosynthetic genes were identified as enzymes in the pathway. One of these enzymes, salutaridine reductase (SalR), which is specific for the production of morphinan alkaloids, was isolated and heterologously overexpressed in its active form not only from P. somniferum, but also from Papaver species that do not produce morphinan alkaloids. SalR is a member of a class of short chain dehydrogenase/reductases (SDRs) that are active as monomers and possess an extended amino acid sequence compared with classical SDRs. Homology modelling and substrate docking revealed the substrate binding site for SalR. The amino acids residues conferring salutaridine binding were compared to several members of the SDR family from different plant species, which non-specifically reduce (−)-menthone to (+)-neomenthol. Previously, it was shown that some of these proteins are involved in plant defence. The recruitment of specific monomeric SDRs from monomeric SDRs involved in plant defence is discussed.
A2  - 
C1  - Bioorganic Chemistry; Molecular Signal Processing
ER  - 


TY  - CHAP
ID  - 106
TI  - Terpenoids from Curcuma species
T2  - Proceedings of the Workshop on Medinical Plants of Bangladesh
PB  - 
PY  - 2009
SP  - 
AU  - Khine, M. M.
AU  - Arnold, N.
AU  - Franke, K.
AU  - Wessjohann, L. A.
AU  - 
VL  - 
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 105
TI  - Phytochemical Constituents of Selected Vitis Species
T2  - Proceedings of the Workshop on Medinical Plants of Bangladesh
PB  - 
PY  - 2009
SP  - 
AU  - Khine, M. M.
AU  - Franke, K.
AU  - Arnold, N.
AU  - Wessjohann, L. A.
AU  - 
VL  - 
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1758
TI  - Non-substrate peptides influencing dipeptidyl peptidase IV/CD26 activity and immune cell function
JO  - Front. Biosci.
PY  - 2008
SP  - 3194
AU  - Wrenger, S.
AU  - Faust, J.
AU  - Mrestani-Klaus, C.
AU  - Brandt, W.
AU  - Thielitz, A.
AU  - Neubert, K.
AU  - Reinhold, D.
AU  - 
VL  - Volume
UR  - 
DO  - 10.2741/2920
AB  - Investigations using inhibitors of dipeptidyl peptidase IV (DP IV) activities and DP IV-/- mice indicated an immunoregulatory role of DP IV that could not be compensated by DP IV-like enzymes. The HIV-1 Tat protein was identified as the first natural inhibitor of DP IV and as immunosuppressor. This review summarizes our investigations on the identification of the amino acid motif of Tat responsible for DP IV inhibition and of endogenous DP IV-inhibitory ligands that suppress immune cell activation. Examinations on numerous peptides carrying the N-terminal Xaa-Xaa-Pro motif of Tat revealed that tryptophan at position two strongly enhanced DP IV inhibition and immunosuppression. Here, we present evidence that the thromboxane A2 receptor exposing N-terminal Met-Trp-Pro at the cell surface could be a potential endogenous, inhibitory DP IV ligand. Moreover, our data suggest that the major envelope proteins p37k of the orhtopoxviruses variola virus and vaccinia virus, as well as the B2L antigen of the parapoxvirus orf, that also carry N-terminal Met-Trp-Pro, could mediate immunosuppressive effects. Further examinations are in progress to identify new physiologic, inhibitory DP IV ligands and to enlighten the mechanism underlying the DP IV-mediated effects.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1756
TI  - Synthesis of Selenocysteine and Its Derivatives with an Emphasis on Selenenylsulfide (-Se-S-) Formation
JO  - Chem. Biodivers.
PY  - 2008
SP  - 375-388
AU  - Wessjohann, L.
AU  - Schneider, A.
AU  - 
VL  - 5
UR  - 
DO  - 10.1002/cbdv.200890038
AB  - A short survey of historic and current methods for the synthesis of selenocysteine, selenocystine, and derivatives and related compounds is presented, with an additional emphasis on the formation of selenocysteine‐derived SeS bridges. The majority of methods to the amino acid starts with protected and O ‐activated serine, but also other concepts are included such as radical or multicomponent strategies, the latter allowing also direct access to peptoids in one pot. Of special importance is the monomeric oxidative cyclization of selenocysteine–cysteine peptides to eight‐membered and larger rings with a selenenylsulfide bridge, a crucial element in several selenoproteins.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1755
TI  - Reaction of secondary and tertiary aliphatic halides with aromatic aldehydes mediated by chromium(II): a selective cross-coupling of alkyl and ketyl radicals
JO  - Tetrahedron
PY  - 2008
SP  - 2134-2142
AU  - Wessjohann, L. A.
AU  - Schmidt, G.
AU  - Schrekker, H. S.
AU  - 
VL  - 64
UR  - 
DO  - 10.1016/j.tet.2007.12.039
AB  - Takai–Utimoto reactions with secondary and tertiary aliphatic halides usually failed according to previous reports. Now, significant improvements could be achieved, and especially secondary aliphatic halides can be coupled to aromatic aldehydes in yields of up to &gt;95%. A variety of processes are competing with the desired one, and thus conditions must be adapted to the nature of the aldehyde as well as the aliphatic halide used, as the outcome of these reactions is strongly affected by the putative radical intermediates.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1754
TI  - Amino Alcohols in Organocatalysed Acylation and Deacylation: The Effect of Dialkylamino Substituents on the Rate
JO  - Adv. Synth. Catal.
PY  - 2008
SP  - 107-112
AU  - Wessjohann, L.
AU  - Zhu, M.
AU  - 
VL  - 350
UR  - 
DO  - 10.1002/adsc.200600491
AB  - In alcohols and esters, a neighbouring dialkylamino group can enhance the reactivity towards acylation and deacylation, respectively, that is, such amino alcohols can act as transacylation catalysts like DMAP. This effect is dependent on the number of (carbon) spacer atoms, flexibility of the molecule and the presence and position of further heteroatoms. Based on this effect, the site selective acylation and deacylation of desmycosin, a macrocycle antibiotic possessing an amino sugar moiety, is described.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1749
TI  - Design and Synthesis of Cyclic RGD Pentapeptoids by Consecutive Ugi Reactions
JO  - Org. Lett.
PY  - 2008
SP  - 205-208
AU  - Vercillo, O. E.
AU  - Andrade, C. K. Z.
AU  - Wessjohann, L. A.
AU  - 
VL  - 10
UR  - 
DO  - 10.1021/ol702521g
AB  - A new strategy for the synthesis of cyclic peptoids was developed. The approach is based on the use of consecutive Ugi reactions for the assembly of the acyclic peptoid and for the ring closure. Cyclopentapeptoid analogues of the RGD peptides were designed and synthesized using this methodology. The results confirm the versatility and efficiency of the method for the preparation of cyclic oligopeptoids.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1745
TI  - Determination of β‐carboline alkaloids in fruiting bodies of Hygrophorus spp. by liquid chromatography/electrospray ionisation tandem mass spectrometry
JO  - Phytochem. Anal.
PY  - 2008
SP  - 335-341
AU  - Teichert, A.
AU  - Lübken, T.
AU  - Schmidt, J.
AU  - Kuhnt, C.
AU  - Huth, M.
AU  - Porzel, A.
AU  - Wessjohann, L.
AU  - Arnold, N.
AU  - 
VL  - 19
UR  - 
DO  - 10.1002/pca.1057
AB  - The β ‐carboline alkaloids harmane (1 ) and norharmane (2 ) were isolated from fruiting bodies of Hygrophorus eburneus  (Bull.) Fr. as well as brunnein A (3 ) from Hygrophorus hyacinthinus  Quél. (Tricholomataceae, Agaricales) for the first time. Their occurrence within the genus was investigated using liquid chromatography/electrospray ionisation tandem mass spectrometric methods, especially by selected reaction monitoring. Based on these results their chemotaxonomical relevance is discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1744
TI  - N-Glucosyl-1H-indole Derivatives from Cortinarius brunneus (Basidiomycetes)
JO  - Chem. Biodivers.
PY  - 2008
SP  - 664-669
AU  - Teichert, A.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 5
UR  - 
DO  - 10.1002/cbdv.200890062
AB  - Two new N ‐glucosylated indole alkaloids were isolated from fruiting bodies of the basidiomycete Cortinarius brunneus  (Pers .) Fr . The structures were elucidated by means of the spectroscopic data. Additionally, the very recently reported compounds N‐ 1‐β‐ glucopyranosyl‐3‐(carboxymethyl)‐1H ‐indole (3 ) and N‐ 1‐β‐ glucopyranosyl‐3‐(2‐methoxy‐2‐oxoethyl)‐1H ‐indole (4 ) could be detected. Compound 3  is the N ‐glucoside of the plant‐growth regulator 1H ‐indole‐3‐acetic acid (IAA), but, in contrast, it does not exhibit auxin‐like activity in an Arabidopsis thaliana  tap root elongation assay.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1743
TI  - (Iso)-Quinoline Alkaloids from Fungal Fruiting Bodies of Cortinarius subtortus
JO  - J. Nat. Prod.
PY  - 2008
SP  - 1092-1094
AU  - Teichert, A.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 71
UR  - 
DO  - 10.1021/np8000859
AB  - Chemical analysis of the fruiting bodies of the agaricoid fungus Cortinarius subtortus yielded three new natural products, two quinoline and one isocarbostyryl alkaloid. The structures of compounds 1−3 were determined by analysis of NMR and MS data. Compound 1 exhibited inhibitory effects against the phytopathogenic fungus Colletotrichum coccodes. All three compounds displayed moderate antioxidant activity in a DPPH free radical scavenging bioassay.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1737
TI  - Activities of Arabidopsis sinapoylglucose:malate sinapoyltransferase shed light on functional diversification of serine carboxypeptidase-like acyltransferases
JO  - Phytochemistry
PY  - 2008
SP  - 1826-1831
AU  - Stehle, F.
AU  - Brandt, W.
AU  - Schmidt, J.
AU  - Milkowski, C.
AU  - Strack, D.
AU  - 
VL  - 69
UR  - 
DO  - 10.1016/j.phytochem.2008.03.021
AB  - Analysis of the catalytic properties of the serine carboxypeptidase-like (SCPL) 1-O-sinapoyl-β-glucose:l-malate sinapoyltransferase (SMT) from Arabidopsis showed that the enzyme exhibits besides its primary sinapoylation of l-malate, minor hydrolytic and disproportionation activities, producing free sinapic acid and 1,2-di-O-sinapoyl-β-glucose, respectively. The ability of the enzyme to liberate sinapic acid from the donor molecule 1-O-sinapoyl-β-glucose indicates the existence of a short-lived acylenzyme intermediate in the proposed random sequential bi–bi mechanism of catalysis. SMT-catalyzed formation of disinapoylglucose has been corroborated by docking studies with an established homology structure model that illustrates the possible binding of two 1-O-sinapoyl-β-glucose molecules in the active site and the intermolecular reaction of the two glucose esters. The SMT gene is embedded in a tandem cluster of five SCPL sinapoyltransferase genes, which encode enzymes with high amino acid sequence identities and partially overlapping substrate specificities. We assume that in recent duplications of genes encoding SCPL proteins, neofunctionalization of the duplicates to accept 1-O-sinapoyl-β-glucose as acyl donor was gained first, followed by subfunctionalization leading to different acyl acceptor specificities.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1735
TI  - Benzoxazinoid biosynthesis in dicot plants
JO  - Phytochemistry
PY  - 2008
SP  - 2668-2677
AU  - Schullehner, K.
AU  - Dick, R.
AU  - Vitzthum, F.
AU  - Schwab, W.
AU  - Brandt, W.
AU  - Frey, M.
AU  - Gierl, A.
AU  - 
VL  - 69
UR  - 
DO  - 10.1016/j.phytochem.2008.08.023
AB  - Benzoxazinoids are common defence compounds of the grasses and are sporadically found in single species of two unrelated orders of the dicots. In the three dicotyledonous species Aphelandra squarrosa, Consolida orientalis and Lamium galeobdolon the main benzoxazinoid aglucon is 2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one (DIBOA). While benzoxazinoids in Aphelandra squarrosa are restricted to the root, in Consolida orientalis and Lamium galeobdolon DIBOA is found in all above ground organs of the adult plant in concentrations as high as in the seedling of maize. The initial biosynthetic steps in dicots and monocots seem to be identical. Indole is most probably the first specific intermediate that is oxygenated to indolin-2-one by a cytochrome P450 enzyme. C. orientalis has an active indole-3-glycerolphosphate lyase for indole formation that evolved independently from its orthologous function in maize. The properties and evolution of plant indole-3-glycerolphosphate lyases are discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1732
TI  - Accumulation of apocarotenoids in mycorrhizal roots of leek (Allium porrum)
JO  - Phytochemistry
PY  - 2008
SP  - 1680-1688
AU  - Schliemann, W.
AU  - Kolbe, B.
AU  - Schmidt, J.
AU  - Nimtz, M.
AU  - Wray, V.
AU  - 
VL  - 69
UR  - 
DO  - 10.1016/j.phytochem.2008.02.015
AB  - Colonization of the roots of leek (Allium porrum L.) by the arbuscular mycorrhizal fungus Glomus intraradices induced the formation of apocarotenoids, whose accumulation has been studied over a period of 25 weeks. Whereas the increase in the levels of the dominating cyclohexenone derivatives resembles the enhancement of root length colonization, the content of mycorradicin derivatives remains relatively low throughout. Structural analysis of the cyclohexenone derivatives by mass spectrometry and NMR spectroscopy showed that they are mono- and diglycosides of 13-hydroxyblumenol C and blumenol C acylated with 3-hydroxy-3-methyl-glutaric and/or malonic acid. Along with the isolation of three known compounds five others are shown to be hitherto unknown members of the fast-growing family of mycorrhiza-induced cyclohexenone conjugates.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1728
TI  - Rapid generation of macrocycles with natural-product-like side chains by multiple multicomponent macrocyclizations (MiBs)
JO  - Org. Biomol. Chem.
PY  - 2008
SP  - 1787
AU  - Rivera, D. G.
AU  - Vercillo, O. E.
AU  - Wessjohann, L. A.
AU  - 
VL  - 6
UR  - 
DO  - 10.1039/B715393G
AB  - A small parallel library of peptoid macrocycles with natural-product-derived side chains of biological importance was produced by Ugi-type multiple multicomponent macrocyclizations including bifunctional building blocks (Ugi-MiBs). Diverse exocyclic elements of high relevance in natural recognition processes, i.e., all functional amino acid residues (e.g., Cys, Arg, His, Trp) and even sugar moieties, can be introduced in a one-pot process into different types of peptoid-containing macrocyclic skeletons. This is exemplified by the use of a diamine/diisocyanide combination of Ugi-MiBs and N-protected α-amino acids or carboxy-functionalized carbohydrates as source for the natural-product-like exocyclic elements. Employed as the acid components of the multiple Ugi reactions, they appear as N-amide substituents on the macrocyclic cores. The use of different diamines and diisocyanides allows an easy variation of the N- to C-directionality and therefore of the position of the exocyclic elements.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1727
TI  - A Biomimetic Approach for Polyfunctional Secocholanes: Tuning Flexibility and Functionality on Peptidic and Macrocyclic Scaffolds Derived from Bile Acids
JO  - J. Org. Chem.
PY  - 2008
SP  - 6229-6238
AU  - Rivera, D. G.
AU  - Pando, O.
AU  - Bosch, R.
AU  - Wessjohann, L. A.
AU  - 
VL  - 73
UR  - 
DO  - 10.1021/jo800708m
AB  - Bile acids are important scaffolds in medicinal and supramolecular chemistry. However, the use of seco bile acids, i.e., bile acids with opened rings, as cores or building blocks for the assembly of complex peptide conjugates or macrocycles has remained elusive so far. A biomimetic approach to secocholanes, based on an oxidative ring-expansion/ring-opening sequence, offers efficient access to novel structures with tunable flexibility and functionality. The process preserves selected portions of the original stereochemical and functional information of the steroid, while additional structural elements are incorporated in further (diversity-generating) steps. The potential of these building blocks for peptide and macrocycle chemistry is exemplified by the attachment of relevant α-amino acids and by the production of various complex macrocycles obtained by conventional (e.g., macrolactonization and macrolactamization) and multicomponent (e.g., Ugi four-component) macrocyclizations. This combination of secocholanic skeleton manipulation with, e.g., varied types of macrocyclization protocols, produces high levels of skeletal diversity and complexity. Therefore, this approach may have applicability either for the synthesis of biologically active ligands or as artificial receptors (“hosts”).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1724
TI  - Alkaloids from the Mushroom Pseudobaeospora pyrifera, Pyriferines A−C
JO  - J. Nat. Prod.
PY  - 2008
SP  - 1620-1622
AU  - Quang, D. N.
AU  - Spiteller, P.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Geissler, T.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 71
UR  - 
DO  - 10.1021/np800365f
AB  - Three novel alkaloids (1−3), named pyriferines A−C, were isolated from fruiting bodies of Pseudobaeospora pyrifera. They possess an unusual eight-membered N/O-acetal ring, derived from l-glutamic acid, that is connected to an enolized 1,3-diketo moiety. The structures were determined by spectroscopic methods, and the absolute configuration of the glutamic acid moiety was established using GC-MS after Mosher-type derivatization.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1719
TI  - NMR, GC–MS and ESI-FTICR-MS Profiling of Fatty Acids and Triacylglycerols in Some Botswana Seed Oils
JO  - J. Am. Oil. Chem. Soc.
PY  - 2008
SP  - 1021-1032
AU  - Mitei, Y. C.
AU  - Ngila, J. C.
AU  - Yeboah, S. O.
AU  - Wessjohann, L.
AU  - Schmidt, J.
AU  - 
VL  - 85
UR  - 
DO  - 10.1007/s11746-008-1301-3
AB  - In the search for non‐traditional seed oils, physicochemical parameters, fatty acid (FA) and triacylglycerol (TAG) profiles for five Botswana seed oils, obtained by Soxhlet extraction, were determined. GC–MS and 1H‐NMR analyses showed the FA profiles for mkukubuyo, Sterculia africana , and manketti, Ricinodendron rautanenii , seed oils dominated by linoleic and oleic acids, 26.1, 16.7 and 51.9, 24.4%, respectively, with S. africana  containing significant amounts of cyclic FAs (19.9%). Mokolwane, Hyphaene petersiana , seed oil was typically lauric; 12:0 and 14:0 acids were 25.9 and 13.4%, respectively. Morama, Tylosema esculentum , seed oil resembled olive oil; 18:1 (47.3%) and 18:2 (23.4%) acids dominated. Moretologa‐kgomo, Ximenia caffra , seed oil had 45.8% of 18:1 FA, plus significant amounts of very long chain FAs: 26:1 (5.8%), 28:1 (13.9%), 30:1 (3.9%), and acetylenic acids, 9a‐18:1 (1.5%) and 9a, 11t‐18:2 (16.0%). TAG classes and regiochemistry were determined with ESI‐FTICR‐MS, and 13C‐NMR spectra, respectively. Morama showed seven major TAG classes with C54:4 and C54:3 dominating; mokolwane had 16 major classes with C32:0, C38:0 and C42:2 dominating; manketti had 11 major classes with C54:7, C54:6 and C54:4 dominating; mkukubuyo had 12 major classes with C52:4, C52:3 and C54:4 dominating; moretologa‐kgomo had 30 major TAG classes with C64:5, C64:3 and C62:3 dominating. Saturated FAs were generally distributed over the sn ‐1(3) position for morama, manketti, and moretologa‐kgomo but at the sn ‐2 position for mokolwane and mkukubuyo. These findings indicate that morama and manketti seed oils can be developed for food uses, whilst moretologa‐kgomo and mkukubuyo seed oils only for nonfood uses.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1716
TI  - Multiple Multicomponent Macrocyclizations Including Bifunctional Building Blocks (MiBs) Based on Staudinger and Passerini Three-Component Reactions
JO  - J. Org. Chem.
PY  - 2008
SP  - 1762-1767
AU  - León, F.
AU  - Rivera, D. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 73
UR  - 
DO  - 10.1021/jo7022125
AB  - Multiple multicomponent macrocyclizations including bifunctional buildings blocks (MiBs) so far have relied almost exclusively on Ugi reactions. The efficient expansion to non-Ugi-MiBs is exemplified by the synthesis of tetra-β-lactam and bis-α-acyloxy carboxamide macrocycles based on multiple Staudinger and Passerini three-component reactions (3CR), respectively. A recent variation of the Passerini-3CR that involves primary alcohols, isocyanides, and carboxylic acids under oxidative conditions is successfully adapted to this procedure.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1713
TI  - A lipoxygenase with linoleate diol synthase activity from Nostoc sp. PCC 7120
JO  - Biochem. J.
PY  - 2008
SP  - 347-357
AU  - Lang, I.
AU  - Göbel, C.
AU  - Porzel, A.
AU  - Heilmann, I.
AU  - Feussner, I.
AU  - 
VL  - 410
UR  - 
DO  - 10.1042/BJ20071277
AB  - The dioxygenation of PUFAs (polyunsaturated fatty acids) in plants is mainly catalysed by members of the LOX (lipoxygenase) enzyme family. LOX products may be further metabolized, and are known as signalling substances in plant development and in responses to wounding and pathogen attack. In contrast with the situation in eukaryotes, information on the relevance of lipid peroxide metabolism in prokaryotic organisms is scarce. Therefore, we aimed to analyse LOXs and oxylipin patterns of cyanobacterial origin. A search of the genomic sequence of the cyanobacterium Nostoc sp. PCC 7120 suggested an open reading frame encoding a putative LOX named NspLOX that harboured an N-terminal extension. Individual analysis of recombinant C-terminal domain revealed enzymatic activity as a linoleate (9R)-LOX. Analysis of the full-length NspLOX protein, however, revealed linoleate diol synthase activity, generating (10E,12E)-9,14-dihydroxy-10,12-octadecadienoic acid as the main product from LA (linoleic acid) and (10E,12E,14E)-9,16-dihydroxy-10,12,14-octadecatrienoic acid as the main product from ALA (α-LA) substrates respectively, with ALA as preferred substrate. The enzyme exhibited a broad pH optimum between pH 7 and pH 10. Soluble extracts of Nostoc sp. contain more 9-LOX-derived hydroperoxides in sonified than in non-sonified cells, but products of full-length NspLOX were not detectable under the conditions used. As no other LOX-like sequence was identified in the genome of Nostoc sp. PCC 7120, the results presented suggest that (9R)-LOX-derived oxylipins may represent the endogenous products of NspLOX. Based on the biochemical results of NspLOX, we suggest that this bifunctional enzyme may represent a more ancient way to control the intracellular amount of oxylipins in this cyanobacterium.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1711
TI  - Functional and Structural Characterization of a Cation-dependent O-Methyltransferase from the Cyanobacterium Synechocystis sp. Strain PCC 6803
JO  - J. Biol. Chem.
PY  - 2008
SP  - 20888-20896
AU  - Kopycki, J. G.
AU  - Stubbs, M. T.
AU  - Brandt, W.
AU  - Hagemann, M.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Schliemann, W.
AU  - Zenk, M. H.
AU  - Vogt, T.
AU  - 
VL  - 283
UR  - 
DO  - 10.1074/jbc.M801943200
AB  - The coding sequence of the cyanobacterium Synechocystis sp. strain PCC 6803 slr0095 gene was cloned and functionally expressed in Escherichia coli. The corresponding enzyme was classified as a cation- and S-adenosyl-l-methionine-dependent O-methyltransferase (SynOMT), consistent with considerable amino acid sequence identities to eukaryotic O-methyltransferases (OMTs). The substrate specificity of SynOMT was similar with those of plant and mammalian CCoAOMT-like proteins accepting a variety of hydroxycinnamic acids and flavonoids as substrates. In contrast to the known mammalian and plant enzymes, which exclusively methylate the meta-hydroxyl position of aromatic di- and trihydroxy systems, Syn-OMT also methylates the para-position of hydroxycinnamic acids like 5-hydroxyferulic and 3,4,5-trihydroxycinnamic acid, resulting in the formation of novel compounds. The x-ray structure of SynOMT indicates that the active site allows for two alternative orientations of the hydroxylated substrates in comparison to the active sites of animal and plant enzymes, consistent with the observed preferred para-methylation and position promiscuity. Lys3 close to the N terminus of the recombinant protein appears to play a key role in the activity of the enzyme. The possible implications of these results with respect to modifications of precursors of polymers like lignin are discussed.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1709
TI  - Fast access to total energies
JO  - Chem. Cent. J.
PY  - 2008
SP  - P35
AU  - Klein, R.
AU  - Brandt, W.
AU  - 
VL  - 2
UR  - 
DO  - 10.1186/1752-153X-2-S1-P35
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1707
TI  - Platinum(IV) Metallacrown Ethers: Synthesis, Structures, Host Properties and Anticancer Evaluation
JO  - Organometallics
PY  - 2008
SP  - 4917-4927
AU  - Kelly, M. E.
AU  - Dietrich, A.
AU  - Gómez-Ruiz, S.
AU  - Kalinowski, B.
AU  - Kaluderović, G. N.
AU  - Müller, T.
AU  - Paschke, R.
AU  - Schmidt, J.
AU  - Steinborn, D.
AU  - Wagner, C.
AU  - Schmidt, H.
AU  - 
VL  - 27
UR  - 
DO  - 10.1021/om800323z
AB  - Platinum(IV) metallacrown ethers [PtBr2Me2{im(CH2CH2O)xCH2CH2im}] (im = imidazol-1-yl; x = 2−5, 7; 3−7) and [PtBr2Me2{bim(CH2CH2O)xCH2CH2bim}] (bim = benzimidazol-1-yl; x = 1, 2, 5, 7; 9−12) were synthesized via the reaction of [(PtBr2Me2)n] with the appropriate α,ω-bis(imidazol-1-yl) or α,ω-bis(benzimidazol-1-yl) polyether. Reactions with 1,2-bis(imidazol-1-yl)ethane, bis(2-(imidazol-1-yl)ethyl) ether, or 1,2-bis(benzimidazol-1-yl)ethane yielded the dinuclear complexes [(PtBr2Me2)2{μ-im(CH2CH2O)xCH2CH2im}2] (x = 0, 1; 1, 2) and [(PtBr2Me2)2{μ-bimCH2CH2bim}2] (8), respectively. In addition, the diiodo complex [PtI2Me2{im(CH2CH2O)2CH2CH2im}] (13) was prepared from the reaction of [PtMe2(cod)] with I2 in the presence of im(CH2CH2O)2CH2CH2im. Characterization by microanalysis and NMR spectroscopy, as well as X-ray crystal structure analysis of several of the metallacrown ethers (3, 5, 9 and 10) and dinuclear complexes (2 and 8), is described. The ability of the larger metallacrown ethers (5−7, 11 and 12) to act as hosts to either dibenzyl- or di-n-butylammonium ions is investigated in solution (NMR and ESI-MS). Finally, several of these metallacrown ethers were found to possess in vitro antitumor activity on three tumor cell lines (liposarcoma, A549 and 518A2). The activity of these complexes, all of which were found to induce apoptotic cell death, is discussed relative to their structure and the findings of platinum uptake studies.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1706
TI  - Platinum(IV) complexes with α,ω-bis(pyrazol-1-yl) alkanediyl and diethyl ether/thioether ligands. Crystal structures of dibromodimethyl[1,2-bis(pyrazol-1-yl)ethane]platinum(IV) and trimethyl-bis[2-(pyrazol-1-yl)ethyl]etherplatinum(IV) tetrafluoroborate
JO  - Polyhedron
PY  - 2008
SP  - 3091-3096
AU  - Kelly, M. E.
AU  - Gómez-Ruiz, S.
AU  - Schmidt, J.
AU  - Wagner, C.
AU  - Schmidt, H.
AU  - 
VL  - 27
UR  - 
DO  - 10.1016/j.poly.2008.07.003
AB  - Reactions of the flexible α,ω-bis(pyrazol-1-yl) compounds 1,2-bis(pyrazol-1-yl)ethane (L1), 1,8-bis(pyrazol-1-yl)-n-octane (L2), bis[2-(pyrazol-1-yl)ethyl]ether (L3) and bis[2-(pyrazol-1-yl)ethyl]thioether (L4) with precursor organometallic platinum complexes ([(PtBr2Me2)n], [(PtIMe3)4] and [(PtMe2(cod)]/I2) are described herein. The spectroscopic characterization of the platinum(IV) products of these reactions [PtBr2Me2{pz(CH2)mpz}], m = 2 (1) or 8 (2), [PtI2Me2{pz(CH2)2pz}] (3), [PtMe3(pzCH2CH2OCH2CH2pz)][BF4] (4) and [PtMe3(pzCH2CH2SCH2CH2pz)][CF3SO3] (5), where ‘pz’ is pyrazol-1-yl, is discussed. Furthermore, solid state structures of 1, a complex with a seven-membered chelate ring, and 4, a complex bearing the neutral κ2N,N′,κO ligand bis[2-(pyrazol-1-yl)ethyl]ether (L3) are reported.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1705
TI  - Pyrone polyketides synthesized by a type III polyketide synthase from Drosophyllum lusitanicum
JO  - Phytochemistry
PY  - 2008
SP  - 3043-3053
AU  - Jindaprasert, A.
AU  - Springob, K.
AU  - Schmidt, J.
AU  - De-Eknamkul, W.
AU  - Kutchan, T. M.
AU  - 
VL  - 69
UR  - 
DO  - 10.1016/j.phytochem.2008.03.013
AB  - To isolate cDNAs involved in the biosynthesis of acetate-derived naphthoquinones in Drosophyllum lusitanicum, an expressed sequence tag analysis was performed. RNA from callus cultures was used to create a cDNA library from which 2004 expressed sequence tags were generated. One cDNA with similarity to known type III polyketide synthases was isolated as full-length sequence and termed DluHKS. The translated polypeptide sequence of DluHKS showed 51–67% identity with other plant type III PKSs. Recombinant DluHKS expressed in Escherichia coli accepted acetyl-coenzyme A (CoA) as starter and carried out sequential decarboxylative condensations with malonyl-CoA yielding α-pyrones from three to six acetate units. However, naphthalenes, the expected products, were not isolated. Since the main compound produced by DluHKS is a hexaketide α-pyrone, and the naphthoquinones in D. lusitanicum are composed of six acetate units, we propose that the enzyme provides the backbone of these secondary metabolites. An involvement of accessory proteins in this biosynthetic pathway is discussed.
A2  - 
C1  - Bioorganic Chemistry; Molecular Signal Processing
ER  - 


TY  - JOUR
ID  - 1701
TI  - Comparing Natural Product (NP) and non-NP datasets at an atomic scale
JO  - Chem. Cent. J.
PY  - 2008
SP  - P25
AU  - Heintz, T.
AU  - Brandt, W.
AU  - Weber, L.
AU  - Wessjohann, L. A.
AU  - 
VL  - 2
UR  - 
DO  - 10.1186/1752-153X-2-S1-P25
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1700
TI  - Quinolone alkaloids from Waltheria douradinha
JO  - Phytochemistry
PY  - 2008
SP  - 994-999
AU  - Gressler, V.
AU  - Stüker, C. Z.
AU  - Dias, G. d. O.
AU  - Dalcol, I. I.
AU  - Burrow, R. A.
AU  - Schmidt, J.
AU  - Wessjohann, L.
AU  - Morel, A. F.
AU  - 
VL  - 69
UR  - 
DO  - 10.1016/j.phytochem.2007.10.018
AB  - A phytochemical investigation of the stems of Waltheria douradinha resulted in isolation of two 4-quinolone alkaloids, waltherione B and vanessine, along with three known alkaloids, waltherione A, antidesmone and O-methyltembamide. Their structures were elucidated on the basis of their 2D NMR spectroscopic analyses, and from X-ray crystallographic analysis of waltherione A and the O-methyl derivative of waltherione B. Additionally, waltherione B and vanessine, and the O- and N-methyl derivatives of waltherione A and waltherione B, were evaluated for their antimicrobial activities; only vanessine displayed any (weak) antimicrobial activity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1698
TI  - Protein structure modeling indicates hexahistidine-tag interference with enzyme activity
JO  - Proteins
PY  - 2008
SP  - 173-183
AU  - Freydank, A.-C.
AU  - Brandt, W.
AU  - Dräger, B.
AU  - 
VL  - 72
UR  - 
DO  - 10.1002/prot.21905
AB  - Unusual kinetic characteristics of tropinone reductase, an enzyme in the family of short chain dehydrogenases, prompted to investigate a possible impact of the hexahistidine affinity tag on catalytic properties. Comparison of enzymes from Solanum dulcamara , Solanaceae, tagged at the N‐terminus or at the C‐terminus revealed that the C‐terminally tagged form was functionally impaired. Protein modeling indicated that the hexahistidine tag attached at the C‐terminus but not at the N‐terminus of the polypeptide can interfere with the active site by steric or electrostatic interactions. In consequence, protein modeling is suggested before enzyme expression with affinity tags to estimate possible interactions of affinity tags with the active center.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1697
TI  - RNA Interference-Mediated Repression of MtCCD1 in Mycorrhizal Roots of Medicago truncatula Causes Accumulation of C27 Apocarotenoids, Shedding Light on the Functional Role of CCD1
JO  - Plant Physiol.
PY  - 2008
SP  - 1267-1282
AU  - Floss, D. S.
AU  - Schliemann, W.
AU  - Schmidt, J.
AU  - Strack, D.
AU  - Walter, M. H.
AU  - 
VL  - 148
UR  - 
DO  - 10.1104/pp.108.125062
AB  - Tailoring carotenoids by plant carotenoid cleavage dioxygenases (CCDs) generates various bioactive apocarotenoids. Recombinant CCD1 has been shown to catalyze symmetrical cleavage of C40 carotenoid substrates at 9,10 and 9′,10′ positions. The actual substrate(s) of the enzyme in planta, however, is still unknown. In this study, we have carried out RNA interference (RNAi)-mediated repression of a Medicago truncatula CCD1 gene in hairy roots colonized by the arbuscular mycorrhizal (AM) fungus Glomus intraradices. As a consequence, the normal AM-mediated accumulation of apocarotenoids (C13 cyclohexenone and C14 mycorradicin derivatives) was differentially modified. Mycorradicin derivatives were strongly reduced to 3% to 6% of the controls, while the cyclohexenone derivatives were only reduced to 30% to 47%. Concomitantly, a yellow-orange color appeared in RNAi roots. Based on ultraviolet light spectra and mass spectrometry analyses, the new compounds are C27 apocarotenoic acid derivatives. These metabolic alterations did not lead to major changes in molecular markers of the AM symbiosis, although a moderate shift to more degenerating arbuscules was observed in RNAi roots. The unexpected outcome of the RNAi approach suggests C27 apocarotenoids as the major substrates of CCD1 in mycorrhizal root cells. Moreover, literature data implicate C27 apocarotenoid cleavage as the general functional role of CCD1 in planta. A revised scheme of plant carotenoid cleavage in two consecutive steps is proposed, in which CCD1 catalyzes only the second step in the cytosol (C27 → C14 + C13), while the first step (C40 → C27 + C13) may be catalyzed by CCD7 and/or CCD4 inside plastids.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1695
TI  - Tapetum-specific location of a cation-dependent O-methyltransferase in Arabidopsis thaliana
JO  - Plant J.
PY  - 2008
SP  - 132-145
AU  - Fellenberg, C.
AU  - Milkowski, C.
AU  - Hause, B.
AU  - Lange, P.-R.
AU  - Böttcher, C.
AU  - Schmidt, J.
AU  - Vogt, T.
AU  - 
VL  - 56
UR  - 
DO  - 10.1111/j.1365-313X.2008.03576.x
AB  - Cation‐ and S ‐adenosyl‐l ‐methionine (AdoMet)‐dependent plant natural product methyltransferases are referred to as CCoAOMTs because of their preferred substrate, caffeoyl coenzyme A (CCoA). The enzymes are encoded by a small family of genes, some of which with a proven role in lignin monomer biosynthesis. In Arabidopsis thaliana  individual members of this gene family are temporally and spatially regulated. The gene At1g67990  is specifically expressed in flower buds, and is not detected in any other organ, such as roots, leaves or stems. Several lines of evidence indicate that the At1g67990  transcript is located in the flower buds, whereas the corresponding CCoAOMT‐like protein, termed AtTSM1, is located exclusively in the tapetum of developing stamen. Flowers of At1g67990  RNAi‐suppressed plants are characterized by a distinct flower chemotype with severely reduced levels of the N  ′,N  ′′‐ bis‐(5‐hydroxyferuloyl)‐N  ′′′‐sinapoylspermidine compensated for by N1 ,N5 ,N10 ‐tris‐(5‐hydroxyferuloyl)spermidine derivative, which is characterized by the lack of a single methyl group in the sinapoyl moiety. This severe change is consistent with the observed product profile of AtTSM1 for aromatic phenylpropanoids. Heterologous expression of the recombinant protein shows the highest activity towards a series of caffeic acid esters, but 5‐hydroxyferuloyl spermidine conjugates are also accepted substrates. The in vitro  substrate specificity and the in vivo  RNAi‐mediated suppression data of the corresponding gene suggest a role of this cation‐dependent CCoAOMT‐like protein in the stamen/pollen development of A. thaliana .
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology; Molecular Signal Processing
ER  - 


TY  - JOUR
ID  - 1692
TI  - Non-volatile floral oils of Diascia spp. (Scrophulariaceae)
JO  - Phytochemistry
PY  - 2008
SP  - 1372-1383
AU  - Dumri, K.
AU  - Seipold, L.
AU  - Schmidt, J.
AU  - Gerlach, G.
AU  - Dötterl, S.
AU  - Ellis, A. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 69
UR  - 
DO  - 10.1016/j.phytochem.2007.12.012
AB  - The floral oils of Diascia purpurea, Diascia vigilis, Diascia cordata, Diascia megathura, Diascia integerrima and Diascia barberae (Scrophulariaceae) were selectively collected from trichome elaiophores. The derivatized floral oils were analyzed by gas chromatography–mass spectrometry (GC–MS), whilst the underivatized samples were analysed by electrospray ionization mass spectrometry (ESI-MS) and Fourier-transform ion cyclotron resonance mass spectrometry (FTICR-MS). The most common constituents of the floral oils investigated are partially acetylated acylglycerols of (3R)-acetoxy fatty acids (C14, C16, and C18), as was proven with non-racemic synthetic reference samples. The importance of these oils for Rediviva bees is discussed in a co-evolutionary context.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1690
TI  - 1-O-Substituted derivatives of murrayafoline A and their antifungal properties
JO  - Nat. Prod. Res.
PY  - 2008
SP  - 950-954
AU  - Cuong, N. M.
AU  - Wilhelm, H.
AU  - Porzel, A.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 22
UR  - 
DO  - 10.1080/14786410701650212
AB  - The synthesis of some 1-oxygenated derivatives of murrayafoline A (1) and their antifungal properties is reported. Three derivatives, 1-hydroxy-3-methyl-9H-carbazole (2), 1-(3-methylbut-2-enyloxy)-3-methyl-9H-carbazole (3) and 1-(2,3,4,6,-tetra-O-acetyl-α-D-O-glucopyranosyl)-3-methyl-9H-carbazole (4), of murrayafoline A were synthesized. Compounds 1 and 2 exhibit strong fungicidal activity against Cladosporium cucumerinum at the dose of 12.5 µg.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1687
TI  - Implication of HMGR in homeostasis of sequestered and de novo produced precursors of the iridoid biosynthesis in leaf beetle larvae
JO  - Insect Biochem. Mol. Biol.
PY  - 2008
SP  - 76-88
AU  - Burse, A.
AU  - Frick, S.
AU  - Schmidt, A.
AU  - Buechler, R.
AU  - Kunert, M.
AU  - Gershenzon, J.
AU  - Brandt, W.
AU  - Boland, W.
AU  - 
VL  - 38
UR  - 
DO  - 10.1016/j.ibmb.2007.09.006
AB  - Insects employ iridoids to deter predatory attacks. Larvae of some Chrysomelina species are capable to produce those cyclopentanoid monoterpenes de novo. The iridoid biosynthesis proceeds via the mevalonate pathway to geranyl diphospate (GDP) subsequently converted into 8-hydroxygeraniol-8-O-β-d-glucoside followed by the transformation into the defensive compounds. We tested whether the glucoside, its aglycon or geraniol has an impact on the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the key regulatory enzyme of the mevalonate pathway and also the iridoid biosynthesis. To address the inhibition site of the enzyme, initially a complete cDNA encoding full length HMGR was cloned from Phaedon cochleariae. Its catalytic portion was then heterologously expressed in Escherichia coli. Purification and characterization of the recombinant protein revealed attenuated activity in enzyme assays by 8-hydroxygeraniol whereas no effect has been observed by addition of the glucoside or geraniol. Thus, the catalytic domain is the target for the inhibitor. Homology modeling of the catalytic domain and docking experiments demonstrated binding of 8-hydroxygeraniol to the active site and indicated a competitive inhibition mechanism. Iridoid producing larvae are potentially able to sequester glucosidically bound 8-hydroxygeraniol whose cleavage of the sugar moiety results in 8-hydroxygeraniol. Therefore, HMGR may represent a regulator in maintenance of homeostasis between de novo produced and sequestered intermediates of iridoid metabolism. Furthermore, we demonstrated that HMGR activity is not only diminished in iridoid producers but most likely prevalent within the Chrysomelina subtribe and also within the insecta.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1685
TI  - The functional divergence of short-chain dehydrogenases involved in tropinone reduction
JO  - Plant J.
PY  - 2008
SP  - 388-401
AU  - Brock, A.
AU  - Brandt, W.
AU  - Dräger, B.
AU  - 
VL  - 54
UR  - 
DO  - 10.1111/j.1365-313X.2008.03422.x
AB  - Tropane alkaloids typically occur in the Solanaceae and are also found in Cochlearia officinalis , a member of the Brassicaceae. Tropinone reductases are key enzymes of tropane alkaloid metabolism. Two different tropinone reductases form one stereoisomeric product each, either tropine for esterified alkaloids or pseudotropine that is converted to calystegines. A cDNA sequence with similarity to known tropinone reductases (TR) was cloned from C. officinalis . The protein was expressed in Escherichia coli , and found to catalyze the reduction of tropinone. The enzyme is a member of the short‐chain dehydrogenase enzyme family and shows broad substrate specificity. Several synthetic ketones were accepted as substrates, with higher affinity and faster enzymatic turnover than observed for tropinone. C. officinalis  TR produced both the isomeric alcohols tropine and pseudotropine from tropinone using NADPH + H+ as co‐substrate. Tropinone reductases of the Solanaceae, in contrast, are strictly stereospecific and form one tropane alcohol only. The Arabidopsis thaliana  homologue of C. officinalis  TR showed high sequence similarity, but did not reduce tropinone. A tyrosine residue was identified in the active site of C. officinalis  TR that appeared responsible for binding and orientation of tropinone. Mutagenesis of the tyrosine residue yielded an active reductase, but with complete loss of TR activity. Thus C. officinalis  TR presents an example of an enzyme with relaxed substrate specificity, like short‐chain dehydrogenases, that provides favorable preconditions for the evolution of novel functions in biosynthetic sequences.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1684
TI  - A Structural Model of the Membrane-Bound Aromatic Prenyltransferase UbiA from E. coli
JO  - ChemBioChem
PY  - 2008
SP  - 982-992
AU  - Bräuer, L.
AU  - Brandt, W.
AU  - Schulze, D.
AU  - Zakharova, S.
AU  - Wessjohann, L.
AU  - 
VL  - 9
UR  - 
DO  - 10.1002/cbic.200700575
AB  - We report the first reasonable model for the active site of the membrane‐bound aromatic prenyltransferase UbiA, derived from structural—not sequence—similarity to a terpene synthase, with the aid of threading, site‐directed mutagenesis, and substrate selectivities. The high similarity of the active fold of UbiA‐transferase to that of 5‐epi‐aristolochene synthase (Nictotiana tabacum ), despite a low homology, allows a hypothesis on a convergent evolution of these enzymes to be formed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1683
TI  - Acceleration of Arylzinc Formation and Its Enantioselective Addition to Aldehydes by Microwave Irradiation and Aziridine-2-methanol Catalysts
JO  - J. Org. Chem.
PY  - 2008
SP  - 2879-2882
AU  - Braga, A. L.
AU  - Paixão, M. W.
AU  - Westermann, B.
AU  - Schneider, P. H.
AU  - Wessjohann, L. A.
AU  - 
VL  - 73
UR  - 
DO  - 10.1021/jo702413n
AB  - The formation and 2-amino alcohol catalyzed addition of arylzinc reagents from and with boronic acids, respectively, is drastically accelerated to a few minutes under microwave irradiation without loss of enantioselectivity (up to 98% ee). Of the amino acid derived catalysts tested, the conformationally restricted bulky substituted aziridine-2-methanols derived from serine show the best overall performance in the formation of diarylmethanols.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1681
TI  - Metabolome Analysis of Biosynthetic Mutants Reveals a Diversity of Metabolic Changes and Allows Identification of a Large Number of New Compounds in Arabidopsis
JO  - Plant Physiol.
PY  - 2008
SP  - 2107-2120
AU  - Böttcher, C.
AU  - von Roepenack-Lahaye, E.
AU  - Schmidt, J.
AU  - Schmotz, C.
AU  - Neumann, S.
AU  - Scheel, D.
AU  - Clemens, S.
AU  - 
VL  - 147
UR  - 
DO  - 10.1104/pp.108.117754
AB  - Metabolomics is facing a major challenge: the lack of knowledge about metabolites present in a given biological system. Thus, large-scale discovery of metabolites is considered an essential step toward a better understanding of plant metabolism. We show here that the application of a metabolomics approach generating structural information for the analysis of Arabidopsis (Arabidopsis thaliana) mutants allows the efficient cataloging of metabolites. Fifty-six percent of the features that showed significant differences in abundance between seeds of wild-type, transparent testa4, and transparent testa5 plants could be annotated. Seventy-five compounds were structurally characterized, 21 of which could be identified. About 40 compounds had not been known from Arabidopsis before. Also, the high-resolution analysis revealed an unanticipated expansion of metabolic conversions upstream of biosynthetic blocks. Deficiency in chalcone synthase results in the increased seed-specific biosynthesis of a range of phenolic choline esters. Similarly, a lack of chalcone isomerase activity leads to the accumulation of various naringenin chalcone derivatives. Furthermore, our data provide insight into the connection between p-coumaroyl-coenzyme A-dependent pathways. Lack of flavonoid biosynthesis results in elevated synthesis not only of p-coumarate-derived choline esters but also of sinapate-derived metabolites. However, sinapoylcholine is not the only accumulating end product. Instead, we observed specific and sophisticated changes in the complex pattern of sinapate derivatives.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1680
TI  - One-Pot Multicomponent Synthesis of N-Substituted Tryptophan-Derived Diketopiperazines
JO  - Synthesis
PY  - 2008
SP  - 2077-2082
AU  - Bohn Rhoden, C. R.
AU  - Westermann, B.
AU  - Wessjohann, L.
AU  - 
VL  - 2008
UR  - 
DO  - 10.1055/s-2008-1067112
AB  - A simple, rapid, one-pot multicomponent synthesis of tryptophan-derived diketopiperazines with variable side chains is presented. Microwave radiation gives comparable yields, but allows a significant decrease in reaction times.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1678
TI  - Antifungal rosane diterpenes and other constituents of Hugonia castaneifolia
JO  - Phytochemistry
PY  - 2008
SP  - 200-205
AU  - Baraza, L. D.
AU  - Joseph, C. C.
AU  - Munissi, J. J.
AU  - Nkunya, M. H.
AU  - Arnold, N.
AU  - Porzel, A.
AU  - Wessjohann, L.
AU  - 
VL  - 69
UR  - 
DO  - 10.1016/j.phytochem.2007.06.021
AB  - The rosane diterpenoids hugorosenone [3β-hydroxyrosa-1(10),15-dien-2-one], 18-hydroxyhugorosenone and 18-hydroxy-3-deoxyhugorosenone, and 12-hydroxy-13-methylpodocarpa-8,11,13-trien-3-one were isolated as antifungal constituents of H. castaneifolia Engl. root bark, together with the previously reported di-podocarpanoids hugonone A and hugonone B that were weakly active, and 1(10),15-rosadiene-2β,3β-diol (hugorosenol), 4α-methoxyhimachal-10-en-5β-ol (hugonianene B) and 2-hydroxyhenpentacont-2-enal, and the known compounds tetracosyl-(E)-ferrulate and caryophyllene oxide, all of which were inactive. Hugorosenone also exhibited activity against Anopheles gambiae mosquito larvae. Structural determination was achieved based on spectroscopic data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1676
TI  - Essential Oil Composition from Oleogum Resin of Soqotraen Commiphora kua
JO  - Rec. Nat. Prod.
PY  - 2008
SP  - 70-75
AU  - Ali, N. A. A.
AU  - Wurster, M.
AU  - Arnold, N.
AU  - Lindequist, U.
AU  - Wessjohann, L.
AU  - 
VL  - 2
UR  - http://www.acgpubs.org/article/records-of-natural-products/2008/3-july-september/essential-oil-composition-from-oleogum-resin-of-soqotraen-commiphorakua
AB  - The major constituents of the essential oil obtained by hydrodistillation from the oleogum resin of Commiphora kua Vollesen were identified by GC-MS. Sixteen constituents were detected from the essential oil, which constituted about (90.5%) of the total amount. Major constituents of the oil were α- cadinol (33.0%), g -cadinene (22.5%), d -cadinene (17.0%), isocaryophyllene (3.7%), allo-aromadendrene (2.8%), α-muurolene (2.7%), and α-humulene (2.4%). The Oil of Commiphora kua showed moderate antifungal activity against Cladosporium cucumerinum.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1675
TI  - Chemical Composition of the Essential Oil of Teucrium yemense Deflers
JO  - Rec. Nat. Prod.
PY  - 2008
SP  - 25-32
AU  - Ali, N. A. A.
AU  - Wurster, M.
AU  - Arnold, N.
AU  - Lindequist, U.
AU  - Wessjohann, L.
AU  - 
VL  - 2
UR  - http://www.acgpubs.org/article/records-of-natural-products/2008/2-april-june/chemical-composition-of-the-essential-oil-of-teucrium-yemense-deflers
AB  - The chemical composition of the essential oil (EO) obtained by hydrodistillation from the leaves of Teucrium yemense Deflers was determined by GC-MS. Twelve compounds accounting to 77.7% of the total oil were identified. Sesquiterpene hydrocarbons (73.9%) were the predominant portion of the oil with δ-cadinene (34.9%), β-caryophyllene (22.7%), a -humulene (6.1%), and a -selinene (5.4%) as the main constituents.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1674
TI  - Chemical Composition and Biological Activities of Essential Oils from the Oleogum Resins of Three Endemic Soqotraen Boswellia Species
JO  - Rec. Nat. Prod.
PY  - 2008
SP  - 6-12
AU  - Ali, N. A. A.
AU  - Wurster, M.
AU  - Arnold, N.
AU  - Teichert, A.
AU  - Schmidt, J.
AU  - Lindequist, U.
AU  - Wessjohann, L.
AU  - 
VL  - 2
UR  - http://www.acgpubs.org/article/records-of-natural-products/2008/1-january-march/chemical-composition-and-biological-activities-of-essential-oils-from-the-oleogum-resins-of-three-endemic-soqotraen-boswellia-species
AB  - The chemical composition, antioxidant and anticholinesterase activity of three essential oils (EOs) obtained from the oleogum resin of three endemic Sqotraen Boswellia species, Boswellia socotrana Balf. f, Boswellia ameero Balf. f, andBoswellia elongata Balf. f were determined. GC-MS technique was used for the analysis of the oils. Oils of B. socotrana and B. ameero were characterized by a high content of monoterpenes. The main constituens of B. socotrana and B. ameero were (E)-2,3-epoxycarene (51.8%), 1,5-isopropyl-2-methylbicyclo[3.1.0]hex-3-en-2-ol (31.3%), and a -cymene (7.1%); (3E,5E)-2,6-dimethyl-1,3,5,7-octatetraene (34.9%), 1-(2,4-Dimethylphenyl)ethanol (20.3%), 3,4-dimethylstyrene (17.3%), a -campholenal (13.4%) and a -terpineol (12.4%) respectively. The composition of B. elongata oil was dominated by the diterpene verticiol (52.4%), the sesquiterpene caryophellene (39.1%) and methylcycloundecanecarboxylate (7.8%). The oils were screened for their antioxidant activity by using the DPPH free radical scavenger assay and their anticholinesterase activity on acetylcholinesterase enzyme by using in vitro Ellman method. The antioxidant activity of EOs from B. socotrana (IC 50 =121.4 µg/mL) appeared to be more potent than that of B. elongata (IC 50 =211.2 µg/mL) and B. ameero (IC 50 =175.2 µg/mL). EO of B. socotrana showed the higher AChE inhibitory activity with 59.3% at concentration of 200 μ g/mL in comparison to EOs of B. elongata and B. ameero (29.6, 41.6 enzyme inhibition) respectively.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1778
TI  - Corrigendum: Total Synthesis of Tubulysin U and V
JO  - Angew. Chem. Int. Ed.
PY  - 2007
SP  - 2347-2348
AU  - Dömling, A.
AU  - Beck, B.
AU  - Eichelberger, U.
AU  - Sakamuri, S.
AU  - Menon, S.
AU  - Chen, Q.-Z.
AU  - Lu, Y.
AU  - Wessjohann, L.
AU  - 
VL  - 46
UR  - 
DO  - 10.1002/anie.200790053
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1777
TI  - Berichtigung: Total Synthesis of Tubulysin U and V
JO  - Angew. Chem.
PY  - 2007
SP  - 2399-2400
AU  - Dömling, A.
AU  - Beck, B.
AU  - Eichelberger, U.
AU  - Sakamuri, S.
AU  - Menon, S.
AU  - Chen, Q.-Z.
AU  - Lu, Y.
AU  - Wessjohann, L.
AU  - 
VL  - 119
UR  - 
DO  - 10.1002/ange.200790053
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1769
TI  - Aziridine-Modified Amino Alcohols as Efficient Modular Catalysts for Highly Enantioselective Alkenylzinc Additions to Aldehydes
JO  - Synlett
PY  - 2007
SP  - 0917-0920
AU  - Braga, A.
AU  - Paixao, M.
AU  - Westermann, B.
AU  - Schneider, P.
AU  - Wessjohann, L.
AU  - 
VL  - 2007
UR  - 
DO  - 10.1055/s-2007-973879
AB  - N-Tritylaziridino alcohols have been easily synthesized in a straightforward synthetic route from an inexpensive and easily available chiral pool. They were used in the enantioselective alkenylzinc additions to aldehydes furnishing the products in excellent yields and stereoselectivities up to 97%.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1765
TI  - Lukten hos naftalinskinnet, Scytinostroma portentosum
JO  - Svensk Mykologisk Tidskrift
PY  - 2007
SP  - 49-53
AU  - Arnold, N.
AU  - Schmidt, J.
AU  - Kuhnt, C.
AU  - Wessjohann, L.
AU  - 
VL  - 28
UR  - https://www.svampar.se/smf/smt/SMT_2007_2.pdf
AB  - The naphthalene-like smell of Scytinostroma portentosum (Berk. &amp; Curt.) Donk originates predominantly from indole (1) together with 3-chloroindole (3) and to a lesser extent of 1-octen-3-ol (9). Naphthalene (8) itself could not be detected.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1764
TI  - Chemical constituents of Zizyphus sativa Gaertn fruits. Part III - Alkaloids
JO  - Vietnam J. Chem.
PY  - 2007
SP  - 237-240
AU  - Anh, N. T. H.
AU  - Sung, T. V.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 45
UR  - http://vjs.ac.vn/index.php/vjchem/article/view/4744
AB  - Two alkaloids have been isolated from Z. sativa fruits besides butane-2,3-diol and glycerol. The structures of alkaloids were established as stepharine and 1,2-dimethoxy,5,6,6a,7-tetrahydro-4H-dibenzo-quinoline by using MS, NMR spectroscopic data and by comparison with reported data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1763
TI  - Chemical constituents of Zizyphus sativa Gaertn fruits. Part II - Triterpenoid acid
JO  - Vietnam J. Chem.
PY  - 2007
SP  - 110-113
AU  - Anh, N. T. H.
AU  - Sung, T. V.
AU  - Wessjohann, L.
AU  - 
VL  - 45
UR  - http://vjs.ac.vn/index.php/vjchem/article/view/4720
AB  - Three terpenoid acids have been isolated from an ethyl acetate extract of Z. sativa fruits. Their structures were established as betulinic, oleanolic and maslinic acids by means of MS, NMR spectroscopic data and by comparison with reported data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1762
TI  - Improved Mutasynthetic Approaches for the Production of Modified Aminocoumarin Antibiotics
JO  - Chem. Biol.
PY  - 2007
SP  - 955-967
AU  - Anderle, C.
AU  - Hennig, S.
AU  - Kammerer, B.
AU  - Li, S.-M.
AU  - Wessjohann, L.
AU  - Gust, B.
AU  - Heide, L.
AU  - 
VL  - 14
UR  - 
DO  - 10.1016/j.chembiol.2007.07.014
AB  - This study reports improved mutasynthetic approaches for the production of aminocoumarin antibiotics. Previously, the mutasynthetic production of aminocoumarins with differently substituted benzoyl moieties was limited by the substrate specificity of the amide synthetase CloL. We expressed two amide synthetases with different substrate specificity, CouL and SimL, in appropriately engineered producer strains. After feeding of precursor analogs that were not accepted by CloL, but by SimL or CouL, a range of aminocoumarins, unattainable in our previous experiments, was produced and isolated in preparative amounts. Further, we developed a two-stage mutasynthesis procedure for the production of hybrid antibiotics that showed the substitution pattern of novobiocin in the aminocoumarin moiety and that of clorobiocin in the deoxysugar moiety. The substitution pattern of the benzoyl moiety was determined by external addition of an appropriate precursor. Twenty-five aminocoumarin compounds were prepared by these methods, and their structures were elucidated with mass and 1H-NMR spectroscopy.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1760
TI  - Synthesis of 3,4-disaccharides from pyranosides and furanosides monomers, a novel class of potential bioactive disaccharides
JO  - ARKIVOC
PY  - 2007
SP  - 329
AU  - Abbas, M.
AU  - Westermann, B.
AU  - Voelter, W.
AU  - 
VL  - 2007
UR  - 
DO  - 10.3998/ark.5550190.0008.729
AB  - A new class of synthetically and pharmacologically important disaccharides containing epoxide moieties were synthesized from pyranoside and furanoside monomers in good to excellent yields. The scope and limitations for the formation of the linkage were evaluated.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1811
TI  - The application of chiral, non-racemic N-alkylephedrine and N,N-dialkylnorephedrine as ligands for the enantioselective aryl transfer reaction to aldehydes
JO  - J. Mol. Catal. A
PY  - 2007
SP  - 120-124
AU  - Paixão, M. W.
AU  - de Godoi, M.
AU  - Rhoden, C. R.
AU  - Westermann, B.
AU  - Wessjohann, L. A.
AU  - Lüdtke, D. S.
AU  - Braga, A. L.
AU  - 
VL  - 261
UR  - 
DO  - 10.1016/j.molcata.2006.07.076
AB  - The catalytic enantioselective arylation of several aldehydes using arylboronic acids as the source of transferable aryl groups is described; the reaction is found to proceed in excellent yields and high enantioselectivities (up to 96% ee) in the presence of a chiral amino alcohol derived from ephedrines and congeners.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1806
TI  - Studies on chemical constituents of the roots of Polygala sp.: II - Further phenylpropanoide sucrose esters
JO  - Vietnam J. Chem.
PY  - 2007
SP  - 518-522
AU  - Ninh, P. T.
AU  - Anh, N. T. H.
AU  - Sung, T. V.
AU  - Wessjohann, L.
AU  - 
VL  - 45
UR  - http://vjs.ac.vn/index.php/vjchem/issue/view/384
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1805
TI  - The chemical constitutents of Vietnamese medicinal plant Ophiopogon Japonicus
JO  - Tap chi Phan tich Hoa
PY  - 2007
SP  - 59-64
AU  - Nguyen, T. H. A.
AU  - 
VL  - 9
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1804
TI  - Screening of some Solanaceae plants for cytotoxic activity, and isolation and structure elucidation of a new steroid from the active fraction of Physalis divarivata D. Don
JO  - Planta Med.
PY  - 2007
SP  - P_422
AU  - Namjooyan, F.
AU  - Azemi, M.
AU  - Mosaddegh, M.
AU  - Cheraghali, A.
AU  - Kobarfard, F.
AU  - Porzel, A.
AU  - 
VL  - 73
UR  - 
DO  - 10.1055/s-2007-987202
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1802
TI  - One-Step Synthesis of Natural Product-Inspired Biaryl Ether-Cyclopeptoid Macrocycles by Double Ugi Multiple-Component Reactions of Bifunctional Building Blocks
JO  - Eur. J. Org. Chem.
PY  - 2007
SP  - 149-157
AU  - Michalik, D.
AU  - Schaks, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 2007
UR  - 
DO  - 10.1002/ejoc.200600354
AB  - Isonitrile‐functionalized biaryl ethers can serve as key building blocks for the highly efficient one‐step production of natural product inspired‐macrocycles, with six or even twelve new bonds and rings with up to 50 members being formed in total yields of up to 51 %. Aliphatic diamine and diacid tethers give access to two different classes of N ‐substituted biaryl ether cyclopeptides, suitable for library construction. As part of a conceptual work on MiBs (m ultiple m ulticomponent m acrocyclizations/m acrocycles i ncluding b ifunctional b uilding b locks), the influence of length and type of flexible tethers on the propensity for cyclization is studied.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1799
TI  - A Stable, Convertible Isonitrile as a Formic Acid Carbanion [-COOH] Equivalent and Its Application in Multicomponent Reactions
JO  - Synlett
PY  - 2007
SP  - 3188-3192
AU  - Kreye, O.
AU  - Westermann, B.
AU  - Wessjohann, L.
AU  - 
VL  - 2007
UR  - 
DO  - 10.1055/s-2007-990912
AB  - The application of 2-(2,2-dimethoxyethyl) phenyl iso­nitrile in Ugi, Passerini, and Ugi-Smiles reactions is described. The simple transformation to highly activated indolyl amides allows functional-group conversion of the isonitrile moiety into a variety of carboxylic acid derivatives, overall acting as a neutral, nucleophilic COOH equivalent.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1798
TI  - Phytoconstituents from the root of Streptocaulon tomentosum and their chemotaxonomical relevance for separation from S. juventas
JO  - Biochem. Syst. Ecol.
PY  - 2007
SP  - 517-524
AU  - Khine, M. M.
AU  - Arnold, N.
AU  - Franke, K.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Wessjohann, L.
AU  - 
VL  - 35
UR  - 
DO  - 10.1016/j.bse.2007.01.006
AB  - A new cardenolide, 17β-H-periplogenin-3-O-β-d-digitoxoside (1), and a new pregnane glycoside, Δ5-pregnene-3β,16α-diol-d-O-[2,4-O-diacetyl-β-digitalopyranosyl-(1 → 4)-β-d-cymaropyranoside]-16-O-[β-d-glucopyranoside] (2) were isolated from the roots of Streptocaulon tomentosum (Asclepiadaceae) together with a series of known compounds. Their chemotaxonomic significance for the separation of S. tomentosum from Streptocaulon juventas is discussed, suggesting a rather clear distinction of these species.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1797
TI  - Homology Modeling of Human Fyn Kinase Structure: Discovery of Rosmarinic Acid as a New Fyn Kinase Inhibitor and in Silico Study of Its Possible Binding Modes
JO  - J. Med. Chem.
PY  - 2007
SP  - 1090-1100
AU  - Jelić, D.
AU  - Mildner, B.
AU  - Koštrun, S.
AU  - Nujić, K.
AU  - Verbanac, D.
AU  - Čulić, O.
AU  - Antolović, R.
AU  - Brandt, W.
AU  - 
VL  - 50
UR  - 
DO  - 10.1021/jm0607202
AB  - Tyrosine phosphorylation represents a unique signaling process that controls metabolic pathways, cell activation, growth and differentiation, membrane transport, apoptosis, neural, and other functions. We present here the three-dimensional structure of Fyn tyrosine kinase, a Src-family enzyme involved in T-cell receptor signal transduction. The structure of Fyn was modeled for homology using the Sybyl-Composer suite of programs for modeling. Procheck and Prosa II programs showed the high quality of the obtained three-dimensional model. Rosmarinic acid, a secondary metabolite of herbal plants, was discovered as a new Fyn kinase inhibitor using immunochemical and in silico methods. Two possible binding modes of rosmarinic acid were evaluated here, i.e., near to or in the ATP-binding site of kinase domain of Fyn. Enzyme kinetic experiments revealed that Fyn is inhibited by a linear-mixed noncompetitive mechanism of inhibition by rosmarinic acid. This indicates that rosmarinic acid binds to the second “non-ATP” binding site of the Fyn tyrosine kinase.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1796
TI  - Kopetdaghins A−E, Sesquiterpene Derivatives from the Aerial Parts and the Roots of Dorema kopetdaghense
JO  - J. Nat. Prod.
PY  - 2007
SP  - 1240-1243
AU  - Iranshahi, M.
AU  - Shaki, F.
AU  - Mashlab, A.
AU  - Porzel, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 70
UR  - 
DO  - 10.1021/np070043u
AB  - Three new sesquiterpene derivatives, kopetdaghins A−C (1−3), one known prenylated coumarin (7), and two known steroid glucosides, sitosterol 3-O-glucoside and stigmasterol 3-O-glucoside, were isolated from the aerial parts of Dorema kopetdaghense. In addition, two new sesquiterpene derivatives, kopetdaghin D (4) and kopetdaghin E (5), together with kopetdaghins A−C and one known sesquiterpene coumarin (6), were isolated from the roots of the plant. The structures of these compounds were elucidated by various 1D and 2D NMR techniques as well as high-resolution positive-ion ESIMS.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1795
TI  - Duplicate detection of 2D-NMR Spectra
JO  - J. Integr. Bioinformatics
PY  - 2007
SP  - 64-80
AU  - Hinneburg, A.
AU  - Egert, B.
AU  - Porzel, A.
AU  - 
VL  - 4
UR  - 
DO  - 10.1515/jib-2007-53
AB  - 2D-Nuclear magnetic resonance (NMR) spectra are used in the (structural) analysis of small molecules. In contrast to 1D-NMR spectra, 2D-NMR spectra correlate the chemical shifts of 1H and 13C at the same time. A spectrum consists of several peaks in a two--dimensional space. The most important information of a peak is the location of its center, which captures the bonding relationships of hydrogen and carbon atoms. A spectrum contains much information about the chemical structure of a product, but in most cases the structure cannot be read off in a simple and straightforward manner. Structure elucidation involves a considerable amount (manual) efforts.Using high-field NMR spectrometers, many 2D-NMR spectra can be recorded in short time. So the common situation is that a lab or company has a repository of 2D-NMR spectra, partially annotated with the structural information. For the remaining spectra the structure in unknown. In case two research labs are collaborating, the repositories will be merged and annotations shared.We reduce that problem to the task of finding duplicates in a given set of 2D-NMR spectra. Therefore, we propose a simple but robust definition of 2D-NMR duplicates, which allows for small measurement errors. We give a quadratic algorithm for the problem, which can be implemented in SQL. Further, we analyze a more abstract class of heuristics, which are based on selecting particular peaks. Such a heuristic works as a filter step on the pairs of possible duplicates and allows false positives. We compare all methods with respect to their run time. Finally we discuss the effectiveness of the duplicate definition on real data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1788
TI  - Triterpenoids from Gouania ulmifolia
JO  - Planta Med.
PY  - 2007
SP  - 499-501
AU  - Giacomelli, S.
AU  - Maldaner, G.
AU  - Stücker, C.
AU  - Marasciulo, C.
AU  - Schmidt, J.
AU  - Wessjohann, L.
AU  - Dalcol, I.
AU  - Morel, A.
AU  - 
VL  - 73
UR  - 
DO  - 10.1055/s-2007-967166
AB  - Two new triterpenoids, named gouanic acid A (1) and gouanic acid B (2), were isolated from the aerial parts of Gouania ulmifolia, along with six known compounds. The structures of the new compounds were determined by spectroscopic methods, mainly NMR (1D and 2D) and mass spectrometry. The new compounds did not show significant antimicrobial activities.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1787
TI  - Molecular Modeling and Site-Directed Mutagenesis Reveal the Benzylisoquinoline Binding Site of the Short-Chain Dehydrogenase/Reductase Salutaridine Reductase
JO  - Plant Physiol.
PY  - 2007
SP  - 1493-1503
AU  - Geissler, R.
AU  - Brandt, W.
AU  - Ziegler, J.
AU  - 
VL  - 143
UR  - 
DO  - 10.1104/pp.106.095166
AB  - Recently, the NADPH-dependent short-chain dehydrogenase/reductase (SDR) salutaridine reductase (E.C. 1.1.1.248) implicated in morphine biosynthesis was cloned from Papaver somniferum. In this report, a homology model of the Papaver bracteatum homolog was created based on the x-ray structure of human carbonyl reductase 1. The model shows the typical α/β-folding pattern of SDRs, including the four additional helices αF′-1 to αF′-4 assumed to prevent the dimerization of the monomeric short-chain dehyrogenases/reductases. Site-directed mutagenesis of asparagine-152, serine-180, tyrosine-236, and lysine-240 resulted in enzyme variants with strongly reduced performance or inactive enzymes, showing the involvement of these residues in the proton transfer system for the reduction of salutaridine. The strong preference for NADPH over NADH could be abolished by replacement of arginine residues 44 and 48 by glutamic acid, confirming the interaction between the arginines and the 2′-phosphate group. Docking of salutaridine into the active site revealed nine amino acids presumably responsible for the high substrate specificity of salutaridine reductase. Some of these residues are arranged in the right position by an additional αE′ helix, which is not present in SDRs analyzed so far. Enzyme kinetic data from mutagenic replacement emphasize the critical role of these residues in salutaridine binding and provide the first data on the molecular interaction of benzylisoquinoline alkaloids with enzymes.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1844
TI  - Natural Product Inspired meta/para’-Biaryl Ether Lactam Macrocycles by Double Ugi Multicomponent Reactions
JO  - Heterocycles
PY  - 2007
SP  - 863-872
AU  - Westermann, B.
AU  - Michalik, D.
AU  - Schaks, A.
AU  - Kreye, O.
AU  - Wagner, C.
AU  - Merzweiler, K.
AU  - Wessjohann, L. A.
AU  - 
VL  - 73
UR  - 
DO  - 10.3987/COM-07-S(U)21
AB  - Isonitrile meta/para’-functionalized biaryl ethers can serve as key building blocks for the highly efficient and diverse one step production of natural product inspired peptide/peptoid macrocycles, thereby forming up to 54-membered rings with eight or even sixteen new bonds. Aliphatic diamine and diacid tethers give access to two different classes of biaryl ether cyclopeptoids, either with exo/endo or exclusively endo dipeptidic moieties.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1843
TI  - The Chromium(II)-Mediated Coupling of Secondary Alkylhalides with Aromatic Aldehydes
JO  - Synlett
PY  - 2007
SP  - 2139-2141
AU  - Wessjohann, L.
AU  - Schmidt, G.
AU  - Schrekker, H.
AU  - 
VL  - 2007
UR  - 
DO  - 10.1055/s-2007-984887
AB  - The scope of chromium(II)-mediated Takai-Utimoto ­reactions was extended to previously unconvertable secondary alkylhalides. Optimization allowed yields of up to over 95%.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1842
TI  - Takai–Utimoto reactions of oxoalkylhalides catalytic in chromium and cobalt
JO  - Tetrahedron Lett.
PY  - 2007
SP  - 4323-4325
AU  - Wessjohann, L. A.
AU  - Schrekker, H. S.
AU  - 
VL  - 48
UR  - 
DO  - 10.1016/j.tetlet.2007.04.119
AB  - The scope of chromium(II)/cobalt(I)-catalyzed Takai–Utimoto reactions was extended to substrates with unprotected reactive functional groups. In the presence of a higher chlorosilane and manganese the first chromium(II)/cobalt(I)-catalyzed version for the coupling of oxoalkylhalides with aldehydes resulted.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1834
TI  - Isolation of fatty acids and aromatics from cell suspension cultures of Lavandula angustifolia
JO  - Nat. Prod. Res.
PY  - 2007
SP  - 100-105
AU  - Topçu, G.
AU  - Herrmann, G.
AU  - Kolak, U.
AU  - Gören, C.
AU  - Porzel, A.
AU  - Kutchan, T. M.
AU  - 
VL  - 21
UR  - 
DO  - 10.1080/14786410500462884
AB  - Cell suspension cultures of Lavandula angustifolia Mill. ssp. angustifolia (syn.: L. officinalis Chaix.) afforded a fatty acid composition, cis and trans p-coumaric acids (=p-hydroxy cinnamic acids), and β-sitosterol. The fatty acid composition was analyzed by GC-MS, and the structures of the isolated three compounds were determined by 1H- and 13C-NMR, and MS spectroscopic techniques.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1833
TI  - Study on chemical composition of the seeds of Zizyphus Jujuba Mill var. Spinosa Hu
JO  - Tap chi Duoc lieu
PY  - 2007
SP  - 11-13
AU  - Thuy, T. T.
AU  - Sung, T. V.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - 
VL  - 12
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1832
TI  - Flavonone-C-glycosides from the seeds of Zizyphus Jujuba Mill var. Spinosa Hu
JO  - Vietnam J. Chem.
PY  - 2007
SP  - 1-8
AU  - Thuy, T. T.
AU  - Sung, T. V.
AU  - Franke, K.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1830
TI  - Putrescine N-methyltransferases—a structure–function analysis
JO  - Plant Mol. Biol.
PY  - 2007
SP  - 787-801
AU  - Teuber, M.
AU  - Azemi, M. E.
AU  - Namjoyan, F.
AU  - Meier, A.-C.
AU  - Wodak, A.
AU  - Brandt, W.
AU  - Dräger, B.
AU  - 
VL  - 63
UR  - 
DO  - 10.1007/s11103-006-9126-7
AB  - Putrescine N-methyltransferase (PMT) is a key enzyme of plant secondary metabolism at the start of the specific biosynthesis of nicotine, of tropane alkaloids, and of calystegines that are glycosidase inhibitors with nortropane structure. PMT is assumed to have developed from spermidine synthases (SPDS) participating in ubiquitous polyamine metabolism. In this study decisive differences between both enzyme families are elucidated. PMT sequences were known from four Solanaceae genera only, therefore additional eight PMT cDNA sequences were cloned from five Solanaceae and a Convolvulaceae. The encoded polypeptides displayed between 76% and 97% identity and typical amino acids different from plant spermidine synthase protein sequences. Heterologous expression of all enzymes proved catalytic activity exclusively as PMT and K cat values between 0.16 s−1 and 0.39 s−1. The active site of PMT was initially inferred from a protein structure of spermidine synthase obtained by protein crystallisation. Those amino acids of the active site that were continuously different between PMTs and SPDS were mutated in one of the PMT sequences with the idea of changing PMT activity into spermidine synthase. Mutagenesis of active site residues unexpectedly resulted in a complete loss of catalytic activity. A protein model of PMT was based on the crystal structure of SPDS and suggests that overall protein folds are comparable. The respective cosubstrates S-adenosylmethionine and decarboxylated S-adenosylmethionine, however, appear to bind differentially to the active sites of both enzymes, and the substrate putrescine adopts a different position.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1828
TI  - Brunneins A–C, β-Carboline Alkaloids from Cortinarius brunneus
JO  - J. Nat. Prod.
PY  - 2007
SP  - 1529-1531
AU  - Teichert, A.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 70
UR  - 
DO  - 10.1021/np070259w
AB  - Four β-carboline alkaloids, brunneins A–C (1–3) and 3-(7-hydroxy-9H-β-carboline-1-yl)propanoic acid (4), were isolated from fruiting bodies of the agaricoid fungus Cortinarius brunneus. The structures of 1–3 were determined by analysis of NMR and MS data, and the structure of compound 4 was determined by comparison with published data. Brunnein A (1) exhibited very low cholinesterase inhibitory effects and no cytotoxicity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1825
TI  - Corrigendum to “Structure determinants and substrate recognition of serine carboxypeptidase-like acyltransferases from plant secondary metabolism” [FEBS Lett. 580 (2006) 6366-6374]
JO  - FEBS Lett.
PY  - 2007
SP  - 164-165
AU  - Stehle, F.
AU  - Brandt, W.
AU  - Milkowski, C.
AU  - Strack, D.
AU  - 
VL  - 581
UR  - 
DO  - 10.1016/j.febslet.2006.12.001
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1824
TI  - A polyketide synthase of Plumbago indica that catalyzes the formation of hexaketide pyrones
JO  - FEBS J.
PY  - 2007
SP  - 406-417
AU  - Springob, K.
AU  - Samappito, S.
AU  - Jindaprasert, A.
AU  - Schmidt, J.
AU  - Page, J. E.
AU  - De-Eknamkul, W.
AU  - Kutchan, T. M.
AU  - 
VL  - 274
UR  - 
DO  - 10.1111/j.1742-4658.2006.05588.x
AB  - Plumbago indica L. contains naphthoquinones that are derived from six acetate units. To characterize the enzyme catalyzing the first step in the biosynthesis of these metabolites, a cDNA encoding a type III polyketide synthase (PKS) was isolated from roots of P. indica. The translated polypeptide shared 47–60% identical residues with PKSs from other plant species. Recombinant P. indica PKS expressed in Escherichia coli  accepted acetyl‐CoA as starter and carried out five decarboxylative condensations with malonyl coenzyme A (‐CoA). The resulting hexaketide was not folded into a naphthalene derivative. Instead, an α‐pyrone, 6‐(2′,4′‐dihydroxy‐6′‐methylphenyl)‐4‐hydroxy‐2‐pyrone, was produced. In addition, formation of α‐pyrones with linear keto side chains derived from three to six acetate units was observed. As phenylpyrones could not be detected in P. indica roots, we propose that the novel PKS is involved in the biosynthesis of naphthoquinones, and additional cofactors are probably required for the biosynthesis of these secondary metabolites in vivo.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1822
TI  - Influence of pH and flanking serine on the redox potential of S-S and S-Se bridges of Cys-Cys and Cys-Sec peptides
JO  - Biol. Chem.
PY  - 2007
SP  - 1099-1101
AU  - Schneider, A.
AU  - Brandt, W.
AU  - Wessjohann, L. A.
AU  - 
VL  - 388
UR  - 
DO  - 10.1515/BC.2007.114
AB  - In selenocysteine (Sec, U)-containing proteins the selenenylsulfide bridge and its reduced thiol-selenol counterpart are usually the significant species. An important role for serine as flanking amino acid in the redox potential of S-S and S-Se bridges was proposed for some thioredoxin reductases. To check the generality of this proposal, model tetrapeptides (GCCG, SCCG, GCCS, SCCS, GCUG, SCUG, GCUS, SCUS) were synthesized, including the GCUG sequence of human thioredoxin reductase. The influence on the redox potential of S-Se and S-S bridges as a function of pH and of serine at different positions reveals (i) a strong general pH dependence, and (ii) a significant influence of flanking serine on disulfide only at basic pH.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1821
TI  - Poppy alkaloid profiling by electrospray tandem mass spectrometry and electrospray FT-ICR mass spectrometry after [ring-13C6]-tyramine feeding
JO  - Phytochemistry
PY  - 2007
SP  - 189-202
AU  - Schmidt, J.
AU  - Boettcher, C.
AU  - Kuhnt, C.
AU  - Kutchan, T. M.
AU  - Zenk, M. H.
AU  - 
VL  - 68
UR  - 
DO  - 10.1016/j.phytochem.2006.10.003
AB  - Papaver alkaloids play a major role in medicine and pharmacy. In this study, [ring-13C6]-tyramine as a biogenetic precursor of these alkaloids was fed to Papaver somniferum seedlings. The alkaloid pattern was elucidated both by direct infusion high-resolution ESI-FT-ICR mass spectrometry and liquid chromatography/electrospray tandem mass spectrometry. Thus, based on this procedure, the structure of about 20 alkaloids displaying an incorporation of the labeled tyramine could be elucidated. These alkaloids belong to different classes, e.g. morphinan, benzylisoquinoline, protoberberine, benzo[c]phenanthridine, phthalide isoquinoline and protopine. The valuable information gained from the alkaloid profile demonstrates that the combination of these two spectrometric methods represents a powerful tool for evaluating biochemical pathways and facilitates the study of the flux of distant precursors into these natural products.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1817
TI  - Synthesis of Novel Steroid-Peptoid Hybrid Macrocycles by Multiple Multicomponent Macrocyclizations Including Bifunctional Building Blocks (MiBs)
JO  - Molecules
PY  - 2007
SP  - 1890-1899
AU  - Rivera, D.
AU  - Wessjohann, L.
AU  - 
VL  - 12
UR  - 
DO  - 10.3390/12081890
AB  - Two new groups of cholane-peptoid hybrid macrocycles were produced by implementing novel combinations of the MiB methodology. Steroid-based hybrid macrolactams including heterocycle and aryl moieties were obtained by utilizing cholanic dicarboxylic acids and diamines in a bidirectional double Ugi-Four-Component (Ugi-4CR) based macrocyclization protocol. Alternatively, N-substituted cyclocholamides were produced from a cholanic pseudo-amino acid by an Ugi-4CR-based cyclooligomerization approach. Both types of macrocycles are steroid-peptoid hybrid macrocycles containing exocyclic peptidic chains. These novel frameworks are a result of the use of bile acids bifunctionalized with carboxylic and amino functionalities as bifunctional building blocks of the Ugi-MiB approach.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1816
TI  - Studies on the regioselectivity of the Baeyer-Villiger reaction of 3-keto steroids: Conformational effects determine the migration aptitude
JO  - Steroids
PY  - 2007
SP  - 466-473
AU  - Rivera, D. G.
AU  - Pando, O.
AU  - Suardiaz, R.
AU  - Coll, F.
AU  - 
VL  - 72
UR  - 
DO  - 10.1016/j.steroids.2007.01.002
AB  - A detailed study of the Baeyer-Villiger reaction of 3-ketosteroids has been performed by using m-chloroperoxybenzoic and trifluoroperoxyacetic acids as oxidants. The process was fully regiospecific for 3-keto-5α-steroids with the employ of both peracids, and only partially regioselective for 3-keto-5β-steroids by using trifluoroperoxyacetic acid. Interestingly, the reaction resulted completely unselective for 3-keto-5β-steroids by using m-chloroperoxybenzoic acid. Theoretical studies were performed to explain the regiochemistry of this process, which is suggested to be controlled by conformational effects in the transition state of the Criegee rearrangement.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1815
TI  - Combinatorial Synthesis of Macrocycles by Multiple Multicomponent Macrocyclization Including Bifunctional Building Blocks (MiB)
JO  - Synlett
PY  - 2007
SP  - 0308-0312
AU  - Rivera, D.
AU  - Vercillo, O.
AU  - Wessjohann, L.
AU  - 
VL  - 2007
UR  - 
DO  - 10.1055/s-2007-968006
AB  - Small libraries of peptoid-based macro(multi)cycles were produced by applying combinatorial principles to the MiB methodology. This combinatorial approach features the incorporation of varied building blocks into the resulting macrocycles by mixing all the components in the same reaction pot. Both skeletal and appendage diversity could be generated in one shot due to the multicomponent nature of the system. HPLC and ESI-MS analyses showed a well-distributed composition of the libraries and revealed the presence of all possible macrocycles resulting from the different combinations of building blocks, especially of members with differentially substituted bridges not available by any other one-pot ­approach.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1841
TI  - Selenium in chemistry and biochemistry in comparison to sulfur
JO  - Biol. Chem.
PY  - 2007
SP  - 997-1006
AU  - Wessjohann, L. A.
AU  - Schneider, A.
AU  - Abbas, M.
AU  - Brandt, W.
AU  - 
VL  - 388
UR  - 
DO  - 10.1515/BC.2007.138
AB  - What makes selenoenzymes – seen from a chemist&#39;s view – so special that they cannot be substituted by just more analogous or adapted sulfur proteins? This review compiles and compares physicochemical properties of selenium and sulfur, synthetic routes to selenocysteine (Sec) and its peptides, and comparative studies of relevant thiols and selenols and their (mixed) dichalcogens, required to understand the special role of selenium in selenoproteins on the atomic molecular level. The biochemically most relevant differences are the higher polarizability of Se- and the lower pKa of SeH. The latter has a strikingly different pH-dependence than thiols, with selenols being active at much lower pH. Finally, selected typical enzymatic mechanisms which involve selenocysteine are critically discussed, also in view of the authors&#39; own results.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1840
TI  - Freezing Imine Exchange in Dynamic Combinatorial Libraries with Ugi Reactions: Versatile Access to Templated Macrocycles
JO  - Org. Lett.
PY  - 2007
SP  - 4733-4736
AU  - Wessjohann, L. A.
AU  - Rivera, D. G.
AU  - León, F.
AU  - 
VL  - 9
UR  - 
DO  - 10.1021/ol7021033
AB  - A novel approach to freeze the imine exchange process in dynamic combinatorial libraries by Ugi reactions was developed. Macrocyclic oligoimine libraries previously formed and altered by addition of metal templates are efficiently quenched by multiple multicomponent reactions. The approach may be considered as an alternative to the typical reduction with borohydrides and delivers polyazamacrocycles with variable side arms. High dilution is not required to achieve high yields.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 114
TI  - Bayesian Folding-In with Dirichlet Kernels for PLSI
T2  - Seventh IEEE International Conference on Data Mining (ICDM 2007)
PB  - 
PY  - 2007
SP  - 
AU  - Hinneburg, A.
AU  - Gabriel, H.-H.
AU  - Gohr, A.
AU  - 
VL  - 
UR  - 
DO  - 10.1109/ICDM.2007.15
AB  - Probabilistic latent semantic indexing (PLSI) represents documents of a collection as mixture proportions of latent topics, which are learned from the collection by an expectation maximization (EM) algorithm. New documents or queries need to be folded into the latent topic space by a simplified version of the EM-algorithm. During PLSI- Folding-in of a new document, the topic mixtures of the known documents are ignored. This may lead to a suboptimal model of the extended collection. Our new approach incorporates the topic mixtures of the known documents in a Bayesian way during folding- in. That knowledge is modeled as prior distribution over the topic simplex using a kernel density estimate of Dirichlet kernels. We demonstrate the advantages of the new Bayesian folding-in using real text data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 113
TI  - An Evaluation of Text Retrieval Methods for Similarity Search of Multi-dimensional NMR-Spectra
T2  - Bioinformatics Research and Development. BIRD 2007
PB  - Lecture Notes in Computer Science
PY  - 2007
SP  - 424-438
AU  - Hinneburg, A.
AU  - Porzel, A.
AU  - Wolfram, K.
AU  - 
VL  - 4414
UR  - 
SN  - 978-3-540-71233-6
DO  - 10.1007/978-3-540-71233-6_33
AB  - Searching and mining nuclear magnetic resonance (NMR)-spectra of naturally occurring substances is an important task to investigate new potentially useful chemical compounds. Multi-dimensional NMR-spectra are relational objects like documents, but consists of continuous multi-dimensional points called peaks instead of words. We develop several mappings from continuous NMR-spectra to discrete text-like data. With the help of those mappings any text retrieval method can be applied. We evaluate the performance of two retrieval methods, namely the standard vector space model and probabilistic latent semantic indexing (PLSI). PLSI learns hidden topics in the data, which is in case of 2D-NMR data interesting in its owns rights. Additionally, we develop and evaluate a simple direct similarity function, which can detect duplicates of NMR-spectra. Our experiments show that the vector space model as well as PLSI, which are both designed for text data created by humans, can effectively handle the mapped NMR-data originating from natural products. Additionally, PLSI is able to find meaningful ”topics” in the NMR-data.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1907
TI  - Structure determinants and substrate recognition of serine carboxypeptidase-like acyltransferases from plant secondary metabolism
JO  - FEBS Lett.
PY  - 2006
SP  - 6366-6374
AU  - Stehle, F.
AU  - Brandt, W.
AU  - Milkowski, C.
AU  - Strack, D.
AU  - 
VL  - 580
UR  - 
DO  - 10.1016/j.febslet.2006.10.046
AB  - Structures of the serine carboxypeptidase‐like enzymes 1‐O ‐sinapoyl‐β‐glucose:l ‐malate sinapoyltransferase (SMT) and 1‐O ‐sinapoyl‐β‐glucose:choline sinapoyltransferase (SCT) were modeled to gain insight into determinants of specificity and substrate recognition. The structures reveal the α/β‐hydrolase fold as scaffold for the catalytic triad Ser‐His‐Asp. The recombinant mutants of SMT Ser173Ala and His411Ala were inactive, whereas Asp358Ala displayed residual activity of 20%. 1‐O ‐sinapoyl‐β‐glucose recognition is mediated by a network of hydrogen bonds. The glucose moiety is recognized by a hydrogen bond network including Trp71, Asn73, Glu87 and Asp172. The conserved Asp172 at the sequence position preceding the catalytic serine meets sterical requirements for the glucose moiety. The mutant Asn73Ala with a residual activity of 13% underscores the importance of the intact hydrogen bond network. Arg322 is of key importance by hydrogen bonding of 1‐O ‐sinapoyl‐β‐glucose and l ‐malate. By conformational change, Arg322 transfers l ‐malate to a position favoring its activation by His411. Accordingly, the mutant Arg322Glu showed 1% residual activity. Glu215 and Arg219 establish hydrogen bonds with the sinapoyl moiety. The backbone amide hydrogens of Gly75 and Tyr174 were shown to form the oxyanion hole, stabilizing the transition state. SCT reveals also the catalytic triad and a hydrogen bond network for 1‐O ‐sinapoyl‐β‐glucose recognition, but Glu274, Glu447, Thr445 and Cys281 are crucial for positioning of choline.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1904
TI  - Chromogenic Meroterpenoids from the Mushrooms Russula ochroleuca and R. viscida
JO  - Eur. J. Org. Chem.
PY  - 2006
SP  - 1023-1033
AU  - Sontag, B.
AU  - Rüth, M.
AU  - Spiteller, P.
AU  - Arnold, N.
AU  - Steglich, W.
AU  - Reichert, M.
AU  - Bringmann, G.
AU  - 
VL  - 2006
UR  - 
DO  - 10.1002/ejoc.200500714
AB  - The spirodioxolactone ochroleucin A1 (1 ) is responsible for the red colour produced when the stalk base of Russula ochroleuca  and R. viscida  is treated with aqueous KOH. The labile chromogen rearranges easily into the isomeric dilactoneochroleucin A2 (2 ). Ochroleucin A1 is accompanied by the biosynthetically related hemiacetal ochroleucin B (5 ). The new compounds, whose structures were established by MS and NMR methods, appear to be derived biosynthetically by oxidative condensation of two monomeric units. One of them, 2,5‐dihydroxy‐4‐(3‐methylbut‐3‐en‐1‐ynyl)benzaldehyde (6 ), was detected in the crude toadstool extract by GC/MS comparison with a synthetic sample. The absolute configurations of the ochroleucins A1 and B have been determined by quantum chemical calculation of their CD spectra.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1902
TI  - Enantiomeric N-methyl-4-piperidyl benzilates as muscarinic receptor ligands: Radioligand binding studies and docking studies to models of the three muscarinic receptors M1, M2 and M3
JO  - Bioorg. Med. Chem.
PY  - 2006
SP  - 1729-1736
AU  - Selent, J.
AU  - Brandt, W.
AU  - Pamperin, D.
AU  - Göber, B.
AU  - 
VL  - 14
UR  - 
DO  - 10.1016/j.bmc.2005.10.030
AB  - Benzilic ester derivatives with a basic moiety like N-methyl-4-piperidyl benzilates are potential drugs for the treatment of urinary incontinence, duodenal and gastric ulcers and Parkinson’s disease. The effect of structural variations of chiral N-methyl-4-piperidyl benzilates was investigated using radioligand binding studies on muscarinic receptors (M1–M3). The results of the binding studies demonstrate that the absolute configuration and the aromatic substituent of benzilates have an influence on muscarinic affinity and selectivity. In this regard, (S)-configuration of benzilates and hydrophilic aromatic substituents seems to enhance muscarinic affinity. A model of the receptor ligand complex for N-methyl-4-piperidyl benzilates was obtained by molecular modelling. Both the affinity of enantiomeric benzilic esters and the subtype selectivity for muscarinic receptors are comprehensively explained by this model.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1901
TI  - Stereoselective synthesis of Boc-protected L-seleno- and tellurolanthionine, L-seleno- and tellurocystine and derivatives
JO  - Tetrahedron Lett.
PY  - 2006
SP  - 1019-1021
AU  - Schneider, A.
AU  - Rodrigues, O. E.
AU  - Paixão, M. W.
AU  - Appelt, H. R.
AU  - Braga, A. L.
AU  - Wessjohann, L. A.
AU  - 
VL  - 47
UR  - 
DO  - 10.1016/j.tetlet.2005.11.101
AB  - Optically active seleno- and telluro amino acids can be synthesized from serine via its β-lactone with selenides and tellurides under overall retention of the serine stereochemistry. Boc-protected l-selenolanthionine, l-tellurolanthionine, l-selenocystine, l-tellurocystine and l-tellurocysteine derivatives can be obtained in good yields.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1900
TI  - Flavonols and an indole alkaloid skeleton bearing identical acylated glycosidic groups from yellow petals of Papaver nudicaule
JO  - Phytochemistry
PY  - 2006
SP  - 191-201
AU  - Schliemann, W.
AU  - Schneider, B.
AU  - Wray, V.
AU  - Schmidt, J.
AU  - Nimtz, M.
AU  - Porzel, A.
AU  - Böhm, H.
AU  - 
VL  - 67
UR  - 
DO  - 10.1016/j.phytochem.2005.11.002
AB  - From yellow petals of Iceland poppy, besides the known flavonoid gossypitrin, seven kaempferol derivatives were isolated. In addition to kaempferol 3-O-β-sophoroside and kaempferol 3-O-β-sophoroside-7-O-β-glucoside, known from other plants, the mono- and dimalonyl conjugates of the latter were identified by MS and NMR spectroscopy. Structure analyses of a set of co-occurring pigments, the nudicaulins, revealed that they have the identical acylated glycoside moieties attached to a pentacyclic indole alkaloid skeleton for which the structure of 19-(4-hydroxyphenyl)-10H-1,10-ethenochromeno[2,3-b]indole-6,8,18-triol was deduced from MS and NMR as well as chemical and chiroptical methods.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1899
TI  - Erratum to “Accumulation of apocarotenoids in mycorrhizal roots of Ornithogalum umbellatum” [Phytochem. 67 (2006) 1196–1205]
JO  - Phytochemistry
PY  - 2006
SP  - 2090
AU  - Schliemann, W.
AU  - Schmidt, J.
AU  - Nimtz, M.
AU  - Wray, V.
AU  - Fester, T.
AU  - Strack, D.
AU  - 
VL  - 67
UR  - 
DO  - 10.1016/j.phytochem.2006.07.018
AB  - 
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1898
TI  - Accumulation of apocarotenoids in mycorrhizal roots of Ornithogalum umbellatum
JO  - Phytochemistry
PY  - 2006
SP  - 1196-1205
AU  - Schliemann, W.
AU  - Schmidt, J.
AU  - Nimtz, M.
AU  - Wray, V.
AU  - Fester, T.
AU  - Strack, D.
AU  - 
VL  - 67
UR  - 
DO  - 10.1016/j.phytochem.2006.05.005
AB  - Colonization of roots of Ornithogalum umbellatum by the arbuscular mycorrhizal fungus Glomus intraradices induced the accumulation of different types of apocarotenoids. In addition to the mycorrhiza-specific occurrence of cyclohexenone derivatives and the “yellow pigment” described earlier, free mycorradicin and numerous mycorradicin derivatives were detected in a complex apocarotenoid mixture for the first time. From the accumulation pattern of the mycorradicin derivatives their possible integration into the continuously accumulating “yellow pigment” is suggested. Structure analyses of the cyclohexenone derivatives by MS and NMR revealed that they are mono-, di- and branched triglycosides of blumenol C, 13-hydroxyblumenol C, and 13-nor-5-carboxy-blumenol C, some of which contain terminal rhamnose as sugar moiety.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1894
TI  - Supramolecular Compounds from Multiple Ugi Multicomponent Macrocyclizations: Peptoid-based Cryptands, Cages, and Cryptophanes
JO  - J. Am. Chem. Soc.
PY  - 2006
SP  - 7122-7123
AU  - Rivera, D. G.
AU  - Wessjohann, L. A.
AU  - 
VL  - 128
UR  - 
DO  - 10.1021/ja060720r
AB  - The first 3-fold multicomponent macrocyclizations of trifunctional building blocks were developed to produce, in one pot, cryptands, cages, and cryptophanes with peptoid tethers carrying additional recognition motifs. The straightforward, efficient, and diversity-oriented fashion by which these complex macromulticycles are obtained is suitable for building combinatorial libraries of synthetic receptors with potential applicability in catalysis and supramolecular and coordination chemistry. The strategy also easily allows creation of asymmetric macromulticyclic cavities, with up to 20 new bonds formed in one pot.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1893
TI  - cDNA sequences, MALDI-TOF analyses, and molecular modelling of barley PR-5 proteins
JO  - Phytochemistry
PY  - 2006
SP  - 1856-1864
AU  - Reiss, E.
AU  - Schlesier, B.
AU  - Brandt, W.
AU  - 
VL  - 67
UR  - 
DO  - 10.1016/j.phytochem.2006.06.014
AB  - Barley plants are known to produce various PR-5 proteins. Transcripts encoding eight different barley PR-5 proteins (TLPs 1–8, TLP for thaumatin-like protein) were identified and cloned – seven from infected leaves and one from developing grains. Here, we describe the cDNA sequences of four of these TLP isoforms. Moreover, the TLPs from the infected leaves (TLPs 1, 2, and TLPs 4–8) were subjected to MALDI-TOF mass spectrometric measurements that resulted in protein fragments consistent with their deduced peptide sequences. Multiple sequence alignment analysis revealed that the TLPs in barley fall into two groups: long-chain proteins (TLPs 5–8) having 16 cysteine residues and short-chain proteins (TLPs 1–4) with only 10 cysteine residues. Finally, modelling experiments highlighted the effects of sequence differences between the TLP isoforms in terms of their secondary structures and their molecular electrostatic potentials. We propose that these sequence differences have implications for the target preferences of the different isomers.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1890
TI  - Synthesis and Biological Evaluation of Spirostanes Including Butyrolactone Moieties
JO  - Lett. Org. Chem.
PY  - 2006
SP  - 519-522
AU  - Perez, C.
AU  - Leliebre-Lara, V.
AU  - Concepción, O.
AU  - Coll, F.
AU  - Rivera, D.
AU  - Pando, O.
AU  - 
VL  - 3
UR  - 
DO  - 10.2174/157017806778341870
AB  - Four new spirostanes functionalized with the butyrolactone moiety were efficiently synthesized and submitted to preliminary biological tests. Two practical synthetic routes were designed to enable the incorporation of the γ-lactone functionality into rings A and B. Butyrolactones 5 and 10 showed a promising plant growth-promoting activity which renders them good candidates for further biological studies.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1887
TI  - Analysis of fungal cyclopentenone derivatives from Hygrophorus spp. by liquid chromatography/electrospray-tandem mass spectrometry
JO  - J. Mass Spectrom.
PY  - 2006
SP  - 361-371
AU  - Lübken, T.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - Böttcher, C.
AU  - Schmidt, J.
AU  - 
VL  - 41
UR  - 
DO  - 10.1002/jms.996
AB  - Fruitbodies of the genus Hygrophorus  (Basidiomycetes) contain a series of anti‐biologically active compounds. These substances named hygrophorones possess a cyclopentenone skeleton. LC/ESI‐MS/MS presents a valuable tool for the identification of such compounds. The mass spectral behaviour of typical selected members of this group under positive and negative ion electrospray conditions is discussed. Using the ESI collision‐induced dissociation (CID) mass spectra of the [M + H]+ and [M − H]− ions, respectively, the compounds can be classified with respect to the substitution pattern at the cyclopentenone ring and the type of oxygenation at C‐6 (hydroxy/acetoxy or oxo function) of the side chain. The elemental composition of the fragment ions was determined by ESI‐QqTOF measurements. Thus, in case of the negative ion CID mass spectra an unusual loss of CO2 from the deprotonated molecular ions could be observed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1885
TI  - First enantiospecific Baker–Venkataraman-rearrangements aiming at the total synthesis of chiral anthrapyran antibiotics
JO  - Tetrahedron: Asymmetry
PY  - 2006
SP  - 3051-3057
AU  - Krohn, K.
AU  - Vidal, A.
AU  - Vitz, J.
AU  - Westermann, B.
AU  - Abbas, M.
AU  - Green, I.
AU  - 
VL  - 17
UR  - 
DO  - 10.1016/j.tetasy.2006.11.017
AB  - The base-catalyzed acyl transfer (Baker–Venkataraman reaction) of chiral 2-acetyl-1-hydroxyanthraquionone esters 6 of 2-methylbutanoic acid or 11 of O-allyl lactic acid proceeds with virtually no racemization to ketides 7 and 12. The subsequent acid-catalyzed cyclization to the chiral anthra[1,2-b]pyran antibiotics such as (S)-1″-11-dideoxyespicufolin 8 or 13 also occurs with a very low racemization.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1884
TI  - Dye-Modified and Photoswitchable Macrocycles by Multiple Multicomponent Macrocyclizations Including Bifunctional Building Blocks (MiBs)
JO  - QSAR Comb. Sci.
PY  - 2006
SP  - 461-464
AU  - Kreye, O.
AU  - Westermann, B.
AU  - Rivera, D.
AU  - Johnson, D.
AU  - Orru, R.
AU  - Wessjohann, L.
AU  - 
VL  - 25
UR  - 
DO  - 10.1002/qsar.200540217
AB  - The m ultiple m ulticomponent m acrocyclization i ncluding b ifunctional b uilding b locks (MiB) strategy is suitable to obtain macrocycles with inherent dye or photoswitchable subunits. Provided as dicarboxylic components in Ugi‐MiBs, these functional subunits can be combined with natural like biarylether and peptoid moieties.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1879
TI  - Phenolische Verbindungen einiger Flechten aus der Familie Physciaceae
JO  - Herzogia
PY  - 2006
SP  - 199-203
AU  - Huneck, S.
AU  - Schmidt, J.
AU  - 
VL  - 19
UR  - https://herzogia.blam-bl.de/herzogia/herzogia-downloads/herzogia-downloads-19-2006.html
AB  - The following lichen substances were detected in six species of Physciaceae by HPLC-ESI-MS/MS: Phaeophyscia orbicularis: atranorin (1), methyl ß-orcinolcarboxylate (6), Physcia adscendens: 1, 6, chloroatranorin (2), 5-hydroxyatranorin (3, new), norbaeomycesic acid (4), 3&#39;-demethylatranorin (5, new), Physcia aipolia: 1, 2, 3, 4, 5 and 6, Physcia caesia: 1, 4 and 5, Physcia stellaris: 1, 2, 4, 5 and 6, Physcia tenella: 1, 2, 4, 5 and 6.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1878
TI  - Lydiamycins A–D: Cyclodepsipetides with Antimycobacterial Properties
JO  - Angew. Chem. Int. Ed.
PY  - 2006
SP  - 3067-3072
AU  - Huang, X.
AU  - Roemer, E.
AU  - Sattler, I.
AU  - Moellmann, U.
AU  - Christner, A.
AU  - Grabley, S.
AU  - 
VL  - 45
UR  - 
DO  - 10.1002/anie.200503381
AB  - Four new antibiotics were isolated from a fermentation broth of Steptomyces lydicus  (strain HKI0343). The 13‐membered‐ring peptides (see formula, XY: CH2NH, CHNH; R1, R2: H, OH) are cyclized through a lactone function at serine and also contain the nonproteinogenic amino acid piperazic acid (or a derivative thereof). The peptides show promising activity against various mycobacteria without being cytotoxic.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1877
TI  - Lydiamycine A–D: Cyclodepsipeptide mit antimykobakteriellen Eigenschaften
JO  - Angew. Chem.
PY  - 2006
SP  - 3138-3143
AU  - Huang, X.
AU  - Roemer, E.
AU  - Sattler, I.
AU  - Moellmann, U.
AU  - Christner, A.
AU  - Grabley, S.
AU  - 
VL  - 118
UR  - 
DO  - 10.1002/ange.200503381
AB  - Vier neue Antibiotika wurden aus Streptomyces lydicus  (Stamm HKI0343) isoliert. Die 13‐gliedrigen Peptidringe (siehe Bild; X‐Y=CH2‐NH, CHNH; R1, R2=H, OH) sind über ein Serin zum Lacton cyclisiert und bestehen aus L ‐Alanin, D ‐Leucin, L ‐Serin und der nichtproteinogenen Aminosäure Piperazinsäure oder ihren Derivaten. Die Naturstoffe zeigen eine vielversprechende Wirkung gegen unterschiedliche Mykobakterien, ohne dabei toxisch zu sein.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1876
TI  - Differential distribution of tocopherols and tocotrienols in photosynthetic and non-photosynthetic tissues
JO  - Phytochemistry
PY  - 2006
SP  - 1185-1195
AU  - Horvath, G.
AU  - Wessjohann, L.
AU  - Bigirimana, J.
AU  - Jansen, M.
AU  - Guisez, Y.
AU  - Caubergs, R.
AU  - Horemans, N.
AU  - 
VL  - 67
UR  - 
DO  - 10.1016/j.phytochem.2006.04.004
AB  - Tocopherols and tocotrienols are vitamin E compounds, differing only in the saturation state of the isoprenoid side chain. Tocopherol biosynthesis, physiology and distribution have been studied in detail. Tocopherols have been found in many different plant species, and plant tissues. In contrast, comparatively little is known about the physiology and distribution of tocotrienols. These compounds appear to be considerably less widespread in the plant kingdom. In this study 80 different plant species were analysed for the presence of tocotrienols. Twenty-four species were found to contain significant amounts of tocotrienols. No taxonomic relation was apparent among the 16 dicotyledonous species that were found to contain tocotrienol. Monocotyledonous species (eight species) belonged either to the Poaceae (six species) or the Aracaceae (two species).A more detailed analysis of tocotrienol accumulation revealed the presence of tocotrienols in several non-photosynthetic tissues and organs, i.e. seeds, fruits and in latex, in concentrations up to 2000 ppm. No tocotrienols could be detected in mature photosynthetic tissues. However, we found the transient accumulation of low levels of tocotrienols in the young coleoptiles of plant species whose seeds contained tocotrienols. No measurable tocotrienol biosynthesis was apparent in coleoptiles, or in chloroplasts isolated from such coleoptiles. In line with these results, we found that tocotrienol accumulation in coleoptiles was not associated with chloroplasts. Based on our data, we conclude that tocotrienols may be transiently present in photosynthetically active tissues, however, it remains to be proven whether the tocotrienols are biosynthesised in such tissues, or imported from elsewhere in the plant.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1875
TI  - Accumulation of tocopherols and tocotrienols during seed development of grape (Vitis vinifera L. cv. Albert Lavallée)
JO  - Plant Physiol. Biochem.
PY  - 2006
SP  - 724-731
AU  - Horvath, G.
AU  - Wessjohann, L.
AU  - Bigirimana, J.
AU  - Monica, H.
AU  - Jansen, M.
AU  - Guisez, Y.
AU  - Caubergs, R.
AU  - Horemans, N.
AU  - 
VL  - 44
UR  - 
DO  - 10.1016/j.plaphy.2006.10.010
AB  - Tocopherols and tocotrienols are present in mature seeds. Yet, little is known about the physiological role and the metabolism of these compounds during seed development. Here we present data on tocopherol and tocotrienol accumulation during seed development in Vitis vinifera L. cv. Albert Lavallée (Royal). This species was chosen for its ability to synthesize both tocopherols and tocotrienols. It is shown here for the first time that during seed development there are significant differences in localization and accumulation kinetics of tocopherols and tocotrienols. Tocopherols are found homogeneously dispersed throughout all tissues of the seed, in concentrations ranging from 20 to 100 μg tocopherol per g dry weight. Tocopherol levels decrease gradually during seed development. In contrast, tocotrienols are only found in the endosperm of the seeds, accumulating in a sigmoid fashion during the maturation period of seed development. Tocotrienol levels were found to be (54 ± 7.4) μg/g dry seed in 90-day-old seeds of V. vinifera L. Furthermore, tocotrienol biosynthesis is demonstrated in these seeds during tocotrienol accumulation and in an endosperm fraction isolated at 75 days after flowering.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1927
TI  - Comparative transcript and alkaloid profiling in Papaver species identifies a short chain dehydrogenase/reductase involved in morphine biosynthesis
JO  - Plant J.
PY  - 2006
SP  - 177-192
AU  - Ziegler, J.
AU  - Voigtländer, S.
AU  - Schmidt, J.
AU  - Kramell, R.
AU  - Miersch, O.
AU  - Ammer, C.
AU  - Gesell, A.
AU  - Kutchan, T. M.
AU  - 
VL  - 48
UR  - 
DO  - 10.1111/j.1365-313X.2006.02860.x
AB  - Plants of the order Ranunculales, especially members of the species Papaver , accumulate a large variety of benzylisoquinoline alkaloids with about 2500 structures, but only the opium poppy (Papaver somniferum ) and Papaver setigerum  are able to produce the analgesic and narcotic morphine and the antitussive codeine. In this study, we investigated the molecular basis for this exceptional biosynthetic capability by comparison of alkaloid profiles with gene expression profiles between 16 different Papaver  species. Out of 2000 expressed sequence tags obtained from P. somniferum , 69 show increased expression in morphinan alkaloid‐containing species. One of these cDNAs, exhibiting an expression pattern very similar to previously isolated cDNAs coding for enzymes in benzylisoquinoline biosynthesis, showed the highest amino acid identity to reductases in menthol biosynthesis. After overexpression, the protein encoded by this cDNA reduced the keto group of salutaridine yielding salutaridinol, an intermediate in morphine biosynthesis. The stereoisomer 7‐epi ‐salutaridinol was not formed. Based on its similarities to a previously purified protein from P. somniferum  with respect to the high substrate specificity, molecular mass and kinetic data, the recombinant protein was identified as salutaridine reductase (SalR; EC 1.1.1.248). Unlike codeinone reductase, an enzyme acting later in the pathway that catalyses the reduction of a keto group and which belongs to the family of the aldo‐keto reductases, the cDNA identified in this study as SalR belongs to the family of short chain dehydrogenases/reductases and is related to reductases in monoterpene metabolism.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology; Molecular Signal Processing
ER  - 


TY  - JOUR
ID  - 1926
TI  - Regiospecific Synthesis of 4-Alkoxy and 4-Amino Substituted 2-Trifluoromethyl Pyrroles
JO  - J. Org. Chem.
PY  - 2006
SP  - 6996-6998
AU  - Zanatta, N.
AU  - Schneider, J. M. F. M.
AU  - Schneider, P. H.
AU  - Wouters, A. D.
AU  - Bonacorso, H. G.
AU  - Martins, M. A. P.
AU  - Wessjohann, L. A.
AU  - 
VL  - 71
UR  - 
DO  - 10.1021/jo061058k
AB  - A simple and regiospecific synthesis of 4-alkoxy(amino)-2-trifluoromethyl pyrroles from 5-azido-4-alkoxy(amino)-1,1,1-trifluoro-pent-3-en-2-ones by an aza-Wittig cyclization of aminophosphoranes is described. The structures of the pyrroles and their synthetic intermediates were supported by NMR and HRMS analysis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1925
TI  - Constitutive Accumulation of cis-piceid in Transgenic Arabidopsis Overexpressing a Sorghum Stilbene Synthase Gene
JO  - Plant Cell Physiol.
PY  - 2006
SP  - 1017-1021
AU  - Yu, C. K. Y.
AU  - Lam, C. N. W.
AU  - Springob, K.
AU  - Schmidt, J.
AU  - Chu, I. K.
AU  - Lo, C.
AU  - 
VL  - 47
UR  - 
DO  - 10.1093/pcp/pcj061
AB  - Sorghum SbSTS1 was the first example of a stilbene synthase gene in monocots. Previously, we demonstrated that the gene was involved in defense responses. To examine its biochemical function in planta, SbSTS1 was overexpressed in transgenic Arabidopsis. Metabolite analysis revealed that cis -resveratrol glucoside (piceid) accumulated as the major stilbene in the transgenic lines. Using liquid chromatography–tandem mass spectrometry (LC–MS/MS) in selected reaction monitoring mode, up to 580 μg g −1 FW of cis -piceid were detected in 2-week-old plants, which represent a convenient source of the cis -isomers for pharmacological investigations. Our results also suggested the presence of unknown stilbene isomerase activities in Arabidopsis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1923
TI  - An efficient synthesis of the phytoestrogen 8-prenylnaringenin from xanthohumol by a novel demethylation process
JO  - Tetrahedron
PY  - 2006
SP  - 6961-6966
AU  - Wilhelm, H.
AU  - Wessjohann, L. A.
AU  - 
VL  - 62
UR  - 
DO  - 10.1016/j.tet.2006.04.060
AB  - 8-Prenylnaringenin, a flavonoid, is the strongest known phytoestrogen (plant derived estrogen mimic) used in phytomedicinal applications. Starting from xanthohumol a byproduct of hops-extraction, 8-prenylnaringenin can be synthesized via isoxanthohumol. Of various demethylation procedures tested, the best yield (92%) is obtained by treatment with scandium trifluoromethanesulfonate and potassium iodide without any need of protection. The demethylation with AlBr3/collidine and of the TIPS protected isoxanthohumol provides good results too.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1922
TI  - Synthesis of Steroid−Biaryl Ether Hybrid Macrocycles with High Skeletal and Side Chain Variability by Multiple Multicomponent Macrocyclization Including Bifunctional Building Blocks
JO  - J. Org. Chem.
PY  - 2006
SP  - 7521-7526
AU  - Wessjohann, L. A.
AU  - Rivera, D. G.
AU  - Coll, F.
AU  - 
VL  - 71
UR  - 
DO  - 10.1021/jo0608570
AB  - Utilizing the multiple multicomponent macrocyclization including bifunctional building blocks (MiB) strategy, a library of nonracemic, nonrepetitive peptoid-containing steroid−biaryl ether hybrid macrocycles was built. Up to 16 new bonds, including those of the macrocyclization, can be formed in one pot simultaneously while introducing varied elements of diversity. Functional diversity is generated primarily by choosing Ugi-reactive functional building blocks, bearing the respective recognition or catalytic motifs. These appear attached to the peptoid backbone of the macrocyclic cavity, similar to side chains of amino acids found in enzyme active sites. Likewise, skeletal diversity is based on the variation of defined bifunctional building blocks which allow the parallel formation of macrocyclic cavities that are highly diverse in shape and size and thus perspectively in function. This straightforward approach is suitable to generate multifunctional macrocycles for applications in catalysis, supramolecular, or biological chemistry.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1921
TI  - Synthesis of Mechanistic Probes and Inhibitors for Prenylating Enzymes
JO  - Pol. J. Chem.
PY  - 2006
SP  - 673-678
AU  - Wessjohann, L. A.
AU  - Fulhorst, M.
AU  - Zakharova, S.
AU  - 
VL  - 80
UR  - http://ichf.edu.pl/pjch/pj-2006/pj-2006-04a.pdf
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1916
TI  - Synthesis and characterization of platinum(IV) complexes with N,S and S,S heterocyclic ligands
JO  - Inorg. Chim. Acta
PY  - 2006
SP  - 4326-4334
AU  - Vetter, C.
AU  - Wagner, C.
AU  - Schmidt, J.
AU  - Steinborn, D.
AU  - 
VL  - 359
UR  - 
DO  - 10.1016/j.ica.2006.06.007
AB  - The reactions of [PtMe3(OAc)(bpy)] (4) with the N,S and S,S containing heterocycles, pyrimidine-2-thione (pymtH), pyridine-2-thione (pytH), thiazoline-2-thione (tztH) and thiophene-2-thiol (tptH), resulted in the formation of the monomeric complexes [PtMe3(-κS)(bpy)] ( = pymt, 5; pyt, 6; tzt, 7; tpt, 8), where the heterocyclic ligand is coordinated via the exocyclic sulfur atom. In contrast, in the reactions of [PtMe3(OAc)(Me2CO)x] (3, x = 1 or 2) with pymtH, pytH, tztH and tptH dimeric complexes [{PtMe3(μ-)}2] (μ- = pymt, 9; pyt, 10; tzt, 11) and the tetrameric complex [{PtMe3(μ3-tpt-κS)}4] (12), respectively, were formed. The complexes were characterized by microanalyses, 1H and 13C NMR spectroscopy and negative ESI-MS (12) measurements. Single-crystal X-ray diffraction analysis of [PtMe3(pymt-κS)(bpy)] (5) exhibited a conformation where the pymt ligand lies nearly perpendicular to the complex plane above the bpy ligand that was also confirmed by quantum chemical calculations on the DFT level of theory.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1913
TI  - Quaternary protoberberine alkaloids from Stephania rotunda
JO  - Vietnam J. Chem.
PY  - 2006
SP  - 259-264
AU  - Thuy, T. T.
AU  - Franke, K.
AU  - Porzel, A.
AU  - Wessjohann, L.
AU  - Sung, T. V.
AU  - 
VL  - 44
UR  - http://vjs.ac.vn/index.php/vjchem/issue/view/376
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1912
TI  - Morphinane and oxoaporphine alkaloids from Stephania rotunda Lour
JO  - Vietnam J. Chem.
PY  - 2006
SP  - 110-114
AU  - Thuy, T. T.
AU  - Sung, T. V.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - 
VL  - 44
UR  - http://vjs.ac.vn/index.php/vjchem/issue/view/375
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1911
TI  - Isoquinolone and Protoberberine Alkaloids from Stephania rotunda
JO  - ChemInform
PY  - 2006
SP  - 
AU  - Thuy, T. T.
AU  - Porzel, A.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - Sung, T. V.
AU  - 
VL  - 37
UR  - 
DO  - 10.1002/chin.200601202
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1910
TI  - Benzyl isoquinoline and tetrahydroprotoberberine alkaloids from Stephania rotunda
JO  - Vietnam J. Chem.
PY  - 2006
SP  - 372-376
AU  - Thuy, T. T.
AU  - Sung, T. V.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - 
VL  - 44
UR  - http://vjs.ac.vn/index.php/vjchem/issue/view/377
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1909
TI  - Squalene and amentoflavone from Antidesma laciniatum
JO  - Bull. Chem. Soc. Ethiop.
PY  - 2006
SP  - 325-328
AU  - Tchinda, A. T.
AU  - Teshome, A.
AU  - Dagne, E.
AU  - Arnold, N.
AU  - Wessjohann, L. A.
AU  - 
VL  - 20
UR  - 
DO  - 10.4314/bcse.v20i2.61417
AB  - Squalene, (2E, 7x,11x)-phyt-2-en-1-ol and amentoflavone have been isolated from the extract of the leaves of Antidesma laciniatum. Their structures were elucidated using spectroscopic methods. This is the first report of these compounds from Antidesma species.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1867
TI  - Mutational Studies Confirm the Catalytic Triad in the Human Selenoenzyme Thioredoxin Reductase Predicted by Molecular Modeling
JO  - ChemBioChem
PY  - 2006
SP  - 1649-1652
AU  - Gromer, S.
AU  - Wessjohann, L. A.
AU  - Eubel, J.
AU  - Brandt, W.
AU  - 
VL  - 7
UR  - 
DO  - 10.1002/cbic.200600080
AB  - Site‐directed mutagenesis of Glu477 of the human thioredoxin reductase (see figure) to glutamine, alanine, or lysine led to a significant drop in enzymatic activity. This study reinforces previous theoretical calculations which suggested that a swapping catalytic triad exists in the active site of this enzyme.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1866
TI  - Lanthanum-catalyzed aqueous acylation of monosaccharides by benzoyl methyl phosphate
JO  - Can. J. Chem.
PY  - 2006
SP  - 620-624
AU  - Gray, I. J.
AU  - Ren, R.
AU  - Westermann, B.
AU  - Kluger, R.
AU  - 
VL  - 84
UR  - 
DO  - 10.1139/v06-047
AB  - It was previously reported that diols dissolved in water (pH 8, EPPS buffer) react with benzoyl methyl phosphate (BMP) in the presence of lanthanide ions to form monobenzoyl esters. We have investigated the possibility of extending this process to include formation of esters of monosaccharides in water from lanthanide-catalyzed reactions with BMP. The combination of methyl-α-D-glucopyranoside and BMP in the presence of lanthanum trichloride gave selective monoacylation of the 2- and 6-hydroxyl groups in a ratio of 2:1. The likely mechanism involves preferential bisbidentate coordination of BMP and the diol to lanthanide ion (which explains how an ester forms when water is in enormous excess) followed by base-catalyzed intramolecular acyl transfer. The method should be generally applicable where a selective acylation reaction in water as solvent is desirable. Key words: benzoyl methyl phosphate, lanthanide, catalysis, water, monoacylation, selective.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1864
TI  - 2″-O-Glucosylvitexin, a chemotaxonomic marker for the genus Cryptocoryne (Araceae)
JO  - Biochem. Syst. Ecol.
PY  - 2006
SP  - 546-548
AU  - Franke, K.
AU  - Hoffmann, M.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 34
UR  - 
DO  - 10.1016/j.bse.2005.10.017
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1862
TI  - Total Synthesis of Tubulysin U and V
JO  - Angew. Chem. Int. Ed.
PY  - 2006
SP  - 7235-7239
AU  - Dömling, A.
AU  - Beck, B.
AU  - Eichelberger, U.
AU  - Sakamuri, S.
AU  - Menon, S.
AU  - Chen, Q.-Z.
AU  - Lu, Y.
AU  - Wessjohann, L. A.
AU  - 
VL  - 45
UR  - 
DO  - 10.1002/anie.200601259
AB  - Tubulysins are among the most potent cytotoxic agents known. Now the first total synthesis of some members has been achieved by utilizing a rapid three‐component reaction for the synthesis of the unusual central thiazole amino acid tubuvaline (see scheme; Boc=tert ‐butoxycarbonyl, Ac=acetyl), thereby opening new perspectives for anticancer drug development.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1861
TI  - Total Synthesis of Tubulysin U and V
JO  - Angew. Chem.
PY  - 2006
SP  - 7393-7397
AU  - Dömling, A.
AU  - Beck, B.
AU  - Eichelberger, U.
AU  - Sakamuri, S.
AU  - Menon, S.
AU  - Chen, Q.-Z.
AU  - Lu, Y.
AU  - Wessjohann, L. A.
AU  - 
VL  - 118
UR  - 
DO  - 10.1002/ange.200601259
AB  - Tubulysine gehören zu den wirksamsten bekannten Zytostatika. Die erste Totalsynthese einiger Vertreter gelang mit einer schnellen Dreikomponenten‐Eintopfsynthese der ungewöhnlichen zentralen Thiazol‐Aminosäure Tubuvalin (siehe Schema; Boc=tert ‐Butoxycarbonyl, Ac=Acetyl) und eröffnet neue Perspektiven in der Anwendung als Wirkstoff.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1858
TI  - Rapid Combinatorial Access to Macrocyclic Ansapeptoids and Ansapeptides with Natural-Product-like Core Structures
JO  - Synthesis
PY  - 2006
SP  - 3997-4004
AU  - de Greef, M.
AU  - Abeln, S.
AU  - Belkasmi, K.
AU  - Dömling, A.
AU  - Orru, R.
AU  - Wessjohann, L.
AU  - 
VL  - 2006
UR  - 
DO  - 10.1055/s-2006-950335
AB  - 14-Membered ansa-cyclopeptide alkaloids are among the most abundant natural macrocycles and thus valuable templates for diversity-oriented synthesis with biological relevance. A rapid synthesis of the core structure is conceivable by a combination of an Ugi four-component reaction with bifunctional building blocks to form the dipeptoid part, followed by a suitable macrocyclization reaction. The latter step is crucial, and an uncommon macroetherification gave the best results. The use of ammonium salts allows direct access to peptides instead of peptoids. Depending on the substitution pattern, some cyclopeptoids show planar chirality despite free rotation of the phenylene group.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1857
TI  - Synthesis of N-(β-D-glucopyranosyl) monoamides of dicarboxylic acids as potential inhibitors of glycogen phosphorylase
JO  - Carbohyd. Res.
PY  - 2006
SP  - 947-956
AU  - Czifrák, K.
AU  - Hadady, Z.
AU  - Docsa, T.
AU  - Gergely, P.
AU  - Schmidt, J.
AU  - Wessjohann, L.
AU  - Somsák, L.
AU  - 
VL  - 341
UR  - 
DO  - 10.1016/j.carres.2006.03.002
AB  - O-Peracetylated N-(β-d-glucopyranosyl)imino trimethylphosphorane obtained in situ from 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl azide and PMe3 was reacted with saturated and unsaturated aliphatic and aromatic dicarboxylic acids, or their anhydrides, or monoesters to give the corresponding N-(β-d-glucopyranosyl) monoamides of dicarboxylic acids or derivatives. The acetyl protecting groups were removed according to the Zemplén protocol to give a series of compounds which showed moderate inhibitory effects against rabbit muscle glycogen phosphorylase b. The best inhibitor was 3-(N-β-d-glucopyranosyl-carbamoyl)propanoic acid (7) with Ki = 20 μM.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1851
TI  - Microwave-Mediated Palladium-Catalyzed Asymmetric Allylic Alkylation Using Chiral β-Seleno Amides
JO  - Eur. J. Org. Chem.
PY  - 2006
SP  - 4993-4997
AU  - Braga, A. L.
AU  - Vargas, F.
AU  - Sehnem, J. A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 2006
UR  - 
DO  - 10.1002/ejoc.200600707
AB  - A class of enantiopure β‐seleno amide palladium complexes catalyze the microwave‐accelerated enantioselective allylic alkylation of rac ‐1,3‐diphenyl‐2‐propenyl acetate with different malonates. Good yields and enantiomeric excess values of up to 94 % ee  were obtained after irradiation times of 2 or 4 min.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1849
TI  - Biotransformation of 1-Naphthol by a Strictly Aquatic Fungus
JO  - Curr. Microbiol.
PY  - 2006
SP  - 216-220
AU  - Augustin, T.
AU  - Schlosser, D.
AU  - Baumbach, R.
AU  - Schmidt, J.
AU  - Grancharov, K.
AU  - Krauss, G.
AU  - Krauss, G.-J.
AU  - 
VL  - 52
UR  - 
DO  - 10.1007/s00284-005-0239-z
AB  - The aquatic hyphomycete Heliscus lugdunensis belongs to a group of exclusively aquatic mitosporic fungi with an only scarcely explored potential to oxidatively attack xenobiotic compounds, and was used to study the biotransformation of the environmental pollutant metabolite 1-naphthol. H. lugdunensis metabolized approximately 74% of 1-naphthol within 5 days. The identification and quantification of degradation products using gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, and high performance liquid chromatography revealed that approximately 12% of the parent compound was converted into 1-naphthylsulfate, 3% was transformed into 1-methoxy-naphthalene, and less than 1% was converted into 1,4-naphthoquinone. A further metabolite, most likely 4-hydroxy-1-naphthylsulfate, was also detected. In contrast to sulfate conjugate metabolites, no glucuronide and glucoside conjugates of 1-naphthol were found, and neither UDP-glucuronyltransferase nor UDP-glucosyltransferase present in H. lugdunensis showed activity towards 1-naphthol. These results support a role of fungi adapted to aquatic environments in affecting the environmental fate of pollutants in aquatic ecosystems.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1848
TI  - Chemical constituents of Zizyphus sativa Gaertn fruits. I - Alphitolic acid and its derivatives
JO  - Vietnam J. Chem.
PY  - 2006
SP  - 787-790
AU  - Anh, N. T. H.
AU  - Sung, T. V.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 44
UR  - http://vjs.ac.vn/index.php/vjchem/issue/view/380
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1847
TI  - One pot synthesis of selenocysteine containing peptoid libraries by Ugi multicomponent reactions in water
JO  - Chem. Commun.
PY  - 2006
SP  - 541-543
AU  - Abbas, M.
AU  - Bethke, J.
AU  - Wessjohann, L. A.
AU  - 
VL  - 2006
UR  - 
DO  - 10.1039/B514597J
AB  - Selenocysteine containing peptoids and peptide–peptoid conjugates were synthesized by combinatorial Ugi-MCRs (multicomponent reactions) in water: for the first time, an acetal (selenoacetal 2a) was used in Ugi-MCR to furnish selenocysteine peptoids in one step as model compounds for selenocysteinepeptides and proteins.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 128
TI  - Similarity Search for Multi-dimensional NMR-Spectra of Natural Products
T2  - Knowledge Discovery in Databases: PKDD 2006
PB  - Lecture Notes in Computer Science
PY  - 2006
SP  - 650-658
AU  - Wolfram, K.
AU  - Porzel, A.
AU  - Hinneburg, A.
AU  - 
VL  - 4213
UR  - 
SN  - 978-3-540-46048-0
DO  - 10.1007/11871637_67
AB  - Searching and mining nuclear magnetic resonance (NMR)-spectra of naturally occurring products is an important task to investigate new potentially useful chemical compounds. We develop a set-based similarity function, which, however, does not sufficiently capture more abstract aspects of similarity. NMR-spectra are like documents, but consists of continuous multi-dimensional points instead of words. Probabilistic semantic indexing (PLSI) is an retrieval method, which learns hidden topics. We develop several mappings from continuous NMR-spectra to discrete text-like data. The new mappings include redundancies into the discrete data, which proofs helpful for the PLSI-model used afterwards. Our experiments show that PLSI, which is designed for text data created by humans, can effectively handle the mapped NMR-data originating from natural products. Additionally, PLSI combined with the new mappings is able to find meaningful ”topics” in the NMR-data.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - CHAP
ID  - 127
TI  - Macrocyclic peptoids: N-alkylated cyclopeptides and depsipeptides
T2  - TARGETS IN HETEROCYCLIC SYSTEMS - Chemistry and Properties
PB  - Reviews and Accounts on Heterocyclic Chemistry
PY  - 2006
SP  - 24-53
AU  - Wessjohann, L. A.
AU  - Andrade, C. K. Z.
AU  - Vercillo, O. E.
AU  - Rivera, D. G.
AU  - 
VL  - 10
UR  - https://www.soc.chim.it/sites/default/files/ths/old/vol_10_2006.pdf
AB  - 
A2  - Attanasi, O. A. &amp; Spinelli, D., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 124
TI  - Naturstoffchemie: Mikrobielle, pflanzliche und tierische Naturstoffe
T2  - 
PB  - 
PY  - 2006
SP  - 
AU  - Nuhn, P.
AU  - Wessjohann, L. A.
AU  - 
VL  - 
UR  - 
AB  - "Naturstoffchemie" vermittelt Kenntnisse über die universellen Grundbausteine der Organismen (z.B. Aminosäuren, Peptide, Proteine etc.) über essenzielle biologisch aktive Verbindungen (z.B. Vitamine, Coenzyme, intrazelluläre Regulationsstoffe) über ausgewählte sekundäre Naturstoffe (z.B. Alkaloide, Antibiotika, isoprenoide Verbindungen). Insbesondere Naturstoffe und deren Abwandlungsprodukte mit bemerkenswerter biologischer Aktivität wurden bei der Auswahl berücksichtigt. Außerdemfinden sich die wichtigsten Synthese- und Abwandlungsmethoden typischer Vertreter. Struktur, chemische und physikochemische Eigenschaften sowie biologische Wirkungen wurden besonders herausgearbeitet.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1977
TI  - Three phthalide derivatives from Angelica sinensis Rhizomes
JO  - Vietnam J. Chem.
PY  - 2005
SP  - 119-122
AU  - Nguyen, T. H. V.
AU  - Nguyen, T. H. A.
AU  - Tran, V. S.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - 
VL  - 43
UR  - http://vjs.ac.vn/index.php/vjchem/article/view/1658
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1976
TI  - Studies on chemical composition of Angelica sinensis. Part VI - Angelicolide and three other compounds
JO  - Vietnam J. Chem.
PY  - 2005
SP  - 749-752
AU  - Nguyen, T. H. V.
AU  - Nguyen, T. H. A.
AU  - Tran, V. S.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - 
VL  - 43
UR  - http://vjs.ac.vn/index.php/vjchem/issue/view/374
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1975
TI  - Studies on chemical composition of Angelica sinensis&#39;s. V - The nitrogen-containing compounds
JO  - Vietnam J. Chem.
PY  - 2005
SP  - 605-609
AU  - Nguyen, T. H. V.
AU  - Nguyen, T. H. A.
AU  - Tran, V. S.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - 
VL  - 43
UR  - http://vjs.ac.vn/index.php/vjchem/issue/view/373
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1974
TI  - Four phthalides from the roots of Angelica sinensis
JO  - Vietnam J. Chem.
PY  - 2005
SP  - 228-231
AU  - Nguyen, T. H. V.
AU  - Nguyen, T. H. A.
AU  - Tran, V. S.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - 
VL  - 43
UR  - http://vjs.ac.vn/index.php/vjchem/issue/view/370
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1973
TI  - Chemical study of Angelica sinensis&#39;s roots
JO  - Vietnam J. Chem.
PY  - 2005
SP  - 494-498
AU  - Nguyen, T. H. V.
AU  - Nguyen, T. H. A.
AU  - Tran, V. S.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - 
VL  - 43
UR  - http://vjs.ac.vn/index.php/vjchem/issue/view/372
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1972
TI  - Antifungal compounds from the vietnamese plant Bousingonia Mekongense
JO  - Adv. Nat. Sci. (Vietnam)
PY  - 2005
SP  - 227-230
AU  - Nguyen, M. C.
AU  - Tran, Q. H.
AU  - Nguyen, Q. C.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 6
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1967
TI  - Pre- and Postinvasion Defenses Both Contribute to Nonhost Resistance in Arabidopsis
JO  - Science
PY  - 2005
SP  - 1180-1183
AU  - Lipka, V.
AU  - Dittgen, J.
AU  - Bednarek, P.
AU  - Bhat, R.
AU  - Wiermer, M.
AU  - Stein, M.
AU  - Landtag, J.
AU  - Brandt, W.
AU  - Rosahl, S.
AU  - Scheel, D.
AU  - Llorente, F.
AU  - Molina, A.
AU  - Parker, J.
AU  - Somerville, S.
AU  - Schulze-Lefert, P.
AU  - 
VL  - 310
UR  - 
DO  - 10.1126/science.1119409
AB  - Nonhost resistance describes the immunity of an entire plant species against nonadapted pathogen species. We report that Arabidopsis PEN2 restricts pathogen entry of two ascomycete powdery mildew fungi that in nature colonize grass and pea species. The PEN2 glycosyl hydrolase localizes to peroxisomes and acts as a component of an inducible preinvasion resistance mechanism. Postinvasion fungal growth is blocked by a separate resistance layer requiring the EDS1-PAD4-SAG101 signaling complex, which is known to function in basal and resistance (R) gene–triggered immunity. Concurrent impairment of pre- and postinvasion resistance renders Arabidopsis a host for both nonadapted fungi.
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions
ER  - 


TY  - JOUR
ID  - 1960
TI  - N-(Jasmonoyl)tyrosine-Derived Compounds from Flowers of Broad Beans (Vicia faba)
JO  - J. Nat. Prod.
PY  - 2005
SP  - 1345-1349
AU  - Kramell, R.
AU  - Schmidt, J.
AU  - Herrmann, G.
AU  - Schliemann, W.
AU  - 
VL  - 68
UR  - 
DO  - 10.1021/np0501482
AB  - Two new amide-linked conjugates of jasmonic acid, N-[(3R,7R)-(−)-jasmonoyl]-(S)-dopa (3) and N-[(3R,7R)-(−)-jasmonoyl]-dopamine (5), were isolated in addition to the known compound N-[(3R,7R)-(−)-jasmonoyl]-(S)-tyrosine (2) from the methanolic extract of flowers of broad bean (Vicia faba). Their structures were proposed on the basis of spectroscopic data (LC-MS/MS) and chromatographic properties on reversed and chiral phases and confirmed by partial syntheses. Furthermore, tyrosine conjugates of two cucurbic acid isomers (7, 8) were detected and characterized by LC-MS. Crude enzyme preparations from flowers of V. faba hydroxylated both (±)-2 and N-[(3R,7R/3S,7S)-(−)-jasmonoyl]tyramine [(±)-4] to (±)-3 and (±)-5, respectively, suggesting a possible biosynthetic relationship. In addition, a commercial tyrosinase (mushroom) and a tyrosinase-containing extract from hairy roots of red beet exhibited the same catalytic properties, but with different substrate specificities. The conjugates (±)-2, (±)-3, (±)-4, and (±)-5 exhibited in a bioassay low activity to elicit alkaloid formation in comparison to free (±)-jasmonic acid [(±)-1].
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1956
TI  - Production of (10E,12Z)-conjugated linoleic acid in yeast and tobacco seeds
JO  - BBA-Mol. Cell Biol. Lipids
PY  - 2005
SP  - 105-114
AU  - Hornung, E.
AU  - Krueger, C.
AU  - Pernstich, C.
AU  - Gipmans, M.
AU  - Porzel, A.
AU  - Feussner, I.
AU  - 
VL  - 1738
UR  - 
DO  - 10.1016/j.bbalip.2005.11.004
AB  - The polyenoic fatty acid isomerase from Propioniumbacterium acnes (PAI) was expressed in E. coli and biochemically characterized. PAI catalyzes the isomerization of a methylene-interrupted double bond system to a conjugated double bond system, creating (10E,12Z)-conjugated linoleic acid (CLA). PAI accepted a wide range of free polyunsaturated fatty acids as substrates ranging from 18:2 fatty acids to 22:6, converting them to fatty acids with two or three conjugated double bonds. For expression of PAI in yeast the PAI-sequence encoding 20 N-terminal amino acid residues was altered for optimal codon usage, yielding codon optimized PAI (coPAI). The percentage of 10,12-CLA of total esterified fatty acids was 8 times higher in yeast transformed with coPAI than in cells transformed with PAI. CLA was detected in amounts up to 5.7% of total free fatty acids in yeast transformed with coPAI but none was detected in yeast transformed with PAI. PAI or coPAI under the control of the constitutive CaMV 35S promoter or the seed-specific USP promoter was transformed into tobacco plants. CLA was only detected in seeds in coPAI-transgenic plants. The amount of CLA detected in esterified fatty acids was up to 0.3%, in free fatty acids up to 15%.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1953
TI  - Epothilone D affects cell cycle and microtubular pattern in plant cells
JO  - J. Exp. Bot.
PY  - 2005
SP  - 2131-2137
AU  - Hause, G.
AU  - Lischewski, S.
AU  - Wessjohann, L. A.
AU  - Hause, B.
AU  - 
VL  - 56
UR  - 
DO  - 10.1093/jxb/eri211
AB  - Epothilones, macrocyclic lactones from culture filtrates of the myxobacterium Sorangium cellulosum, are known as taxol-like microtubular drugs in human medicine. To date, nothing is known about the effect of epothilones on microtubules (MTs) in plant cells and/or on the plant cell cycle. As shown in this report, the treatment of tomato cell suspension cultures with epothilone D produced a continuous increase in the mitotic index. Dose–response curves revealed that epothilone D alters the mitotic index at concentrations as low as 1.5 μM. Mitotic arrest was already visible after only 2 h of treatment, and 55% of the cells were arrested after 24 h. As shown by immunocytological methods, abnormal spindles are formed during metaphase, which leads to a random distribution of chromosomes in the whole cell and prevents the formation of a metaphase plate. The process of chromosome decondensation does not seem to be affected, because micronuclei form at the same place with the distributed chromosomes. This suggests that epothilone D influences the stability of plant MTs mainly during metaphase of the mitotic cycle. In metaphase, the effects of epothilone D seem to be irreversible, because cells with an abnormal spindle could not be recovered after removal of the drug.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1949
TI  - Comparative Qualitative and Quantitative Determination of Alkaloids in Narcotic and Condiment Papaver somniferum Cultivars
JO  - J. Nat. Prod.
PY  - 2005
SP  - 666-673
AU  - Frick, S.
AU  - Kramell, R.
AU  - Schmidt, J.
AU  - Fist, A. J.
AU  - Kutchan, T. M.
AU  - 
VL  - 68
UR  - 
DO  - 10.1021/np0496643
AB  - In the present study morphinan, tetrahydrobenzylisoquinoline, benzo[c]phenanthridine, and phthalideisoquinoline alkaloids were determined qualitatively and quantitatively by HPLC and LC-MS analysis in tissues of the Tasmanian Papaver somniferum L. elite cultivar C048-6-14-64. The data were compared with the results from the low-morphine cultivar “Marianne”. In the elite cultivar, 91.2% of the latex alkaloids consist of the three pharmaceutically most valuable alkaloids: morphine, codeine, and thebaine. In the root system, the major alkaloids are sanguinarine/10-hydroxysanguinarine and dihydrosanguinarine/10-hydroxydihydrosanguinarine. In the stems and leaves of C048-6-14-64, the same alkaloids were measured as in the latex. In the stems, a gradient in relative total alkaloid content from the top downward toward the roots was observed. The concentration of morphine was decreasing toward the roots, whereas an increasing gradient from the upper to the lower stem parts was detected for codeine. The relative total alkaloid concentration in leaves remained constant; no gradient was observed. The cultivar “Marianne” displayed a shifted pattern of alkaloid accumulation and reduced levels of total alkaloid. In the condiment cultivar, 80.5% of the alkaloids of the latex consisted of the two phthalideisoquinoline alkaloids narcotoline and noscapine. Only 18.8% of the relative total alkaloid content were morphinan alkaloids. In contrast to the narcotic cultivar, in which the benzo[c]phenanthridines in roots dominated over the morphinan and tetrahydrobenzylisoquinoline alkaloids, the concentration of benzo[c]phenanthridines in “Marianne” was similar to that of morphinan and tetrahydrobenzylisoquinoline alkaloids. These data suggest a differential alkaloid regulation in each cultivar of P. somniferum.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2003
TI  - A Stilbene Synthase Gene (SbSTS1) Is Involved in Host and Nonhost Defense Responses in Sorghum
JO  - Plant Physiol.
PY  - 2005
SP  - 393-401
AU  - Yu, C. K. Y.
AU  - Springob, K.
AU  - Schmidt, J.
AU  - Nicholson, R. L.
AU  - Chu, I. K.
AU  - Yip, W. K.
AU  - Lo, C.
AU  - 
VL  - 138
UR  - 
DO  - 10.1104/pp.105.059337
AB  - A chalcone synthase (CHS)-like gene, SbCHS8, with high expressed sequence tag abundance in a pathogen-induced cDNA library, was identified previously in sorghum (Sorghum bicolor). Genomic Southern analysis revealed that SbCHS8 represents a single-copy gene. SbCHS8 expression was induced in sorghum mesocotyls following inoculation with Cochliobolus heterotrophus and Colletotrichum sublineolum, corresponding to nonhost and host defense responses, respectively. However, the induction was delayed by approximately 24 h when compared to the expression of at least one of the other SbCHS genes. In addition, SbCHS8 expression was not induced by light and did not occur in a tissue-specific manner. SbCHS8, together with SbCHS2, was overexpressed in transgenic Arabidopsis (Arabidopsis thaliana) tt4 (transparent testa) mutants defective in CHS activities. SbCHS2 rescued the ability of these mutants to accumulate flavonoids in seed coats and seedlings. In contrast, SbCHS8 failed to complement the mutation, suggesting that the encoded enzyme does not function as a CHS. To elucidate their biochemical functions, recombinant proteins were assayed with different phenylpropanoid-Coenzyme A esters. Flavanones and stilbenes were detected in the reaction products of SbCHS2 and SbCHS8, respectively. Taken together, our data demonstrated that SbCHS2 encodes a typical CHS that synthesizes naringenin chalcone, which is necessary for the formation of different flavonoid metabolites. On the other hand, SbCHS8, now retermed SbSTS1, encodes an enzyme with stilbene synthase activity, suggesting that sorghum accumulates stilbene-derived defense metabolites in addition to the well-characterized 3-deoxyanthocyanidin phytoalexins.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2002
TI  - Synthesis of multivalent aminoglycoside mimics via the Ugi multicomponent reaction
JO  - Chem. Commun.
PY  - 2005
SP  - 2116-2118
AU  - Westermann, B.
AU  - Dörner, S.
AU  - 
VL  - 2005
UR  - 
DO  - 10.1039/B501028D
AB  - The synthesis of multivalent neoglycoconjugates with 2,6-diamino-2,6-dideoxyglucose is accomplished by a flexible Ugi multicomponent approach leading to mono-, di- and tri-valent carbohydrate clusters.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2001
TI  - Dihydroxyacetone in Amino Acid Catalyzed Mannich-Type Reactions
JO  - Angew. Chem. Int. Ed.
PY  - 2005
SP  - 4077-4079
AU  - Westermann, B.
AU  - Neuhaus, C.
AU  - 
VL  - 44
UR  - 
DO  - 10.1002/anie.200500297
AB  - The C3 equivalent dihydroxyacetone was used in its protected form in proline‐catalyzed Mannich reactions (see scheme). As little as 5 mol % catalyst is required when using 2,2,2‐trifluoroethanol as solvent. The reaction is improved further (reaction time 10 min) under microwave conditions. PMP=p‐methoxyphenyl.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2000
TI  - Dihydroxyaceton in Aminosäure-katalysierten Mannich-Reaktionen
JO  - Angew. Chem.
PY  - 2005
SP  - 4145-4147
AU  - Westermann, B.
AU  - Neuhaus, C.
AU  - 
VL  - 117
UR  - 
DO  - 10.1002/ange.200500297
AB  - Das C3‐Äquivalent Dihydroxyaceton wurde in seiner geschützten Form in Prolin‐katalysierten Mannich‐Reaktionen eingesetzt (siehe Schema). Durch Verwendung von 2,2,2‐Trifluorethanol als Lösungsmittel gelang es, die Katalysatormengen auf 5 Mol‐% zu senken. Eine weitere Verbesserung bringt der Mikrowelleneinsatz, der die Reaktionszeiten auf 10 min verkürzt. PMP=p‐Methoxyphenyl.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1999
TI  - What can a chemist learn from nature’s macrocycles? – A brief, conceptual view
JO  - Mol. Divers.
PY  - 2005
SP  - 171-186
AU  - Wessjohann, L. A.
AU  - Ruijter, E.
AU  - Garcia-Rivera, D.
AU  - Brandt, W.
AU  - 
VL  - 9
UR  - 
DO  - 10.1007/s11030-005-1314-x
AB  - Macrocyclic natural products often display remarkable biological activities, and many of these compounds (or their derivatives) are used as drugs. The chemical diversity of these compounds is immense and may provide inspiration for innovative drug design. Therefore, a database of naturally occurring macrocycles was analyzed for ring size, molecular weight distribution, and the frequency of some common substructural motifs. The underlying principles of the chemical diversity are reviewed in terms of biosynthetic origin and nature’s strategies for diversity and complexity generation in relation to the structural diversity and similarities found in the macrocycle database. Finally, it is suggested that synthetic chemists should use not only nature’s molecules, but also nature’s strategies as a source of inspiration. To illustrate this, the biosynthesis of macrocycles by non-ribosomal peptide synthetases and terpene and polyketide cyclases, as well as recent advances of these strategies in an integrated synthesis/biotechnology approach are briefly reviewed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1998
TI  - Macrocycles rapidly produced by multiple multicomponent reactions including bifunctional building blocks (MiBs)
JO  - Mol. Divers.
PY  - 2005
SP  - 159-169
AU  - Wessjohann, L. A.
AU  - Ruijter, E.
AU  - 
VL  - 9
UR  - 
DO  - 10.1007/s11030-005-1313-y
AB  - Naturally occurring macrocycles often exhibit remarkable biological activities and, therefore, constitute an attractive starting point for diversity-oriented synthesis for lead discovery in drug development. Multicomponent reactions have been used for the introduction of chemical diversity in strategies towards macrocycle libraries, mostly by combinational synthesis of a linear precursor combined with a subsequent macrocyclization reaction. The Ugi reaction in particular may be used for the macrocyclization itself as well, and a library of natural product-like macrocycles can be constructed in a single step from simple precursors. The efficiency and versatility of both strategies is immense and is exemplarily illustrated by the construction of small libraries of cyclopeptide alkaloid derivatives and biaryl ether macrocycles. The syntheses of the latter compound group are examples of multiple multicomponent macrocyclizations including bifunctional building blocks (M3iB3 or MiB), of which the Ugi-MiBs and their variations are discussed in more detail.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1997
TI  - Diversity Oriented One-Pot Synthesis of Complex Macrocycles: Very Large Steroid-Peptoid Hybrids from Multiple Multicomponent Reactions Including Bifunctional Building Blocks
JO  - Angew. Chem. Int. Ed.
PY  - 2005
SP  - 4785-4790
AU  - Wessjohann, L. A.
AU  - Voigt, B.
AU  - Rivera, D. G.
AU  - 
VL  - 44
UR  - 
DO  - 10.1002/anie.200500019
AB  - Up to 16 new bonds connect 12 building blocks to form 54‐membered macrocycles (46‐membered example shown) in a one‐pot procedure combining bifunctional components with multicomponent reactions. The large rings are not made of repetitive subunits and form an ideal basis for the fast construction of libraries of chiral host molecules.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1996
TI  - Diversity Oriented One-Pot Synthesis of Complex Macrocycles: Very Large Steroid-Peptoid Hybrids from Multiple Multicomponent Reactions Including Bifunctional Building Blocks
JO  - Angew. Chem.
PY  - 2005
SP  - 4863-4868
AU  - Wessjohann, L. A.
AU  - Voigt, B.
AU  - Rivera, D. G.
AU  - 
VL  - 117
UR  - 
DO  - 10.1002/ange.200500019
AB  - Bis zu 54‐gliedrige Makrocylen (z. B. der 46‐gliedrige, im Bild gezeigte Ring) entstehen im Eintopfverfahren aus 12 Bausteinen unter Knüpfung von bis zu 16 neuen Bindungen durch die geschickte Kombination difunktioneller Bausteine mit Multikomponentenreaktionen. Die Riesenringe ohne repetitive Elemente sind damit eine ideale Grundlage für die schnelle Synthese von Bibliotheken chiraler Wirtmoleküle.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1995
TI  - Aporphine and proaporphine alkaloids from Stephania rotunda
JO  - Vietnam J. Chem.
PY  - 2005
SP  - 619-623
AU  - Trinh, T. T.
AU  - Tran, V. S.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - 
VL  - 43
UR  - http://vjs.ac.vn/index.php/vjchem/issue/view/373
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1994
TI  - Isoquinolone and protoberberine alkaloids from Stephania rotunda
JO  - Pharmazie
PY  - 2005
SP  - 701-704
AU  - Thuy, T. T.
AU  - Porzel, A.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - Sung, T. V.
AU  - 
VL  - 60
UR  - 
AB  - Chemical investigation of Stephania rotunda Lour. growing in Viet Nam led to the isolation and structural elucidation of three new alkaloids, 5-hydroxy-6,7-dimethoxy-3,4-dihydroisoquinolin-1(2H)-one (1), thaicanine 4-O-β-L-glucoside (6), as well as (–)-thaicanine N-oxide (4-hydroxycorynoxidine) (8), along with 23 known alkaloids. These structures were determined on the basis of MS and NMR spectroscopic data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1993
TI  - Characterisation of alkaloids from Stephania rotunda
JO  - Adv. Nat. Sci. (Vietnam)
PY  - 2005
SP  - 299-312
AU  - Thuy, T. T.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - Sung, T. V.
AU  - 
VL  - 6
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1991
TI  - Unusual Bioactive 4-Oxo-2-alkenoic Fatty Acids from Hygrophorus eburneus
JO  - Z. Naturforsch. B
PY  - 2005
SP  - 25-32
AU  - Teichert, A.
AU  - Lübken, T.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 60
UR  - 
DO  - 10.1515/znb-2005-0105
AB  - From fruit bodies of the basidiomycete Hygrophorus eburneus (Bull.: Fr.) Fr. (Tricholomataceae) eight fatty acids (C16, C18) with γ -oxocrotonate partial structure could be isolated. Initial tests demonstrate their bactericidal and fungicidal activity. The structures of (2E,9E)-4-oxooctadeca- 2,9,17-trienoic acid (1), (2E,11Z)-4-oxooctadeca-2,11,17-trienoic acid (2), (E)-4-oxohexadeca-2,15- dienoic acid (3), (E)-4-oxooctadeca-2,17-dienoic acid (4), (2E,9E)-4-oxooctadeca-2,9-dienoic acid (5), (2E,11Z)-4-oxooctadeca-2,11-dienoic acid (6), (E)-4-oxohexadec-2-enoic acid (7), and (E)-4- oxooctadec-2-enoic acid (8) were elucidated on the basis of their spectroscopic data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1990
TI  - Bioaktive Sekundärmetaboliten aus der Gattung Hygrophorus (Basidiomycetes)
JO  - Z. Mykol.
PY  - 2005
SP  - 53-61
AU  - Teichert, A.
AU  - Lübken, T.
AU  - Kummer, M.
AU  - Besl, H.
AU  - Haslberger, H.
AU  - Arnold, N.
AU  - 
VL  - 71
UR  - https://www.dgfm-ev.de/publikationen/bioaktive-sekundaermetaboliten-aus-der-gattung-hygrophorus-basidiomycetes
AB  - Die fungizide Wirkung von verschiedenen Rohextrakten von 23 Arten der Gattung Hygrophorus gegen Cladosporium cucumerinum wird gezeigt. Als Wirkprinzip konnten ungewöhnliche Fettsäuren und die Hygrophorone A-G identifiziert werden.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1986
TI  - Analysis of Benzylisoquinoline-Type Alkaloids by Electrospray Tandem Mass Spectrometry and Atmospheric Pressure Photoionization
JO  - Eur. J. Mass Spectrom.
PY  - 2005
SP  - 325-333
AU  - Schmidt, J.
AU  - Raith, K.
AU  - Boettcher, C.
AU  - Zenk, M. H.
AU  - 
VL  - 11
UR  - 
DO  - 10.1255/ejms.745
AB  - Benzylisoquinoline alkaloids found in the Papaveraceae family play a major role in pharmaceutical biology. This is the first systematic study dealing with electrospray tandem mass spectrometry (ESI-MS/MS) of all benzylisoquinolines found as biogenetic precursors of morphinan alkaloids. Tandem mass spectral data are presented for norlaudanosoline, laudanosoline, 4′-O-methyl-norlaudanosoline, 6-O-methyl-norlaudanosoline, norcoclaurine, coclaurine, N-methylcoclaurine, N-methyl-3′-hydroxycoclaurine, N-methyl-3′-O-methylcoclaurine, norreticuline and reticuline. This study compares results obtained using an ion trap mass spectrometer with those obtained using a triple quadrupole one. The results highlight the differences between the tandem-in-time versus the tandem-in-space principle, often hampering the development of ESI-MS/MS libraries. In addition, the use of the atmospheric pressure photoionisation technique for the analysis of such substances is discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1985
TI  - Highly Substituted Tetrahydropyrones from Hetero-Diels−Alder Reactions of 2-Alkenals with Stereochemical Induction from Chiral Dienes
JO  - J. Org. Chem.
PY  - 2005
SP  - 2820-2823
AU  - Ruijter, E.
AU  - Schültingkemper, H.
AU  - Wessjohann, L. A.
AU  - 
VL  - 70
UR  - 
DO  - 10.1021/jo0488311
AB  - A new method for the stereoselective synthesis of libraries of 2,3,5-trisubstituted tetrahydro-γ-pyrones and the corresponding tetrahydropyran-4-ols is reported. Dienes with a chiral moiety at position 5 were synthesized starting from (triphenylphosphoranylidene)acetone. In hetero-Diels−Alder (HDA) reactions, especially with α,β-unsaturated aldehydes, they induce diastereomeric ratios from 4:1 to 14:1. Through selective epimerization and reduction, further building blocks are available. These constitute ideal starting points for their use in the total synthesis of complex polyketide macrocycles, especially with the vinyl group available for metathetic coupling.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1979
TI  - Chemoenzymatic Dynamic Kinetic Resolution of Acyloins
JO  - J. Org. Chem.
PY  - 2005
SP  - 9551-9555
AU  - Ödman, P.
AU  - Wessjohann, L. A.
AU  - Bornscheuer, U. T.
AU  - 
VL  - 70
UR  - 
DO  - 10.1021/jo051661n
AB  - Acyloins (α-hydroxy ketones) are important building blocks in organic synthesis, e.g., for the total synthesis of epothilones. Optically pure acyloins can be obtained by lipase-catalyzed kinetic resolution (KR) of the racemate with, for example, Burkholderia cepacia lipase, but this process suffers from a yield limitation of 50%. To devise a dynamic kinetic resolution (DKR), we studied the racemization of two different acyloins and corresponding esters with various amine bases and ion exchangers. No combination of base and solvent was found that could selectively racemize the acyloin or corresponding ester under the conditions needed for a DKR. In contrast to bases, acidic resins (ARs) were found to racemize the acyloins selectively in n-hexane and in water. Unfortunately, the AR deactivated the lipase, preventing a one-pot DKR. Minor side reactions involving the AR, the substrate acyloin, and the vinyl ester acyl donor were also observed. However, an efficient DKR was made possible by the spatial separation of lipase and ion exchanger, with enzymatic transesterification and AR-catalyzed racemization taking place simultaneously in two compartments connected by a pump loop. The conversion of substrate alcohol was 91%, the selectivity toward the product butyrate ester 90%, and the enantiomeric excess of the (S)-product 93% ee.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1938
TI  - The Functional Role of Selenocysteine (Sec) in the Catalysis Mechanism of Large Thioredoxin Reductases: Proposition of a Swapping Catalytic Triad Including a Sec-His-Glu State
JO  - ChemBioChem
PY  - 2005
SP  - 386-394
AU  - Brandt, W.
AU  - Wessjohann, L. A.
AU  - 
VL  - 6
UR  - 
DO  - 10.1002/cbic.200400276
AB  - Thioredoxin reductases catalyse the reduction of thioredoxin disulfide and some other oxidised cell constituents. They are homodimeric proteins containing one FAD and accepting one NADPH per subunit as essential cofactors. Some of these reductases contain a selenocysteine at the C terminus. Based on the X‐ray structure of rat thioredoxin reductase, homology models of human thioredoxin reductase were created and subsequently docked to thioredoxin to model the active complex. The formation of a new type of a catalytic triad between selenocysteine, histidine and a glutamate could be detected in the protein structure. By means of DFT (B3LYP, lacv3p**) calculations, we could show that the formation of such a triad is essential to support the proton transfer from selenol to a histidine to stabilise a selenolate anion, which is able to interact with the disulfide of thioredoxin and catalyses the reductive disulfide opening. Whereas a simple proton transfer from selenocysteine to histidine is thermodynamically disfavoured by some 18 kcal mol −1 , it becomes favoured when the carboxylic acid group of a glutamate stabilises the formed imidazole cation. An identical process with a cysteine instead of selenocysteine will require 4 kcal mol −1  more energy, which corresponds to a calculated equilibrium shift of ∼1000:1 or a 10 3  rate acceleration: a value close to the experimental one of about 10 2  times. These results give new insights into the catalytic mechanism of thioredoxin reductase and, for the first time, explain the advantage of the incorporation of a selenocysteine instead of a cysteine residue in a protein.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1937
TI  - Microwave-accelerated asymmetric allylations using cysteine derived oxazolidine and thiazolidine palladium complexes
JO  - J. Mol. Catal. A
PY  - 2005
SP  - 235-238
AU  - Braga, A. L.
AU  - Silveira, C. C.
AU  - de Bolster, M. W. G.
AU  - Schrekker, H. S.
AU  - Wessjohann, L. A.
AU  - Schneider, P. H.
AU  - 
VL  - 239
UR  - 
DO  - 10.1016/j.molcata.2005.06.008
AB  - A set of enantiopure oxazolidine–thioether and thiazolidine–alcohol palladium complexes catalyze the microwave-mediated enantioselective allylation of rac-1,3-diphenyl-2-propenyl acetate with dimethyl malonate. Good yields and ee&#39;s were achieved in reaction times of 2 min instead of hours with conventional heating.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1936
TI  - Catalytic enantioselective aryl transfer: asymmetric addition of boronic acids to aldehydes using pyrrolidinylmethanols as ligands
JO  - Tetrahedron Lett.
PY  - 2005
SP  - 7827-7830
AU  - Braga, A. L.
AU  - Lüdtke, D. S.
AU  - Schneider, P. H.
AU  - Vargas, F.
AU  - Schneider, A.
AU  - Wessjohann, L. A.
AU  - Paixão, M. W.
AU  - 
VL  - 46
UR  - 
DO  - 10.1016/j.tetlet.2005.09.026
AB  - Pyrrolidinylmethanols, easily accessible from readily available (S)-proline, were applied in zinc-catalyzed addition of arylboronic acids to aromatic aldehydes; the reaction was found to proceed in excellent yields and high enantioselectivities (up to 98% ee).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1935
TI  - A New Cysteine-Derived Ligand as Catalyst for the Addition of Diethylzinc to Aldehydes: The Importance of a ‘Free’ Sulfide Site for Enantioselectivity
JO  - Synthesis
PY  - 2005
SP  - 588-594
AU  - Braga, A. L.
AU  - Alves, E. F.
AU  - Silveira, C. C.
AU  - Zeni, G.
AU  - Appelt, H. R.
AU  - Wessjohann, L. A.
AU  - 
VL  - 2005
UR  - 
DO  - 10.1055/s-2005-861801
AB  - New chiral sulfides and disulfides were synthesized from readily available and inexpensive cysteine by straightforward methods in order to elucidate the relative importance of the various donor atoms (N, O, S) available in free or alkylated form resulting in covalent or dative bonds to the metal, respectively. Their application in the addition of diethylzinc to aldehydes provides secondary alcohols with up to 99% ee, and S-configuration, when catalytic amounts of disulfide ligands with the ability to form an S-Zn bond were used. In contrast to this, benzyl alcohols with the opposite absolute configuration R could be achieved, albeit with decreased yield and enantioselectivity, by the use of alkylated sulfide ligands.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1934
TI  - A chiral disulfide derived from (R)-cysteine in the enantioselective addition of diethylzinc to aldehydes: loading effect and asymmetric amplification
JO  - J. Mol. Catal. A
PY  - 2005
SP  - 47-50
AU  - Braga, A. L.
AU  - Lüdtke, D. S.
AU  - Wessjohann, L. A.
AU  - Paixão, M. W.
AU  - Schneider, P. H.
AU  - 
VL  - 229
UR  - 
DO  - 10.1016/j.molcata.2004.11.004
AB  - A chiral disulfide derived from (R)-cysteine is described to catalyze the enantioselective addition of diethylzinc to benzaldehyde with high enantioselectivities at different catalyst loadings. Nonlinear effects have also been evaluated and the relationship between the ee of the catalyst and the ee of the product has been found to be strictly linear.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1933
TI  - Formation of a complex pattern of sinapate esters in Brassica napus seeds, catalyzed by enzymes of a serine carboxypeptidase-like acyltransferase family?
JO  - Phytochemistry
PY  - 2005
SP  - 1334-1345
AU  - Baumert, A.
AU  - Milkowski, C.
AU  - Schmidt, J.
AU  - Nimtz, M.
AU  - Wray, V.
AU  - Strack, D.
AU  - 
VL  - 66
UR  - 
DO  - 10.1016/j.phytochem.2005.02.031
AB  - Members of the Brassicaceae accumulate complex patterns of sinapate esters, as shown in this communication with seeds of oilseed rape (Brassica napus). Fifteen seed constituents were isolated and identified by a combination of high-field NMR spectroscopy and high resolution electrospray ionisation mass spectrometry. These include glucose, gentiobiose and kaempferol glycoside esters as well as sinapine (sinapoylcholine), sinapoylmalate and an unusual cyclic spermidine amide. One of the glucose esters (1,6-di-O-sinapoylglucose), two gentiobiose esters (1-O-caffeoylgentiobiose and 1,2,6′-tri-O-sinapoylgentiobiose) and two kaempferol conjugates [4′-(6-O-sinapoylglucoside)-3,7-di-O-glucoside and 3-O-sophoroside-7-O-(2-O-sinapoylglucoside)] seem to be new plant products. Serine carboxypeptidase-like (SCPL) acyltransferases catalyze the formation of sinapine and sinapoylmalate accepting 1-O-β-acetal esters (1-O-β-glucose esters) as acyl donors. To address the question whether the formation of other components of the complex pattern of the sinapate esters in B. napus seeds is catalyzed via 1-O-sinapoyl-β-glucose, we performed a seed-specific dsRNAi-based suppression of the sinapate glucosyltransferase gene (BnSGT1) expression. In seeds of BnSGT1-suppressing plants the amount of sinapoylglucose decreased below the HPLC detection limit resulting in turn in the disappearance or marked decrease of all the other sinapate esters, indicating that formation of the complex pattern of these esters in B. napus seeds is dependent on sinapoylglucose. This gives rise to the assumption that enzymes of an SCPL acyltransferase family catalyze the appropriate transfer reactions to synthesize the accumulating esters.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 1932
TI  - Penicillin G Amidase-Catalysed Hydrolysis of Phenylacetic Hydrazides on a Solid Phase: A New Route to Enzyme-Cleavable Linkers
JO  - Adv. Synth. Catal.
PY  - 2005
SP  - 963-966
AU  - Basso, A.
AU  - Ebert, C.
AU  - Gardossi, L.
AU  - Linda, P.
AU  - Tran Phuong, T.
AU  - Zhu, M.
AU  - Wessjohann, L.
AU  - 
VL  - 347
UR  - 
DO  - 10.1002/adsc.200505038
AB  - A novel catalytic property of penicillin G amidase (PGA) is described. Unexpectedly, the enzyme can hydrolyse hydrazide bonds with good efficiency, and in solution the enzyme shows a selectivity that is similar to phenylacetamides. The hydrolysis of phenylacetic hydrazides releases hydrazine, but no inhibition due to the formation of such reactive compounds was observed. This novel catalytic property was assayed also on a solid phase as a pioneering route for the design of enzyme‐cleavable linkers and masked scavengers for ketones. On a solid phase a phenylacetic hydrazide compound was chemically synthesised on PEGA1900 and PEGA+ (two co‐polymers of acrylamide and ethylene glycol) and the efficiency of PGA in the release of phenylacetic acid depended on the diffusion of the protein inside the polymer. On PEGA+ the enzyme, as previously described, shows a good diffusion due to an improved electrostatic interaction with PGA thus achieving good hydrolytic conversions.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1931
TI  - Gedanken zum Mechanismus der Serinproteasen, Teil II–Dipeptidyl-Peptidase IV (DP IV/CD 26)
JO  - Acta Fac. Pharm. Univ. Comen.
PY  - 2005
SP  - 7-21
AU  - Barth, A.
AU  - Thondorf, I.
AU  - Gebauer, S.
AU  - Brandt, W.
AU  - Neubert, K.
AU  - Stano, J.
AU  - Psenak, M.
AU  - Kovacs, P.
AU  - 
VL  - 52
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1928
TI  - Catalytic Addition of Homoenolates to Imines - The Homo-Mannich Reaction
JO  - Synlett
PY  - 2005
SP  - 473-476
AU  - Abbas, M.
AU  - Neuhaus, C.
AU  - Krebs, B.
AU  - Westermann, B.
AU  - 
VL  - 2005
UR  - 
DO  - 10.1055/s-2005-862378
AB  - For the first time, homo-Mannich reactions with unmasked homoenolates have been achieved by adding homoenolate precursor 1 and imines 5. The key to this reaction is the right choice of the Lewis acids - Cu(OTf)2 proved to be most suitable for preparing the homoenolate and activation of the imine. An asymmetric catalytic version of this reaction is provided by using chiral, non-­racemic phenyl-derived bisoxazolidine as ligand for the Lewis acid.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 1942
TI  - A short route for the synthesis of “sweet” macrocycles via a click-dimerization–ring-closing metathesis approach
JO  - Chem. Commun.
PY  - 2005
SP  - 2852-2854
AU  - Dörner, S.
AU  - Westermann, B.
AU  - 
VL  - 2005
UR  - 
DO  - 10.1039/B502682B
AB  - A facile and flexible approach for the preparation of macrocyclic molecules containing different carbohydrate moieties is presented, employing the reaction cascade: click-dimerization and ring-closing metathesis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 133
TI  - Strategies for Total and Diversity-Oriented Synthesis of Natural Product(-Like) Macrocycles
T2  - Natural Product Synthesis I
PB  - Top. Curr. Chem.
PY  - 2005
SP  - 137-184
AU  - Wessjohann, L. A.
AU  - Ruijter, E.
AU  - 
VL  - 243
UR  - 
SN  - 978-3-540-31476-9
DO  - 10.1007/b96883
AB  - Numerous biologically active macrocycles, including antibiotic, antifungal, and antitumor compounds, have been isolated from natural sources. In recent years the number of such structures has steadily increased, predominantly by polyketide- and peptide-derived compounds from various microorganisms. Macrocycles can combine the right amount of rigidity and flexibility and often exhibit unrivalled activity, thereby deviating from the current paradigm that medicinally active compounds should be small, nitrogen-rich heterocycles. Their challenging structures and intriguing activities have motivated organic chemists to find synthetic access to these compounds. Total synthesis plays a crucial role in the medicinal chemistry efforts towards macrocycles of already defined activity, as well as in the development of new and selective macrocyclization reactions. For lead discovery purposes, however, isolation or classical total synthesis may lack structural variability or prove to be too time consuming and impractical. A more rapid solution may be provided by diversity-oriented synthesis (DOS) of natural product-like molecules. A compromise between total synthesis and combinatorial chemistry, DOS concerns molecules displaying sufficient molecular complexity to resemble natural products, but features a more straightforward synthesis, thus allowing introduction of significant structural diversity. A brief review of flexible macrocyclization strategies and applications of DOS is given, as well as an overview of contributions to total and diversity-oriented synthesis of macrocycles from our laboratory.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2069
TI  - New Scavenger Resin for the Reversible Linking and Monoprotection of Functionalized Aromatic Aldehydes
JO  - Org. Lett.
PY  - 2004
SP  - 3921-3924
AU  - Zhu, M.
AU  - Ruijter, E.
AU  - Wessjohann, L. A.
AU  - 
VL  - 6
UR  - 
DO  - 10.1021/ol048610h
AB  - Polymer-supported benzylhydrazines were synthesized using poly(ethylene glycol) acrylamide (PEGA) resin. They can be used to scavenge electrophiles reactive with hydrazine. Especially aromatic aldehydes can be captured selectively, monoprotected, and reversibly linked in the presence of other functional groups, including electrophilic ones. Various reactions can be performed on these protectively linked aldehydes, which afterward can be released either with full restoration of the aldehyde function or, alternatively, with simultaneous conversion.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2068
TI  - Synthesis, inhibitory and activation properties of prenyldiphosphate mimics for aromatic prenylations with ubiA-prenyl transferase
JO  - ARKIVOC
PY  - 2004
SP  - 79
AU  - Zakharova, S.
AU  - Fulhorst, M.
AU  - Luczak, L.
AU  - Wessjohann, L.
AU  - 
VL  - 2004
UR  - 
DO  - 10.3998/ark.5550190.0005.d10
AB  - 4-Hydroxybenzoate oligoprenyl transferase from E. coli (ubiA-prenyl transferase) is a crucial enzyme for ubiquinone biosynthesis. It catalyzes the formation of 3-oligoprenyl-4-hydroxybenzoates like geranyl hydroxybenzoate (GHB, 23) from geranyl pyrophosphate (GPP, 22). Several analogues and mimics of geranyl pyrophosphate have been prepared for an examination of their ability to inhibit the enzyme. 7,11-Dimethyl-3-oxododeca-6,10-dienoic acid (2), 3-hydroxy7,11- dimethyldodeca-6,10-dienoic acid (3), 2-hydroxy-4,8-dimethyl-3,7-nonadienylphosphonic acid (4), and tripotassium [[(4E)-5,9-dimethyldeca-4,8-dienyl]phosphinato](difluoro)methylphosphonate (5) were synthesized from geraniol. .-2,.-1-Dihydroxylated farnesyl diphosphate 6 was prepared from trans,trans-farnesol. All compounds were tested for enzyme inhibition in a competitive assay with natural substrate. The effect of these compounds on ubiA-prenyltransferase activity varied substantially, ranging from almost full inhibition to, surprisingly, enhanced enzymatic activity at low concentrations by some compounds. A special, EDTAmodifyable magnesium effect is discussed as potential reason.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2067
TI  - Diastereoselective synthesis of homologous bicyclic lactams––potential building blocks for peptide mimics
JO  - Tetrahedron Lett.
PY  - 2004
SP  - 5983-5986
AU  - Westermann, B.
AU  - Diedrichs, N.
AU  - Krelaus, R.
AU  - Walter, A.
AU  - Gedrath, I.
AU  - 
VL  - 45
UR  - 
DO  - 10.1016/j.tetlet.2004.06.051
AB  - Bicyclic lactams serve as building blocks for the synthesis of conformationally restricted peptides. A route to these building blocks is described. They can serve as cis- and trans-peptide bond surrogates. Due to the de novo synthesis, both enantiomeric forms of these products can be produced. Key steps are a lipase-catalyzed saponification of oximes and a highly diastereoselective cyclization utilizing phenylselenyl bromide. In addition, attachment to a solid support has been achieved.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2066
TI  - Chromium-mediated aldol and homoaldol reactions on solid support directed towards an iterative polyol strategy
JO  - Tetrahedron Lett.
PY  - 2004
SP  - 9073-9078
AU  - Wessjohann, L. A.
AU  - Wild, H.
AU  - Schrekker, H. S.
AU  - 
VL  - 45
UR  - 
DO  - 10.1016/j.tetlet.2004.10.038
AB  - Chromium-Reformatsky and chromium-homoaldol reactions run under neutral and mild reaction conditions. They are highly chemoselective, tolerant towards most common functional groups, and are not prone to retroaldol reactions. Initial studies directed to transfer these homogeneous chromium-mediated solution-phase reactions to solid phase are presented. The main objective was to develop a methodology to aid a combinatorial iterative strategy to polyols (polyketides) on solid phase. A general reactivity problem was observed with polystyrene based resins compared to the solution-phase reactions, independent if the electrophilic (aldehyde) or nucleophilic (bromide) end of the polyol chain was supported to the resin. A complicated penetration, or loss of the polar solvent environment after penetration into the resin, might be responsible for the reduced reactivity. Application of either a soluble polystyrene resin or a polystyrene resin with a polar polyethylene glycol tether resulted in improved yields.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2013
TI  - Constituents of Jatropha unicostata
JO  - Biochem. Syst. Ecol.
PY  - 2004
SP  - 219-220
AU  - Franke, K.
AU  - Nasher, A. K.
AU  - Schmidt, J.
AU  - 
VL  - 32
UR  - 
DO  - 10.1016/S0305-1978(03)00140-6
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2009
TI  - Modeling the E. coli 4-hydroxybenzoic acid oligoprenyltransferase (ubiA transferase) and characterization of potential active sites
JO  - J. Mol. Model.
PY  - 2004
SP  - 317-327
AU  - Bräuer, L.
AU  - Brandt, W.
AU  - Wessjohann, L. A.
AU  - 
VL  - 10
UR  - 
DO  - 10.1007/s00894-004-0197-6
AB  - 4-Hydroxybenzoate oligoprenyltransferase of E. coli, encoded in the gene ubiA, is an important key enzyme in the biosynthetic pathway to ubiquinone. It catalyzes the prenylation of 4-hydroxybenzoic acid in position 3 using an oligoprenyl diphosphate as a second substrate. Up to now, no X-ray structure of this oligoprenyltransferase or any structurally related enzyme is known. Knowledge of the tertiary structure and possible active sites is, however, essential for understanding the catalysis mechanism and the substrate specificity.With homology modeling techniques, secondary structure prediction tools, molecular dynamics simulations, and energy optimizations, a model with two putative active sites could be created and refined. One active site selected to be the most likely one for the docking of oligoprenyl diphosphate and 4-hydroxybenzoic acid is located near the N-terminus of the enzyme. It is widely accepted that residues forming an active site are usually evolutionary conserved within a family of enzymes. Multiple alignments of a multitude of related proteins clearly showed 100% conservation of the amino acid residues that form the first putative active site and therefore strongly support this hypothesis. However, an additional highly conserved region in the amino acid sequence of the ubiA enzyme could be detected, which also can be considered a putative (or rudimentary) active site. This site is characterized by a high sequence similarity to the aforementioned site and may give some hints regarding the evolutionary origin of the ubiA enzyme.Semiempirical quantum mechanical PM3 calculations have been performed to investigate the thermodynamics and kinetics of the catalysis mechanism. These results suggest a near SN1 mechanism for the cleavage of the diphosphate ion from the isoprenyl unit. The 4-hydroxybenzoic acid interestingly appears not to be activated as benzoate anion but rather as phenolate anion to allow attack of the isoprenyl cation to the phenolate, which appeared to be the rate limiting step of the whole process according to our quantum chemical calculations. Our models are a basis for developing inhibitors of this enzyme, which is crucial for bacterial aerobic metabolism.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2008
TI  - A Proposed Mechanism for the Reductive Ring Opening of the Cyclodiphosphate MEcPP, a Crucial Transformation in the New DXP/MEP Pathway to Isoprenoids Based on Modeling Studies and Feeding Experiments
JO  - ChemBioChem
PY  - 2004
SP  - 311-323
AU  - Brandt, W.
AU  - Dessoy, M. A.
AU  - Fulhorst, M.
AU  - Gao, W.
AU  - Zenk, M. H.
AU  - Wessjohann, L. A.
AU  - 
VL  - 5
UR  - 
DO  - 10.1002/cbic.200300743
AB  - Experimental and theoretical investigations concerning the second‐to‐last step of the DXP/MEP pathway in isoprenoid biosynthesis in plants are reported. The proposed intrinsic or late intermediates 4‐oxo‐DMAPP ( 12  ) and 4‐hydroxy‐DMAPP ( 11  ) were synthesized in deuterium‐ or tritium‐labeled form according to new protocols especially adapted to work without protection of the diphosphate moiety. When the labeled compounds MEcPP ( 7  ), 11  , and 12   were applied to chromoplast cultures, aldehyde 12   was not incorporated. This finding is in agreement with a mechanistic and structural model of the responsible enzyme family: a three‐dimensional model of the fragment L271–A375 of the enzyme GcpE of  Streptomyces coelicolor including NADPH, the Fe 4 S 4  cluster, and MEcPP ( 7  ) as ligand has been developed based on homology modeling techniques. The model has been accepted by the Protein Data Bank (entry code 1OX2). Supported by this model, semiempirical PM3 calculations were performed to analyze the likely catalysis mechanism of the reductive ring opening of MEcPP ( 7  ), hydroxyl abstraction, and formation of HMBPP ( 8  ). The mechanism is characterized by a proton transfer (presumably from a conserved arginine 286) to the substrate, accompanied by a ring opening without high energy barriers, followed by the transfer of two electrons delivered from the Fe 4 S 4  cluster, and finally proton transfer from a carboxylic acid side chain to the hydroxyl group to be removed from the ligand as water. The proposed mechanism is in agreement with all known experimental findings and the arrangement of the ligand within the enzyme. Thus, a very likely mechanism for the second to last step of the DXP/MEP pathway in isoprenoid biosynthesis in plants is presented. A principally similar mechanism is also expected for the reductive dehydroxylation of HMBPP ( 8  ) to IPP ( 9  ) and DMAPP ( 10  ) in the last step.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2007
TI  - Further constituents from Ophiopogon japonicus
JO  - Vietnam J. Chem.
PY  - 2004
SP  - 261-264
AU  - Anh, N. T. H.
AU  - Sung, T. V.
AU  - Wessjohann, L. A.
AU  - 
VL  - 42
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2036
TI  - Enantioselective reduction of prochiral ketones by chromium(II) amino acid complexes
JO  - Tetrahedron: Asymmetry
PY  - 2004
SP  - 1735-1744
AU  - Micskei, K.
AU  - Hajdu, C.
AU  - Wessjohann, L. A.
AU  - Mercs, L.
AU  - Kiss-Szikszai, A.
AU  - Patonay, T.
AU  - 
VL  - 15
UR  - 
DO  - 10.1016/j.tetasy.2004.04.017
AB  - The reduction of prochiral ketones has been performed by Cr(II) L-amino acid complexes in aqueous DMF solution under mild conditions in good yields and moderate (up to 58%) ee values. The dependence of the yield and enantioselectivity on various factors such as the structure of the ligand, pH and the solvent has also been investigated. A mechanism based on SET from the Cr(II) ion followed by protonation by water and the formation of an organochromium intermediate is also proposed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2031
TI  - Hygrophorones A–G: fungicidal cyclopentenones from Hygrophorus species (Basidiomycetes)
JO  - Phytochemistry
PY  - 2004
SP  - 1061-1071
AU  - Lübken, T.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Arnold, N.
AU  - Wessjohann, L.
AU  - 
VL  - 65
UR  - 
DO  - 10.1016/j.phytochem.2004.01.023
AB  - Twenty new 5-(hydroxyalkyl)-2-cyclopentenone derivatives (hygrophorones) could be isolated from Hygrophorus latitabundus, H. olivaceoalbus, H. persoonii, and H. pustulatus. Their fungicidal activity was exemplarily tested. The hygrophorones have structural similarities to the antibiotic pentenomycin. Chemically, hygrophorones are 2-cyclopentenones with hydroxy or acetoxy substituents at C-4 and/or C-5. An odd-numbered 1′ oxidized alkyl chain (C11, C13, C15, or C17) is attached at C-5. In addition, from H. persoonii the new γ-butyrolactone derivative [5-(E)-2-hydroxytetradexylidene-5H-furan-2-one] could be isolated. Some hygrophorones are responsible for the color reaction of the stipes of these fungi upon treatment with potassium hydroxide solution. Structural elucidations are based on 1D (1H, 13C) and 2D (COSY, NOESY, HSQC, HMBC) NMR spectroscopic analyses as well as HR-FT-ICR-MS investigations.A series of new cyclopentenone derivatives and butyrolactones with antifungical activity could be isolated from fruit bodies of the basidiomyceteous genus Hygrophorus. Structural elucidations are based on 1D and 2D NMR spectroscopic analyses as well as HR-FT-ICR-MS investigations.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2029
TI  - Preparation of peptide-like bicyclic lactams via a sequential Ugi reaction––olefin metathesis approach
JO  - Tetrahedron Lett.
PY  - 2004
SP  - 5987-5990
AU  - Krelaus, R.
AU  - Westermann, B.
AU  - 
VL  - 45
UR  - 
DO  - 10.1016/j.tetlet.2004.06.052
AB  - Bicyclic lactams, suitable for incorporation into conformationally restricted peptide mimics, can be synthesized by using olefinic starting materials for the Ugi multicomponent reaction, setting up an olefin metathesis reaction, that is easily carried out with the Grubbs catalyst. The influence of the different starting materials is evaluated. In addition, the utilization of chiral, nonracemic amines is described.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2026
TI  - Chemie von Cladonia furcata und Cladonia rangiformis
JO  - Herzogia
PY  - 2004
SP  - 51-58
AU  - Huneck, S.
AU  - Feige, G. B.
AU  - Schmidt, J.
AU  - 
VL  - 17
UR  - https://herzogia.blam-bl.de/herzogia/herzogia-downloads/herzogia-downloads-17-2004.html
AB  - Eleven collections of Cladonia furcata and fourteen of Cladonia rangiformis, mainly from Saxony Anhalt (Germany) have been analyzed for their lichen substances by HPLC and HPLC-MS. The main compounds of C. furcata are fumarprotocetraric acid, atranorin, protocetraric acid, rangiformic acid, bourgeanic acid, norrangiformic acid and the new lichen metabolite 1-methyl 3,4-dicarboxydecanoate. C. rangiformis is characterized by atranorin, rangiformic acid, norrangiformic acid and 1-methyl 3,4-dicarboxyhexadecanoate, while bourgeanic acid is absent.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2025
TI  - 1,2-Dehydroreticuline synthase, the branch point enzyme opening the morphinan biosynthetic pathway
JO  - Phytochemistry
PY  - 2004
SP  - 1039-1046
AU  - Hirata, K.
AU  - Poeaknapo, C.
AU  - Schmidt, J.
AU  - Zenk, M. H.
AU  - 
VL  - 65
UR  - 
DO  - 10.1016/j.phytochem.2004.02.015
AB  - A synthase which oxidizes (S)-reticuline to 1,2-dehydroreticuline has been found to occur in seedlings of opium poppy (Papaver somniferum L.). Due to its instability, this enzyme could only be partly purified (ca. 5-fold enrichment). Partial characterization at this stage of purification showed that it does not need a redox cofactor and accepts both (S)-reticuline and (S)-norreticuline as substrates. [1-2H, 13C]-(R,S)-reticuline was enzymatically converted into [1-13C]-dehydroreticuline, which has been identified by mass spectrometry. Release of the hydrogen atom in position C-1 of the isoquinoline alkaloid during the oxidative conversion, was exploited as a sensitive assay system for this enzyme. The enzyme has a pH optimum of 8.75, a temperature optimum of 37 °C and the apparent KM value for the substrate reticuline was shown to be 117 μM. Moreover it could be demonstrated by sucrose density gradient centrifugation that the enzyme is located in vesicles of varying size. In combination with the previously discovered strictly stereoselective and NADPH dependent 1,2-dehydroreticuline reductase the detection of this enzyme, the 1,2-dehydroreticuline synthase, provides the necessary inversion of configuration and completes the pathway from two molecules of L-tyrosine via (S)-norcoclaurine to (R)-reticuline in opium poppy involving a total number of 11 enzymes.A synthase which oxidizes (S)-reticuline to 1,2-dehydroreticuline has been found to occur in seedlings of opium poppy (Papaver somniferum L.)
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2023
TI  - Site-directed mutagenesis and protein 3D-homology modelling suggest a catalytic mechanism for UDP-glucose-dependent betanidin 5-O-glucosyltransferase from Dorotheanthus bellidiformis
JO  - Plant J.
PY  - 2004
SP  - 319-333
AU  - Hans, J.
AU  - Brandt, W.
AU  - Vogt, T.
AU  - 
VL  - 39
UR  - 
DO  - 10.1111/j.1365-313X.2004.02133.x
AB  - In livingstone daisy (Dorotheanthus bellidiformis ), betanidin 5‐O‐glucosyltransferase (UGT73A5) is involved in the regiospecific glucosylation of betanidin and various flavonols. Based on sequence alignments several amino acid candidates which might be essential for catalysis were identified. The selected amino acids of the functionally expressed protein, suggested to be involved in substrate binding and turnover, were substituted via site‐directed mutagenesis. The substitution of two highly conserved amino acids, Glu378, located in the proposed UDP‐glucose binding site, and His22, located close to the N‐terminus, led to the complete loss of enzyme activity. A 3D model of this regiospecific betanidin and flavonoid glucosyltransferase was constructed and the active site modelled. This model was based on the crystallographic structure of a bacterial UDP‐glucose‐dependent glucosyltransferase from Amycolatopsis orientalis  used as a template and the generated null  mutations. To explain the observed inversion in the configuration of the bound sugar, semiempirical calculations favour an SN‐1 reaction, as one plausible alternative to the generally proposed SN‐2 mechanism discussed for plant natural product glucosyltransferases. The calculated structural data do not only explain the abstraction of a proton from the acceptor betanidin, but further imply that the reaction mechanism might also involve a catalytic triad, with similarities described for the serine protease family.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2016
TI  - In Vitro and In Vivo Production of New Aminocoumarins by a Combined Biochemical, Genetic, and Synthetic Approach
JO  - Chem. Biol.
PY  - 2004
SP  - 173-183
AU  - Galm, U.
AU  - Dessoy, M. A.
AU  - Schmidt, J.
AU  - Wessjohann, L. A.
AU  - Heide, L.
AU  - 
VL  - 11
UR  - 
DO  - 10.1016/j.chembiol.2004.01.012
AB  - The aminocoumarin antibiotics clorobiocin, novobiocin, and coumermycin A1 are inhibitors of bacterial gyrase. Their chemical structures contain amide bonds, formed between an aminocoumarin ring and an aromatic acyl component, which is 3-dimethylallyl-4-hydroxybenzoate in the case of novobiocin and clorobiocin. These amide bonds are formed under catalysis of the gene products of cloL, novL, and couL, respectively. We first examined the substrate specificity of the purified amide synthetases CloL, NovL, and CouL for the various analogs of the prenylated benzoate moiety. We then generated new aminocoumarin antibiotics by feeding synthetic analogs of the 3-dimethylallyl-4-hydroxybenzoate moiety to a mutant strain defective in the biosynthesis of the prenylated benzoate moiety. This resulted in the formation of 32 new aminocoumarin compounds. The structures of these compounds were elucidated using FAB-MS and 1H-NMR spectroscopy.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2014
TI  - Transformation of opium poppy (Papaver somniferum L.) with antisense berberine bridge enzyme gene (anti-bbe) via somatic embryogenesis results in an altered ratio of alkaloids in latex but not in roots
JO  - Transgenic Res.
PY  - 2004
SP  - 607-613
AU  - Frick, S.
AU  - Chitty, J. A.
AU  - Kramell, R.
AU  - Schmidt, J.
AU  - Allen, R. S.
AU  - Larkin, P. J.
AU  - Kutchan, T. M.
AU  - 
VL  - 13
UR  - 
DO  - 10.1007/s11248-004-2892-6
AB  - The berberine bridge enzyme cDNA bbe from Papaver somniferumL. was transformed in antisense orientation into seedling explants of the industrial elite line C048-6-14-64. In this way, 84 phenotypically normal T0 plants derived from embryogenic callus cultures were produced. The selfed progeny of these 84 plants yielded several T1 plants with an altered alkaloid profile. One of these plants T1-47, and its siblings T2-1.2 and T2-1.5 are the subject of the present work. The transformation of these plants was evaluated by PCR, and northern and Southern hybridisation. The transgenic plants contained one additional copy of the transgene. The alkaloid content in latex and roots was determined with HPLC and LC-MS. We observed an increased concentration of several pathway intermediates from all biosynthetic branches, e.g., reticuline, laudanine, laudanosine, dehydroreticuline, salutaridine and (S)-scoulerine. The transformation altered the ratio of morphinan and tetrahydrobenzylisoquinoline alkaloids in latex but not the benzophenanthridine alkaloids in roots. The altered alkaloid profile is heritable at least to the T2 generation. These results are the first example of metabolic engineering of the alkaloid pathways in opium poppy and, to our knowledge, the first time that an alkaloid biosynthetic gene has been transformed into the native species, followed by regeneration into a mature plant to enable analyses of the effect of the transgene on metabolism over several generations.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2062
TI  - Profiling of Arabidopsis Secondary Metabolites by Capillary Liquid Chromatography Coupled to Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry
JO  - Plant Physiol.
PY  - 2004
SP  - 548-559
AU  - von Roepenack-Lahaye, E.
AU  - Degenkolb, T.
AU  - Zerjeski, M.
AU  - Franz, M.
AU  - Roth, U.
AU  - Wessjohann, L.
AU  - Schmidt, J.
AU  - Scheel, D.
AU  - Clemens, S.
AU  - 
VL  - 134
UR  - 
DO  - 10.1104/pp.103.032714
AB  - Large-scale metabolic profiling is expected to develop into an integral part of functional genomics and systems biology. The metabolome of a cell or an organism is chemically highly complex. Therefore, comprehensive biochemical phenotyping requires a multitude of analytical techniques. Here, we describe a profiling approach that combines separation by capillary liquid chromatography with the high resolution, high sensitivity, and high mass accuracy of quadrupole time-of-flight mass spectrometry. About 2,000 different mass signals can be detected in extracts of Arabidopsis roots and leaves. Many of these originate from Arabidopsis secondary metabolites. Detection based on retention times and exact masses is robust and reproducible. The dynamic range is sufficient for the quantification of metabolites. Assessment of the reproducibility of the analysis showed that biological variability exceeds technical variability. Tools were optimized or established for the automatic data deconvolution and data processing. Subtle differences between samples can be detected as tested with the chalcone synthase deficient tt4 mutant. The accuracy of time-of-flight mass analysis allows to calculate elemental compositions and to tentatively identify metabolites. In-source fragmentation and tandem mass spectrometry can be used to gain structural information. This approach has the potential to significantly contribute to establishing the metabolome of Arabidopsis and other model systems. The principles of separation and mass analysis of this technique, together with its sensitivity and resolving power, greatly expand the range of metabolic profiling.
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions
ER  - 


TY  - JOUR
ID  - 2060
TI  - Stilbene, ferulic acid and its derivatives from the roots of Angelica sinensis
JO  - Vietnam J. Chem.
PY  - 2004
SP  - 508-512
AU  - Van, N. T. H.
AU  - Anh, N. T. H.
AU  - Sung, T. V.
AU  - Franke, K.
AU  - Wessjohann, L.
AU  - 
VL  - 42
UR  - http://vjs.ac.vn/index.php/vjchem/issue/view/368
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2054
TI  - A New Type of Floral Oil from Malpighia coccigera (Malpighiaceae) and Chemical Considerations on the Evolution of Oil Flowers
JO  - Chem. Biodivers.
PY  - 2004
SP  - 1519-1528
AU  - Seipold, L.
AU  - Gerlach, G.
AU  - Wessjohann, L.
AU  - 
VL  - 1
UR  - 
DO  - 10.1002/cbdv.200490112
AB  - New, partially acetylated dihydroxy fatty acids could be identified in the floral oil of Malpighia coccigera  (Malpighiaceae): 7‐OAc,3‐OH 20 : 0, 7‐OAc,3‐OH 22 : 0, 9‐OAc,3‐OH 22 : 0, 9‐OAc,5‐OH 22 : 0, 3,9‐diOAc 22 : 0, 9‐OAc,3‐OH 24 : 0 , and 11‐OAc,5‐OH 24 : 0 . The substitution patterns of all hitherto undescribed dihydroxylated and additionally identified monohydroxylated fatty acids are in agreement with a polyketide analogous biosynthesis. Intermediates may be 3‐acetoxy fatty acids (C16, C18, and C20), known from flower secretions of other phylogenetically unrelated plant families. A possible relationship between plant epicuticular wax and floral oil biosynthesis is discussed. It may explain why an independent but convergent development of oil flowers and flower oils in unrelated plant families was possible.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2050
TI  - Involvement of an Oxidation-Reduction Equilibrium in Chromium-Mediated Enantioselective Nozaki–Hiyama Reactions
JO  - Adv. Synth. Catal.
PY  - 2004
SP  - 731-736
AU  - Schrekker, H.
AU  - Micskei, K.
AU  - Hajdu, C.
AU  - Patonay, T.
AU  - de Bolster, M.
AU  - Wessjohann, L.
AU  - 
VL  - 346
UR  - 
DO  - 10.1002/adsc.200404021
AB  - Ligand induced enantioselective versions of the chromium(II)‐mediated Nozaki–Hiyama reaction to homoallyl alcohols proved to be very difficult to achieve, especially if any other nucleophile than the parent allylchromium(III) species was applied. Also, the reaction is frequently accompanied by the formation of oxidation side products, predominantly allyl ketones. This can be explained by an Oppenauer–(Meerwein–PonndorfVerley) type mechanism (OMPV reaction). The addition of an enantiopure ligand to racemic chromium homoallyl alcoholate intermediates produced enantiomerically enriched homoallyl alcohols with an enantiomeric excess of up to 32%. This observation not only supports that the proposed OMPV oxidation‐reduction equilibrium plays a crucial role in Nozaki–Hiyama reactions, but also proves its involvement in enantioselective versions.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2049
TI  - First Generation Cysteine- and Methionine-Derived Oxazolidine and Thiazolidine Ligands for Palladium-Catalyzed Asymmetric Allylations
JO  - Eur. J. Org. Chem.
PY  - 2004
SP  - 2715-2722
AU  - Schneider, P.
AU  - Schrekker, H.
AU  - Silveira, C.
AU  - Wessjohann, L.
AU  - Braga, A.
AU  - 
VL  - 2004
UR  - 
DO  - 10.1002/ejoc.200300675
AB  - A new series of enantiopure oxazolidine‐thioether and thiazolidine‐alcohol ligands have been synthesized from L ‐cysteine, S‐methyl‐L ‐cysteine, and L ‐methionine in a straightforward manner that allows numerous structural variations to be formed. These types of ligands have not previously been used in asymmetric palladium‐catalyzed allylations and their efficacy was explored in the reaction of rac‐1,3‐diphenyl‐2‐propenyl acetate with dimethyl malonate. The reaction proceeds in excellent yield and with good enantioselectivity. The palladium catalyst derived from N‐benzyl‐2,2‐dimethyl‐4‐(2‐thiapropyl)oxazolidine (12 ) provides the allylation product in a quantitative yield and with an enantiomeric excess of 94%.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2048
TI  - Synthesis and resolution of a key building block for epothilones: a comparison of asymmetric synthesis, chemical and enzymatic resolution
JO  - Tetrahedron: Asymmetry
PY  - 2004
SP  - 2861-2869
AU  - Scheid, G.
AU  - Ruijter, E.
AU  - Konarzycka-Bessler, M.
AU  - Bornscheuer, U. T.
AU  - Wessjohann, L. A.
AU  - 
VL  - 15
UR  - 
DO  - 10.1016/j.tetasy.2004.06.048
AB  - The asymmetric synthesis and kinetic resolution of a series of acyloins (α-hydroxy ketones) suitable as building blocks for the northern half of epothilones was studied. Three methods were applied to obtain nonracemic compounds at the eventual epothilone C15-position: asymmetric synthesis with Evans’ auxiliary, chemical resolution and enzymatic resolution. The success rate in small scale applications increased in the order given, and the enzymatic resolution was studied in more detail. Out of a set of nine lipases and esterases, lipases from Burkholderia cepacia, Pseudomonas sp., lipase B from Candida antarctica and recombinant esterases from Streptomyces diastatochromogenes exhibited the highest enantioselectivities with E-values ranging from 60 to &gt;200. Pig liver esterase exhibited inverse enantiopreference and only with recombinant enzyme could a moderate selectivity (E = 50, commercial PLE: E = 8) be observed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2047
TI  - A New Route to Protected Acyloins and Their Enzymatic Resolution with Lipases
JO  - Eur. J. Org. Chem.
PY  - 2004
SP  - 1063-1074
AU  - Scheid, G.
AU  - Kuit, W.
AU  - Ruijter, E.
AU  - Orru, R.
AU  - Henke, E.
AU  - Bornscheuer, U.
AU  - Wessjohann, L.
AU  - 
VL  - 2004
UR  - 
DO  - 10.1002/ejoc.200300338
AB  - A series of 16 different 3‐acyloxy methyl ketones, the acyloin acetates and butyrates (±)‐5 , was synthesised by a straightforward new method through alkylation of tert‐butyl 2‐acyloxyacetoacetates 3 , followed by chemoselective dealkoxycarbonylation of the tert‐butyloxycarbonyl group in the presence of other ester groups. Subsequent hydrolysis of (±)‐5  can be achieved with base to give racemic acyloins 6 , or with lipase catalysis to afford the corresponding non‐racemic acyloins (S )‐6 . The remaining (R )‐acyloin esters 5  can be racemised and resubjected to the procedure, or hydrolysed chemically. The kinetic resolution with two of the six tested enzymes, CAL‐B and BCL (PS) lipase, proceeded selectively [enantiomeric ratio (E ) values between 50 and &gt; 200] and most of the acyloins (S )‐6  were obtained in very high enantiomeric excesses (up to &gt; 99% ee ).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2045
TI  - Evaluation of the mass spectrometric fragmentation of codeine and morphine after 13C-isotope biosynthetic labeling
JO  - Phytochemistry
PY  - 2004
SP  - 1413-1420
AU  - Poeaknapo, C.
AU  - Fisinger, U.
AU  - Zenk, M. H.
AU  - Schmidt, J.
AU  - 
VL  - 65
UR  - 
DO  - 10.1016/j.phytochem.2004.05.005
AB  - All major fragment ions of codeine and morphine were elucidated using LC–electrospray MS/MS and high resolution FT-ICR-MS combined with an IRMPD system. Nanogram quantities of labeled codeine were isolated and purified from Papaver somniferum seedlings, which were grown for up to 9 days in the presence of [ring-13C6]-l-tyrosine, [ring-13C6]-tyramine and [1,2-13C2], [6-O-methyl 13C]-(R,S)-coclaurine. The labeling degree of codeine up to 57% into morphinans was observed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2044
TI  - Endogenous formation of morphine in human cells
JO  - Proc. Natl. Acad. Sci. U.S.A.
PY  - 2004
SP  - 14091-14096
AU  - Poeaknapo, C.
AU  - Schmidt, J.
AU  - Brandsch, M.
AU  - Dräger, B.
AU  - Zenk, M. H.
AU  - 
VL  - 101
UR  - 
DO  - 10.1073/pnas.0405430101
AB  - Morphine is a plant (opium poppy)-derived alkaloid and one of the strongest known analgesic compounds. Studies from several laboratories have suggested that animal and human tissue or fluids contain trace amounts of morphine. Its origin in mammals has been believed to be of dietary origin. Here, we address the question of whether morphine is of endogenous origin or derived from exogenous sources. Benzylisoquinoline alkaloids present in human neuroblastoma cells (SH-SY5Y) and human pancreas carcinoma cells (DAN-G) were identified by GC/tandem MS (MS/MS) as norlaudanosoline (DAN-G), reticuline (DAN-G and SH-SY5Y), and morphine (10 nM, SH-SY5Y). The stereochemistry of reticuline was determined to be 1-(S). Growth of the SH-SY5Y cell line in the presence of 18O2 led to the [18O]-labeled morphine that had the molecular weight 4 mass units higher than if grown in 16O2, indicating the presence of two atoms of 18O per molecule of morphine. Growth of DAN-G cells in an 18O2 atmosphere yielded norlaudanosoline and (S)-reticuline, both labeled at only two of the four oxygen atoms. This result clearly demonstrates that all three alkaloids are of biosynthetic origin and suggests that norlaudanosoline and (S)-reticuline are endogenous precursors of morphine. Feeding of [ring-13C6]-tyramine, [1-13C, N- 13CH3]-(S)-reticuline and [N-CD3]-thebaine to the neuroblastoma cells led each to the position-specific labeling of morphine, as established by GC/MS/MS. Without doubt, human cells can produce the alkaloid morphine. The studies presented here serve as a platform for the exploration of the function of “endogenous morphine” in the neurosciences and immunosciences.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2043
TI  - Functional Analysis of the Final Steps of the 1-Deoxy-d-xylulose 5-phosphate (DXP) Pathway to Isoprenoids in Plants Using Virus-Induced Gene Silencing
JO  - Plant Physiol.
PY  - 2004
SP  - 1401-1413
AU  - Page, J. E.
AU  - Hause, G.
AU  - Raschke, M.
AU  - Gao, W.
AU  - Schmidt, J.
AU  - Zenk, M. H.
AU  - Kutchan, T. M.
AU  - 
VL  - 134
UR  - 
DO  - 10.1104/pp.103.038133
AB  - Isoprenoid biosynthesis in plant plastids occurs via the 1-deoxy-d-xylulose 5-phosphate (DXP) pathway. We used tobacco rattle virus (TRV) to posttranscriptionally silence the expression of the last two enzymes of this pathway, the IspG-encoded (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase (HDS) and the IspH-encoded isopentenyl/dimethylallyl diphosphate synthase (IDDS), as well as isopentenyl/dimethylallyl diphosphate isomerase (IDI), the enzyme that interconverts IPP and DMAPP. TRV-IspG and TRV-IspH infected Nicotiana benthamiana plants had albino leaves that contained less than 4% of the chlorophyll and carotenoid pigments of control leaves. We applied [13C]DXP and [14C]DXP to silenced leaves and found that 2-C-methyl-d-erythritol 2,4-cyclodiphosphate accumulated in plants blocked at HDS while DXP, (E)-4-hydroxy-3-methylbut-2-enyl phosphate and (E)-2-methylbut-2-ene-1,4-diol accumulated in IDDS-blocked plants. Albino leaves from IspG- and IspH-silenced plants displayed a disorganized palisade mesophyll, reduced cuticle, fewer plastids, and disrupted thylakoid membranes. These findings demonstrate the participation of HDS and IDDS in the DXP pathway in plants, and support the view that plastid isoprenoid biosynthesis is metabolically and physically segregated from the mevalonate pathway. IDI-silenced plants had mottled white-pale green leaves with disrupted tissue and plastid structure, and showed an 80% reduction in pigments compared to controls. IPP pyrophosphatase activity was higher in chloroplasts isolated from IDI-silenced plants than in control plant chloroplasts. We suggest that a low level of isoprenoid biosynthesis via the DXP pathway can occur without IDI but that this enzyme is required for full function of the DXP pathway.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2041
TI  - A new cardenolide from the roots of Streptocaulon tomentosum
JO  - Fitoterapia
PY  - 2004
SP  - 779-781
AU  - Myint Khine, M.
AU  - Franke, K.
AU  - Arnold, N.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Wessjohann, L. A.
AU  - 
VL  - 75
UR  - 
DO  - 10.1016/j.fitote.2004.06.007
AB  - A new cardenolide, (17α)-H-periplogenin-3-O-β-d-glucopyranosyl-(1–4)-2-O-acetyl-3-O-methyl-β-fucopyranoside (1), was isolated from the roots of Streptocaulon tomentosum.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 140
TI  - New Results on the Conformations of Potent DP IV (CD26) Inhibitors bearing the N-terminal MWP Structural Motif
T2  - Dipeptidyl Aminopeptidases in Health and Disease
PB  - Adv. Exp. Med. Biol.
PY  - 2004
SP  - 65-68
AU  - Mrestani-Klaus, C.
AU  - Brandt, W.
AU  - Faust, J.
AU  - Wrenger, S.
AU  - Reinhold, D.
AU  - Ansorge, S.
AU  - Neubert, K.
AU  - 
VL  - 524
UR  - 
DO  - 10.1007/0-306-47920-6_7
AB  - Conformational analysis by NMR spectroscopy and molecular modeling revealed a left-handed PPII helix-like structure for Trp2-Tat(1–9) (cis and trans) and an even more flexible structure for TXA2-R(1–9).PPII helices form a well-defined structural class comparable with the other structures defined in proteins and are characterized by exposed, mobile structures with 4–8 residues, mostly found on the protein surface. Polyproline II helices are mainly identified by their torsion angles of φ∼−75° and Ψ∼145−. They do not form regular interchain hydrogen bonds, but are hydrogen bonded with water molecules. PPII helices have a strong preference for the amino acid proline, although it is not necessarily present. These features were also reported for the parent peptide Tat(1–9)4 as well as for the well known DP IV substrates neuropeptide Y and pancreatic polypeptide5 suggesting that PPII-like helical structures represent a favored structural class for the interaction with DP IV.Thus, the considerable enhancement of the inhibition capacity of both Trp2-Tat(1–9) and TXA2-R(1–9) compared to the moderate inhibitor Tat(1–9)2, Ki=2.68±0.01 10−4 M, can only be due to tryptophan in the second position suggesting that its side chain is favored to exhibit attractive hydrophobic interactions with DP IV compared with aspartic acid.On the other hand, we could show recently that Tat(1–9) and its analogues as well as TXA2-R(1–9) inhibit DP IV according to different inhibition mechanisms (Lorey et al., manuscript submitted). One possible explanation for these findings might be enzyme-ligand interactions relying on multiple weak binding sites as described for PPII helices5 rather than specific lock and key binding. Certainly, only an X-ray structure of DP IV would help to understand the interaction of DP IV with inhibitors.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 139
TI  - Alanyl-Aminopeptidases in Human T Cells
T2  - Aminopeptidases in Biology and Disease
PB  - Proteases in Biology and Disease
PY  - 2004
SP  - 201-227
AU  - Lendeckel, U.
AU  - Bukowska, A.
AU  - Lättig, J. H.
AU  - Brandt, W.
AU  - 
VL  - 2
UR  - 
DO  - 10.1007/978-1-4419-8869-0_10
AB  - Inhibition of the enzymatic activity of alanyl-aminopeptidase leads to strong immunosuppression both in vitro and in vivo. Mechanisms involved include growth arrest, induction of immunosuppressive cytokines (TGF-ß1), reduced expression of inflammatory or T cell stimulating cytokines (IL-2, IL-12), and modulation of T cell signalling pathways. Thus, T cells appear to represent a major cellular target for the pharmacological treatment of T cell mediated diseases by virtue of aminopeptidase inhibitor administration. Membrane (APN) and cytosol alanyl-aminopeptidase (ApPS), both implicated in a variety of cellular functions, show similar substrate specifity and inhibitor sensitivity. Furthermore, both enzymes are expressed in practically all T cell subsets, including the population of natural regulatory T cells that was shown recently to control the immunological tolerance to self-antigens. While the involvement of APN and ApPS in the pathological immune response is evident, the precise molecular mechanisms remain to be identified. The development of inhibitors specific for APN and ApPS is an attractive field of study and would allow determination of the individual contribution of either enzyme in the immune response.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 138
TI  - The Specificity of DP IV for Natural Substrates is Peptide Structure Determined
T2  - Dipeptidyl Aminopeptidases in Health and Disease
PB  - Adv. Exp. Med. Biol.
PY  - 2004
SP  - 57-63
AU  - Kühn-Wache, K.
AU  - Hoffmann, T.
AU  - Manhart, S.
AU  - Brandt, W.
AU  - Demuth, H.-U.
AU  - 
VL  - 524
UR  - 
DO  - 10.1007/0-306-47920-6_6
AB  - Our results indicate that the substrate properties of peptides are encoded by their own structure. That means, that substrate characteristics depend not only on the primary structure around the catalytic site rather C-terminal located secondary interactions strongly influence the binding and catalysis of the substrates. Such interaction sites seem to force the ligand in a proper orientation to the active site of DP IV. As result of these relations the hydrolysis of peptides with non-proline and non-alanine residues in P1-position (Ser, Val, Gly) becomes possible in longer peptides.Such specific secondary interactions opens the opportunity for development of new inhibitors.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 137
TI  - Die Verteilung von Flechteninhaltsstoffen in Lecanora muralis und Lecidea inops und die Abhängigkeit der Usninsäure-Konzentration vom Substrat und von den Jahreszeiten bei Lecanora muralis
T2  - Contributions to Lichenology: Festschrift in Honour of Hannes Hertel
PB  - Bibliotheca Lichenologica
PY  - 2004
SP  - 211-222
AU  - Huneck, S.
AU  - Lumbsch, H. T.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - 
VL  - 88
UR  - https://www.schweizerbart.de/publications/detail/isbn/9783443580674/Bibliotheca_Lichenologica_Band_88_Dobbel
AB  - 
A2  - Döbbeler, P. &amp; Rambold, G., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 136
TI  - SEEDS OF GRAPES OF VITIS VINIFERA VAR ALPHONSE LAVALLEE (ROYAL): A POSSIBLE MODEL TISSUE FOR STUDYING TOCOTRIENOL BIOSYNTHESIS
T2  - I International Symposium on Grapevine Growing, Commerce and Research
PB  - ISHS Acta Hortic.
PY  - 2004
SP  - 415-424
AU  - Horvath, G. Y.
AU  - Guisez, Y.
AU  - Biebaut, E.
AU  - Caubergs, R. J.
AU  - Horemans, N.
AU  - Wessjohann, L.
AU  - 
VL  - 652
UR  - 
DO  - 10.17660/ActaHortic.2004.652.55
AB  - Tocopherols and tocotrienols are phytochemicals generally known as vitamin E. Structurally they are very similar sharing an identical aromatic moiety (chromanol head) and an isoprenoid side chain that only differs in the degree of saturation. Tocopherols are widely distributed throughout the plant kingdom, found in practically all plant tissues and located in the inner envelope membrane of plastids. In contrast to these well characterized tocopherols little is known on the presence, location and synthesis of tocotrienols. Studies so far have been hampered by the lack of a suitable model tissue in which high tocotrienol synthesis rates could be demonstrated. Here it is shown irrevocably that tocotrienols are present in seeds of mature grapes at a relatively high concentration of (33,2 +/- 6,0) μg tocotrienols / g dry weight. Showing a distribution pattern between the - and - isomers of respectively 40 and 60 %. These data are in strong contrast with the general idea that tocotrienols are only present in monocotyledonous plants. In leaves or flowers of the grape plants on the other hand, no measurable tocotrienol concentrations were detected. Tocopherols were present in all tested tissues with highest concentrations in green leaves (30 μg tocopherols / g dry weight) and lowest in flesh of grapes (5 μg tocotrienols / g dry weight). Oil extracted from the grapes was 25-fold enriched in tocotrienols. To study the biosynthesis of tocotrienols a new procedure was developed mainly differing from original methods described in Methods of enzymology by threlfall et al. who worked on complete plants, and by Soll working on chloroplasts extracted from green tissues, none of the plant tissues Threlfall and Soll discribe produce tocotrienols. With the use of radioactive labeled precursors de novo synthesis of tocotrienols in dissected endosperm of developing grape seeds (45 DAF) was demonstrated. The use of endosperm of developing grapes as a model tissue to study tocotrienol location, biosynthesis and function is discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2105
TI  - Steroidal glycosides from Ophiopogon Japonicus
JO  - Vietnam J. Chem.
PY  - 2003
SP  - 136-142
AU  - Nguyen, T. H. A.
AU  - Sung, T. V.
AU  - Wessjohann, L.
AU  - 
VL  - 41
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2103
TI  - Detoxification of ferulic acid by ectomycorrhizal fungi
JO  - Mycorrhiza
PY  - 2003
SP  - 117-121
AU  - Münzenberger, B.
AU  - Hammer, E.
AU  - Wray, V.
AU  - Schauer, F.
AU  - Schmidt, J.
AU  - Strack, D.
AU  - 
VL  - 13
UR  - 
DO  - 10.1007/s00572-003-0226-9
AB  - The ectomycorrhizal fungi Laccaria amethystina and Lactarius deterrimus grown in liquid culture were used to study the fate of added ferulic acid. Laccaria amethystina degraded ferulic acid to the major metabolite vanillic acid. The intermediate vanillin was not detected. Lactarius deterrimus showed a completely different detoxification pattern. Two dimers and one trimer of ferulic acid could be identified as polymerization products of this fungus. A bioassay of the possible biological activities of ferulic acid and vanillic acid on these fungi revealed that vanillic acid was less toxic than ferulic acid for Laccaria amethystina but that both phenolic acids were toxic for Lactarius deterrimus. The results are discussed with respect to ectomycorrhizal fungal growth in the organic layer of forest soils and between living root cells of ectomycorrhizas.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2099
TI  - Heptazoline - A carbazol alkaloid extracted from Clausena heptaphilla (Roxb.) W &amp; ARN
JO  - Pharm. J. Vietnam
PY  - 2003
SP  - 11-12
AU  - Luu, D. H.
AU  - Porzel, A.
AU  - 
VL  - 11
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2098
TI  - Different modes of dipeptidyl peptidase IV (CD26) inhibition by oligopeptides derived from the N-terminus of HIV-1 Tat indicate at least two inhibitor binding sites
JO  - Eur. J. Biochem.
PY  - 2003
SP  - 2147-2156
AU  - Lorey, S.
AU  - Stöckel-Maschek, A.
AU  - Faust, J.
AU  - Brandt, W.
AU  - Stiebitz, B.
AU  - Gorrell, M. D.
AU  - Kähne, T.
AU  - Mrestani-Klaus, C.
AU  - Wrenger, S.
AU  - Reinhold, D.
AU  - Ansorge, S.
AU  - Neubert, K.
AU  - 
VL  - 270
UR  - 
DO  - 10.1046/j.1432-1033.2003.03568.x
AB  - Dipeptidyl peptidase IV (DP IV, CD26) plays an essential role in the activation and proliferation of lymphocytes, which is shown by the immunosuppressive effects of synthetic DP IV inhibitors. Similarly, both human immunodeficiency virus‐1 (HIV‐1) Tat protein and the N‐terminal peptide Tat(1–9) inhibit DP IV activity and T cell proliferation. Therefore, the N‐terminal amino acid sequence of HIV‐1 Tat is important for the inhibition of DP IV. Recently, we characterized the thromboxane A2 receptor peptide TXA2‐R(1–9), bearing the N‐terminal MWP sequence motif, as a potent DP IV inhibitor possibly playing a functional role during antigen presentation by inhibiting T cell‐expressed DP IV [Wrenger, S., Faust, J., Mrestani‐Klaus, C., Fengler, A., Stöckel‐Maschek, A., Lorey, S., Kähne, T., Brandt, W., Neubert, K., Ansorge, S. &amp; Reinhold, D. (2000) J. Biol. Chem. 275 , 22180–22186]. Here, we demonstrate that amino acid substitutions at different positions of Tat(1–9) can result in a change of the inhibition type. Certain Tat(1–9)‐related peptides are found to be competitive, and others linear mixed‐type or parabolic mixed‐type inhibitors indicating different inhibitor binding sites on DP IV, at the active site and out of the active site. The parabolic mixed‐type mechanism, attributed to both non‐mutually exclusive inhibitor binding sites of the enzyme, is described in detail. From the kinetic investigations and molecular modeling experiments, possible interactions of the oligopeptides with specified amino acids of DP IV are suggested. These findings give new insights for the development of more potent and specific peptide‐based DP IV inhibitors. Such inhibitors could be useful for the treatment of autoimmune and inflammatory diseases.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2096
TI  - Isolation and Identification of Trace Lignans, Arctiin and Arctigenin, in Arctium lappa L. Leaves
JO  - Chin. J. Chromatogr.
PY  - 2003
SP  - 52-55
AU  - Liu, S.
AU  - Chen, K.
AU  - Schliemann, W.
AU  - Schmidt, J.
AU  - Strack, D.
AU  - 
VL  - 21
UR  - http://open.oriprobe.com/articles/5545714/Isolation_and_Identification_of_Trace_Lignans__Arc.htm
AB  - 
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2093
TI  - A new synthesis of [26,28-2H6]brassinolide and [26,28-2H6]castasterone via an unusual methyl migration
JO  - J. Label. Compd. Rad.
PY  - 2003
SP  - 231-242
AU  - Kolbe, A.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Adam, G.
AU  - 
VL  - 46
UR  - 
DO  - 10.1002/jlcr.662
AB  - Deuterium‐labelled brassinosteroids, namely [26,28‐2H6]castasterone, 8 , and [26,28‐2H6]brassinolide, 9 , were synthesized starting from 6,6‐ ethylenedioxy‐20‐formyl‐2α,3α‐isopropylidenedioxy‐5α‐pregnane, 1 , and 3‐[2H3]methyl‐but‐1‐yne‐[4,4,4‐2H3], 11 . Upon alkylating cleavage of the epoxide 6  with trimethylaluminium‐n‐butyllithium an unusual migration of a neighbouring [2H3]methyl group takes place to afford deuteriation at positions 26 and 28.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2092
TI  - Evidence for Estrogen Receptor β-Selective Activity of Vitex agnus-castus and Isolated Flavones
JO  - Planta Med.
PY  - 2003
SP  - 945-947
AU  - Jarry, H.
AU  - Spengler, B.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Wuttke, W.
AU  - Christoffel, V.
AU  - 
VL  - 69
UR  - 
DO  - 10.1055/s-2003-45105
AB  - Recent cell culture experiments indicated that extracts of Vitex agnus-castus (VAC) may contain yet unidentified phytoestrogens. Estrogenic actions are mediated via estrogen receptors (ER). To investigate whether VAC compounds bind to the currently known isoforms ERα or ERß, ligand binding assays (LBA) were performed. Subtype specific ER-LBA revealed a binding of VAC to ERß only. To isolate the ERß-selective compounds, the extract was fractionated by bio-guidance. The flavonoid apigenin was isolated and identified as the most active ERß-selective phytoestrogen in VAC. Other isolated compounds were vitexin and penduletin. These data demonstrate that the phytoestrogens in VAC are ERß-selective.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2091
TI  - A Novel Mg2+-dependent O-Methyltransferase in the Phenylpropanoid Metabolism of Mesembryanthemum crystallinum
JO  - J. Biol. Chem.
PY  - 2003
SP  - 43961-43972
AU  - Ibdah, M.
AU  - Zhang, X.-H.
AU  - Schmidt, J.
AU  - Vogt, T.
AU  - 
VL  - 278
UR  - 
DO  - 10.1074/jbc.M304932200
AB  - Upon irradiation with elevated light intensities, the ice plant (Mesembryanthemum crystallinum) accumulates a complex pattern of methylated and glycosylated flavonol conjugates in the upper epidermal layer. Identification of a flavonol methylating activity, partial purification of the enzyme, and sequencing of the corresponding peptide fragments revealed a novel S-adenosyl-l-methionine-dependent O-methyltransferase that was specific for flavonoids and caffeoyl-CoA. Cloning and functional expression of the corresponding cDNA verified that the new methyltransferase is a multifunctional 26.6-kDa Mg2+-dependent enzyme, which shows a significant sequence similarity to the cluster of caffeoyl coenzyme A-methylating enzymes. Functional analysis of highly homologous members from chickweed (Stellaria longipes), Arabidopsis thaliana, and tobacco (Nicotiana tabacum) demonstrated that the enzymes from the ice plant, chickweed, and A. thaliana possess a broader substrate specificity toward o-hydroquinone-like structures than previously anticipated for Mg2+-dependent O-methyltransferases, and are distinctly different from the tobacco enzyme. Besides caffeoyl-CoA and flavonols, a high specificity was also observed for caffeoylglucose, a compound never before reported to be methylated by any plant O-methyltransferase. Based on phylogenetic analysis of the amino acid sequence and differences in acceptor specificities among both animal and plant O-methyltransferases, we propose that the enzymes from the Centrospermae, along with the predicted gene product from A. thaliana, form a novel subclass within the caffeoyl coenzyme A-dependent O-methyltransferases, with potential divergent functions not restricted to lignin monomer biosynthesis.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2090
TI  - Mechanism of Action of the Diazabicyclononanone-type κ-Agonists
JO  - J. Med. Chem.
PY  - 2003
SP  - 1383-1389
AU  - Holzgrabe, U.
AU  - Brandt, W.
AU  - 
VL  - 46
UR  - 
DO  - 10.1021/jm0210360
AB  - The 2,4-di-2-pyridyl-3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9-one 1,5-diester HZ2 was recently found to exhibit high affinity and selectivity to the κ-opioid receptor (KOR) in combination with an unusually long duration of action. Docking of HZ2 to the putative binding site model of the KOR revealed HZ2 to be tightly sitting in the binding pocket. Strong interactions, especially salts bridges between the protonated nitrogens of HZ2 and the glutamic acids 209 and 297, nicely explain the high affinity of HZ2 to the KOR. A formation of a hemiaminal bond between the keto carbonyl group of HZ2 and a lysine residue (Lys200) may explain the long duration of action.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2086
TI  - Biochemical and Molecular Characterization of a Hydroxyjasmonate Sulfotransferase from Arabidopsis thaliana
JO  - J. Biol. Chem.
PY  - 2003
SP  - 17895-17900
AU  - Gidda, S. K.
AU  - Miersch, O.
AU  - Levitin, A.
AU  - Schmidt, J.
AU  - Wasternack, C.
AU  - Varin, L.
AU  - 
VL  - 278
UR  - 
DO  - 10.1074/jbc.M211943200
AB  - 12-Hydroxyjasmonate, also known as tuberonic acid, was first isolated from Solanum tuberosum and was shown to have tuber-inducing properties. It is derived from the ubiquitously occurring jasmonic acid, an important signaling molecule mediating diverse developmental processes and plant defense responses. We report here that the gene AtST2a from Arabidopsis thaliana encodes a hydroxyjasmonate sulfotransferase. The recombinant AtST2a protein was found to exhibit strict specificity for 11- and 12-hydroxyjasmonate with Km values of 50 and 10 μm, respectively. Furthermore, 12-hydroxyjasmonate and its sulfonated derivative are shown to be naturally occurring inA. thaliana. The exogenous application of methyljasmonate to A. thaliana plants led to increased levels of both metabolites, whereas treatment with 12-hydroxyjasmonate led to increased level of 12-hydroxyjasmonate sulfate without affecting the endogenous level of jasmonic acid. AtST2a expression was found to be induced following treatment with methyljasmonate and 12-hydroxyjasmonate. In contrast, the expression of the methyljasmonate-responsive gene Thi2.1, a marker gene in plant defense responses, is not induced upon treatment with 12-hydroxyjasmonate indicating the existence of independent signaling pathways responding to jasmonic acid and 12-hydroxyjasmonic acid. Taken together, the results suggest that the hydroxylation and sulfonation reactions might be components of a pathway that inactivates excess jasmonic acid in plants. Alternatively, the function of AtST2a might be to control the biological activity of 12-hydroxyjasmonic acid.
A2  - 
C1  - Bioorganic Chemistry; Molecular Signal Processing
ER  - 


TY  - JOUR
ID  - 2083
TI  - Stilbenecarboxylate biosynthesis: a new function in the family of chalcone synthase-related proteins
JO  - Phytochemistry
PY  - 2003
SP  - 271-286
AU  - Eckermann, C.
AU  - Schröder, G.
AU  - Eckermann, S.
AU  - Strack, D.
AU  - Schmidt, J.
AU  - Schneider, B.
AU  - Schröder, J.
AU  - 
VL  - 62
UR  - 
DO  - 10.1016/S0031-9422(02)00554-X
AB  - Chalcone (CHS), stilbene (STS) synthases, and related proteins are key enzymes in the biosynthesis of many secondary plant products. Precursor feeding studies and mechanistic rationalization suggest that stilbenecarboxylates might also be synthesized by plant type III polyketide synthases; however, the enzyme activity leading to retention of the carboxyl moiety in a stilbene backbone has not yet been demonstrated. Hydrangea macrophylla L. (Garden Hortensia) contains stilbenecarboxylates (hydrangeic acid and lunularic acid) that are derived from 4-coumaroyl and dihydro-4-coumaroyl starter residues, respectively. We used homology-based techniques to clone CHS-related sequences, and the enzyme functions were investigated with recombinant proteins. Sequences for two proteins were obtained. One was identified as CHS. The other shared 65–70% identity with CHSs and other family members. The purified recombinant protein had stilbenecarboxylate synthase (STCS) activity with dihydro-4-coumaroyl-CoA, but not with 4-coumaroyl-CoA or other substrates. We propose that the enzyme is involved in the biosynthesis of lunularic acid. It is the first example of a STS-type reaction that does not lose the terminal carboxyl group during the ring folding to the end product. Comparisons with CHS, STS, and a pyrone synthase showed that it is the only enzyme exerting a tight control over decarboxylation reactions. The protein contains unusual residues in positions highly conserved in other CHS-related proteins, and mutagenesis studies suggest that they are important for the structure or/and the catalytic activity. The formation of the natural products in vivo requires a reducing step, and we discuss the possibility that the absence of a reductase in the in vitro reactions may be responsible for the failure to obtain stilbenecarboxylates from substrates like 4-coumaroyl-CoA.Hydrangea macrophylla (Garden Hortensia) encodes a type III polyketide synthase synthesizing the stilbenecarboxylate backbone which is the basis for the biosynthesis of many secondary products in liverworts and in higher plants.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2077
TI  - A flavonol O-methyltransferase from Catharanthus roseus performing two sequential methylations
JO  - Phytochemistry
PY  - 2003
SP  - 127-137
AU  - Cacace, S.
AU  - Schröder, G.
AU  - Wehinger, E.
AU  - Strack, D.
AU  - Schmidt, J.
AU  - Schröder, J.
AU  - 
VL  - 62
UR  - 
DO  - 10.1016/S0031-9422(02)00483-1
AB  - Protein extracts from dark-grown cell suspension cultures of Catharanthus roseus (Madagascar periwinkle) contained several O-methyltransferase (OMT) activities, including the 16-hydroxytabersonine O-methyltransferase (16HT-OMT) in indole alkaloid biosynthesis. This enzyme was enriched through several purification steps, including affinity chromatography on adenosine agarose. SDS-PAGE of the purified protein preparation revealed a protein band at the size expected for plant OMTs (38–43 kDa). Mass spectrometry indicated two dominant protein species of similar mass in this band, and sequences of tryptic peptides showed similarities to known OMTs. Homology-based RT-PCR identified cDNAs for four new OMTs. Two of these cDNAs (CrOMT2 and CrOMT4) encoded the proteins dominant in the preparation enriched for 16HT-OMT. The proteins were closely related (73% identity), but both shared only 48-53% identity with the closest relatives found in the public databases. The enzyme functions were investigated with purified recombinant proteins after cDNA expression in Escherichia coli. Unexpectedly, both proteins had no detectable 16HT-OMT activity, and CrOMT4 was inactive with all substrates investigated. CrOMT2 was identified as a flavonoid OMT that was expressed in dark-grown cell cultures and copurified with 16HT-OMT. It represented a new type of OMT that performs two sequential methylations at the 3′- and 5′-positions of the B-ring in myricetin (flavonol) and dihydromyricetin (dihydroflavonol). The resulting methylation pattern is characteristic for C. roseus flavonol glycosides and anthocyanins, and it is proposed that CrOMT2 is involved in their biosynthesis.Purification and molecular characterization of an unusual flavonoid O-dimethyltransferase that explains the 3′,5′-methylation in flavonols and anthocyanins of Madagascar periwinkle.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2076
TI  - The facile synthesis of chiral oxazoline catalysts for the diethylzinc addition to aldehydes
JO  - Tetrahedron: Asymmetry
PY  - 2003
SP  - 3291-3295
AU  - Braga, A. L.
AU  - Rubim, R. M.
AU  - Schrekker, H. S.
AU  - Wessjohann, L. A.
AU  - de Bolster, M. W.
AU  - Zeni, G.
AU  - Sehnem, J. A.
AU  - 
VL  - 14
UR  - 
DO  - 10.1016/j.tetasy.2003.08.029
AB  - A range of chiral 4-(1′-hydroxyalkyl)oxazoline catalysts can be obtained in a straightforward two step synthesis, starting from β-hydroxy amino acids like l-serine or l-threonine. Catalyst 4c forms a complex with diethylzinc, effective for the enantioselective addition to aldehydes resulting in high yields and enantiomeric excesses up to &gt;99% even with aliphatic aldehydes. In the latter case the enantiomeric excess showed a marked dependence of the aldehyde&#39;s chain length.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2075
TI  - The Role of the Side Chain in Determining Relative δ- and κ-Affinity in C5‘-Substituted Analogues of Naltrindole
JO  - J. Med. Chem.
PY  - 2003
SP  - 314-317
AU  - Black, S. L.
AU  - Jales, A. R.
AU  - Brandt, W.
AU  - Lewis, J. W.
AU  - Husbands, S. M.
AU  - 
VL  - 46
UR  - 
DO  - 10.1021/jm020997b
AB  - The role of the side chain in 5‘-substituted analogues of naltrindole has been further explored with the synthesis of series of amides, amidines, and ureas. Amidines (8, 13) had greatest selectivity for the κ receptor, as predicted from consideration of the message-address concept. It was also found that an appropriately located carbonyl group, in ureas (10) and amides (7), led to retention of affinity and antagonist potency at the δ receptor.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2074
TI  - Synthesis of N,N-disubstituted selenoamides by O/Se-exchange with selenium–Lawesson&#39;s reagent
JO  - Tetrahedron Lett.
PY  - 2003
SP  - 6911-6913
AU  - Bethke, J.
AU  - Karaghiosoff, K.
AU  - Wessjohann, L. A.
AU  - 
VL  - 44
UR  - 
DO  - 10.1016/S0040-4039(03)01690-3
AB  - The selenium analogue of Lawesson&#39;s reagent, [PhP(Se)(μ-Se)]2 is an effective reagent for synthesizing N,N-disubstituted selenoamides. The reaction is carried out under mild conditions (room temperature) and affords the selenoamide in higher yield than using other selenation reagents.The selenium analogue of Lawesson&#39;s reagent, [PhP(Se)(μ-Se)]2 is an effective reagent for synthesizing N,N-disubstituted selenoamides.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2073
TI  - Some homoisoflavonoidal compounds from Ophiopogon Japonicus Ker-gawler
JO  - Vietnam J. Chem.
PY  - 2003
SP  - 117-121
AU  - Anh, N. T. H.
AU  - Sung, T. V.
AU  - Wessjohann, L.
AU  - 
VL  - 41
UR  - http://vjs.ac.vn/index.php/vjchem/issue/view/365
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2072
TI  - Phytochemical studies of Rehmannia glutinosa rhizomes
JO  - Pharmazie
PY  - 2003
SP  - 593-595
AU  - Anh, N. T. H.
AU  - Sung, T. V.
AU  - Franke, K.
AU  - Wessjohann, L. A.
AU  - 
VL  - 58
UR  - https://www.ingentaconnect.com/contentone/govi/pharmaz/2003/00000058/00000008/art00017
AB  - 2,4-Dimethoxy-2-methyl-6H-pyran-3-one (1), a hitherto unknown natural product, and the calcium salt of rehmapicroside (2) have been isolated from rhizomes of the Vietnamese variety of Rehmannia glutinosa Libosch together with a series of known compounds: norcarotenoids (3–5), 2-formyl-5-hydroxymethylfurane (6), the iridoid rehmaglutin D (7), iridoid glycosides (8–12) and phenylethyl alcohol glycosides (13–17). Their structures were determined by mass and NMR spectroscopy.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2071
TI  - Homoisoflavonoids from Ophiopogon japonicus Ker-Gawler
JO  - Phytochemistry
PY  - 2003
SP  - 1153-1158
AU  - Anh, N. T. H.
AU  - Sung, T. V.
AU  - Porzel, A.
AU  - Franke, K.
AU  - Wessjohann, L. A.
AU  - 
VL  - 62
UR  - 
DO  - 10.1016/S0031-9422(02)00515-0
AB  - From the ethyl acetate extract of the tuberous roots of Ophiopogon japonicus (Liliaceae) eight known and five new homoisoflavonoidal compounds were isolated. The new compounds are 5,7-dihydroxy-8-methoxy-6-methyl-3-(2′-hydroxy-4′-methoxybenzyl)chroman-4-one (1), 7-hydroxy-5,8-dimethoxy-6-methyl-3-(2′-hydroxy-4′-methoxybenzyl)chroman-4-one (2), 5,7-dihydroxy-6,8-dimethyl-3-(4′-hydroxy-3′-methoxybenzyl)chroman-4-one (3), 2,5,7-trihydroxy-6,8-dimethyl-3-(3′,4′-methylenedioxybenzyl)chroman-4-one (4) and 2,5,7-trihydroxy-6,8-dimethyl-3-(4′-methoxybenzyl)chroman-4-one (5). Their structures have been elucidated by mass and NMR spectroscopy. Compounds 4 and 5 are the first isolated homoisoflavonoids with a hemiacetal function at position 2.Five new and eight known homoisoflavonoids were isolated from the tuberous roots of the medicinal plant Ophiopogon japonicus (Liliaceae) and identified by spectroscopic data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2131
TI  - Biosynthesis and Metabolism of Cyclopropane Rings in Natural Compounds
JO  - Chem. Rev.
PY  - 2003
SP  - 1625-1648
AU  - Wessjohann, L. A.
AU  - Brandt, W.
AU  - Thiemann, T.
AU  - 
VL  - 103
UR  - 
DO  - 10.1021/cr0100188
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2127
TI  - Chemical constituents of the roots of Codonopsis pilosula
JO  - Vietnam J. Chem.
PY  - 2003
SP  - 119-123
AU  - Thuy, T. T.
AU  - Sung, T. V.
AU  - Wessjohann, L.
AU  - 
VL  - 41
UR  - http://vjs.ac.vn/index.php/vjchem/issue/view/366
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2120
TI  - Lilacinone, a Red Aminobenzoquinone Pigment from Lactarius lilacinus
JO  - J. Nat. Prod.
PY  - 2003
SP  - 1402-1403
AU  - Spiteller, P.
AU  - Arnold, N.
AU  - Spiteller, M.
AU  - Steglich, W.
AU  - 
VL  - 66
UR  - 
DO  - 10.1021/np0303052
AB  - A red pigment, lilacinone (1), was isolated from fruit bodies of the toadstool Lactarius lilacinus. Its structure was established by 2D NMR and APCIMS methods. Compound 1 is a novel type of fungal aminobenzoquinone pigment and may be biosynthetically derived from three molecules of anthranilic acid.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2119
TI  - Synthesis of 6-Amino Acid Substituted Derivatives of the Highly Potent Analgesic 14-O-Methyloxymorphone
JO  - Helv. Chim. Acta
PY  - 2003
SP  - 2142-2148
AU  - Schütz, J.
AU  - Brandt, W.
AU  - Spetea, M.
AU  - Wurst, K.
AU  - Wunder, G.
AU  - Schmidhammer, H.
AU  - 
VL  - 86
UR  - 
DO  - 10.1002/hlca.200390171
AB  - The novel morphinans 13 –18 , which carry amino acid substituents at C(6), with potentially limited access to the central nervous system were prepared in two steps from 14‐O‐methyloxymorphone (5 ). Reductive amination with amino acid tert‐butyl esters gave compounds 7 –12 , which were hydrolyzed with tetrafluoroboric acid. Structure elucidation (including X‐ray analysis), preliminary μ‐opioid receptor binding studies, and calculations of pharmacokinetic parameters were carried out.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2118
TI  - An unusual amide synthetase (CouL) from the coumermycin A1 biosynthetic gene cluster from Streptomyces rishiriensis DSM 40489
JO  - Eur. J. Biochem.
PY  - 2003
SP  - 4413-4419
AU  - Schmutz, E.
AU  - Steffensky, M.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Li, S.-M.
AU  - Heide, L.
AU  - 
VL  - 270
UR  - 
DO  - 10.1046/j.1432-1033.2003.03830.x
AB  - The aminocoumarin antibiotic coumermycin A1 produced by Streptomyces rishiriensis  DSM 40489 contains two amide bonds. The biosynthetic gene cluster of coumermycin contains a putative amide synthetase gene, couL , encoding a protein of 529 amino acids. CouL was overexpressed as hexahistidine fusion protein in Escherichia coli  and purified by metal affinity chromatography, resulting in a nearly homogenous protein. CouL catalysed the formation of both amide bonds of coumermycin A1, i.e. between the central 3‐methylpyrrole‐2,4‐dicarboxylic acid and two aminocoumarin moieties. Gel exclusion chromatography showed that the enzyme is active as a monomer. The activity was strictly dependent on the presence of ATP and Mn2+ or Mg2+. The apparent K m values were determined as 26 µm  for the 3‐methylpyrrole‐2,4‐dicarboxylic acid and 44 µm  for the aminocoumarin moiety, respectively. Several analogues of the pyrrole dicarboxylic acid were accepted as substrates. In contrast, pyridine carboxylic acids were not accepted. 3‐Dimethylallyl‐4‐hydroxybenzoic acid, the acyl component in novobiocin biosynthesis, was well accepted, despite its structural difference from the genuine acyl substrate of CouL.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2114
TI  - Aromatic and pyrone polyketides synthesized by a stilbene synthase from Rheum tataricum
JO  - Phytochemistry
PY  - 2003
SP  - 313-323
AU  - Samappito, S.
AU  - Page, J. E.
AU  - Schmidt, J.
AU  - De-Eknamkul, W.
AU  - Kutchan, T. M.
AU  - 
VL  - 62
UR  - 
DO  - 10.1016/S0031-9422(02)00545-9
AB  - A cDNA encoding a stilbene synthase, RtSTS, was isolated from the rhizomes of Tatar rhubarb, Rheum tataricum L. (Polygonaceae), a medicinal plant containing stilbenes and other polyketides. Recombinant RtSTS was expressed in E. coli and assayed with acetyl-coenzyme A (CoA), n-butyryl-CoA, isovaleryl-CoA, n-hexanoyl-CoA, cinnamoyl-CoA and p-coumaroyl-CoA as primers of polyketide synthesis. RtSTS synthesized resveratrol and a trace amount of naringenin chalcone from p-coumaroyl-CoA, supporting the enzyme&#39;s identification as a resveratrol-type stilbene synthase (EC 2.3.1.95). Bis-noryangonin and p-coumaroyl triacetic acid lactone (CTAL)-type pyrones were observed in minor amounts in the reaction with p-coumaroyl-CoA and as major products with cinnamoyl CoA. As well, such pyrones, and not aromatic polyketides, were identified as the only products in assays with aliphatic and benzoyl CoA esters. Acetonyl-4-hydroxy-2-pyrone, a pyrone synthesized from acetyl-CoA, was identified as a new product of a stilbene synthase. Using Northern blot analysis, RtSTS transcript was found to be highly expressed in R. tataricum rhizomes, with low transcript levels also present in young leaves. This expression pattern correlated with the occurrence of resveratrol, which was detected in higher amounts in R. tataricum rhizomes compared with leaves and petioles using HPLC. Few stilbene synthases have been found in plants, and the identification of RtSTS provides additional sequence and catalytic information with which to study the evolution of plant polyketide synthases.A cDNA encoding a plant polyketide synthase was isolated from Rheum tataricum and functionally charactarized as a resveratrol-forming stilbene synthase.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2113
TI  - Second generation epothilones and their biological properties
JO  - Clin. Cancer Res.
PY  - 2003
SP  - 6137
AU  - Richter, W. G.
AU  - Cappi, M. W.
AU  - Henkel, B.
AU  - Hess, S.
AU  - Surivet, J. P.
AU  - Baeschlin, D.
AU  - Hubschwerlen, C.
AU  - Höfle, G.
AU  - Wessjohann, L. A.
AU  - Eichelberger, U.
AU  - 
VL  - 9
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2112
TI  - Electrospray tandem mass spectrometric investigations of morphinans
JO  - J. Am. Soc. Mass Spectrom.
PY  - 2003
SP  - 1262-1269
AU  - Raith, K.
AU  - Neubert, R.
AU  - Poeaknapo, C.
AU  - Boettcher, C.
AU  - Zenk, M. H.
AU  - Schmidt, J.
AU  - 
VL  - 14
UR  - 
DO  - 10.1016/S1044-0305(03)00539-7
AB  - In this study positive ESI tandem mass spectra of the [M+H]+ ions of morphinan alkaloids obtained using an ion trap MS were compared with those from a triple quadrupole MS. This allows to assess the differences of the tandem-in-time versus the tandem-in-space principle, often hampering the development of ESI MS/MS libraries. Fragmentation pathways and possible fragment ion structures were discussed. In order to obtain elemental composition, accurate mass measurements were performed. According to the MS/MS fragmentation pathway, the investigated compounds can be grouped into 4 subsets: (1) morphine and codeine, (2) morphinone, codeinone, and neopinone, (3) thebaine and oripavine, (4) salutaridine and salutaridinol. Salutaridinol-7-O-acetate shows a different fragmentation behavior because of the favored loss of acetic acid. Although most fragment ions occur in both ion trap and triple quad tandem mass spectra, some are exclusively seen in either type. For triple quad, quadrupole time-of-flight and FT-ICR MS/MS, the base peak of morphine results from an ion at m/z 165 that contains neither nitrogen nor oxygen. This ion is not found in ion trap MS/MS, but in subsequential MS3 and MS4.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2108
TI  - (R,S)-Reticuline 7-O-methyltransferase and (R,S)-norcoclaurine 6-O-methyltransferase of Papaver somniferum-cDNA cloning and characterization of methyl transfer enzymes of alkaloid biosynthesis in opium poppy
JO  - Plant J.
PY  - 2003
SP  - 808-819
AU  - Ounaroon, A.
AU  - Decker, G.
AU  - Schmidt, J.
AU  - Lottspeich, F.
AU  - Kutchan, T. M.
AU  - 
VL  - 36
UR  - 
DO  - 10.1046/j.1365-313X.2003.01928.x
AB  - S‐Adenosyl‐l ‐methionine:(R,S )‐reticuline 7‐O‐methyltransferase converts reticuline to laudanine in tetrahydrobenzylisoquinoline biosynthesis in the opium poppy Papaver somniferum . This enzyme activity has not yet been detected in plants. A proteomic analysis of P. somniferum  latex identified a gel spot that contained a protein(s) whose partial amino acid sequences were homologous to those of plant O‐methyltransferases. cDNA was amplified from P. somniferum  RNA by reverse transcription PCR using primers based on these internal amino acid sequences. Recombinant protein was then expressed in Spodoptera frugiperda  Sf9 cells in a baculovirus expression vector. Steady‐state kinetic measurements with one heterologously expressed enzyme and mass spectrometric analysis of the enzymatic products suggested that this unusual enzyme is capable of carrying through sequential O‐methylations on the isoquinoline and on the benzyl moiety of several substrates. The tetrahydrobenzylisoquinolines (R )‐reticuline (4.2 sec−1 mm −1), (S )‐reticuline (4.5 sec−1 mm −1), (R )‐protosinomenine (1.7 sec−1 mm −1), and (R,S )‐isoorientaline (1.4 sec−1 mm −1) as well as guaiacol (5.9 sec−1 mm −1) and isovanillic acid (1.2 sec−1 mm −1) are O‐methylated by the enzyme with the ratio k cat/K  m shown in parentheses. A P. somniferum  cDNA encoding (R,S )‐norcoclaurine 6‐O‐methyltransferase was similarly isolated and characterized. This enzyme was less permissive, methylating only (R,S )‐norcoclaurine (7.4 sec−1 mm −1), (R )‐norprotosinomenine (4.1 sec−1 mm −1), (S )‐norprotosinomenine (4.0 sec−1 mm −1) and (R,S )‐isoorientaline (1.0 sec−1 mm −1). A phylogenetic comparison of the amino acid sequences of these O‐methyltransferases to those from 28 other plant species suggests that these enzymes group more closely to isoquinoline biosynthetic O‐methyltransferases from Coptis japonica  than to those from Thalictrum tuberosum  that can O‐methylate both alkaloid and phenylpropanoid substrates.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2197
TI  - Genetic analysis of the biosynthesis of the pyrrole and carbamoyl moieties of coumermycin A1 and novobiocin
JO  - Mol. Gen. Genomics
PY  - 2002
SP  - 387-396
AU  - Xu, H.
AU  - Wang, Z.-X.
AU  - Schmidt, J.
AU  - Heide, L.
AU  - Li, S.-M.
AU  - 
VL  - 268
UR  - 
DO  - 10.1007/s00438-002-0759-1
AB  - The aminocoumarin antibiotic coumermycin A1 contains a central and two terminal pyrrole moieties. The coumermycin gene cluster in Streptomyces rishiriensis contains three genes (couN3, couN4 and couN5) that show sequence similarity to genes involved in the biosynthesis of the pyrrole moieties of pyoluteorin in Pseudomonas fluorescens and of undecylprodiginine in S. coelicolor. The gene couN3, which codes for a putative L-prolyl-S-PCP dehydrogenase, and the gene couN4, which encodes a putative L-prolyl-AMP ligase, were disrupted using in-frame deletion and insertional inactivation, respectively. HPLC analysis of culture extracts showed that formation of the two terminal pyrrole moieties was abolished in the couN3 - und couN4 - mutants. The mutants accumulated coumermycin D, which contains only the central pyrrole moiety. This result not only confirmed the involvement of couN3 and couN4 in the biosynthesis of the terminal pyrrole-2-carboxylic acid moieties of coumermycin A1, but also indicated, for the first time, that the central 3-methylpyrrole-2,4-dicarboxylic acid unit of the coumermycins is formed by a biosynthetic pathway that differs from that used to assemble the terminal pyrrole moieties. novN, a putative carbamoyl transferase gene from the gene cluster for novobiocin biosynthesis in S. spheroides was expressed in the couN3 - mutant. This led to the formation of bis-carbamoylated coumermycin D, a novel compound of the coumermycin series.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2193
TI  - Synthesis of 2,24-Diepicastasterone and 3,24-Diepicastasterone as Potential Brassinosteroid Metabolites of the Cockroach Periplaneta americana
JO  - Collect. Czech. Chem. Commun.
PY  - 2002
SP  - 91-102
AU  - Voigt, B.
AU  - Porzel, A.
AU  - Adam, G.
AU  - Golsch, D.
AU  - Adam, W.
AU  - Wagner, C.
AU  - Merzweiler, K.
AU  - 
VL  - 67
UR  - 
DO  - 10.1135/cccc20020091
AB  - Investigations of the metabolic conversion of the phytohormone 24-epicastasterone (1) in the cockroach Periplaneta americana (L.) required the synthesis of 2,24-diepicastasterone (4), 3,24-diepicastasterone (7b) and 2-dehydro-3,24-diepicastasterone (9) as reference standards. 2,24-Diepicastasterone (4) was synthesized from 2α,3α-epoxy derivative 2 as well as from the 2β,3β-epoxy-22,23-diol 3 by acid-catalyzed water addition to the epoxy function leading to the desired 2β,3α-trans functionality. 3,24-Diepicastasterone (7b) was prepared by NaBH4-reduction of the 3-oxo derivative 6. Upon deprotection conditions from the ketol acetonides 6 and 8 in both cases 2-dehydro-3,24-diepicastasterone (9) was obtained. The structure of 2,24-diepicastasterone (4) was confirmed by X-ray analysis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2187
TI  - Interactions between sterol biosynthesis genes in embryonic development of Arabidopsis
JO  - Plant J.
PY  - 2002
SP  - 61-73
AU  - Schrick, K.
AU  - Mayer, U.
AU  - Martin, G.
AU  - Bellini, C.
AU  - Kuhnt, C.
AU  - Schmidt, J.
AU  - Jürgens, G.
AU  - 
VL  - 31
UR  - 
DO  - 10.1046/j.1365-313X.2002.01333.x
AB  - The sterol biosynthesis pathway of Arabidopsis  produces a large set of structurally related phytosterols including sitosterol and campesterol, the latter being the precursor of the brassinosteroids (BRs). While BRs are implicated as phytohormones in post‐embryonic growth, the functions of other types of steroid molecules are not clear. Characterization of the fackel  (fk ) mutants provided the first hint that sterols play a role in plant embryogenesis. FK  encodes a sterol C‐14 reductase that acts upstream of all known enzymatic steps corresponding to BR biosynthesis mutants. Here we report that genetic screens for fk‐like seedling and embryonic phenotypes have identified two additional genes coding for sterol biosynthesis enzymes: CEPHALOPOD (CPH), a C‐24 sterol methyl transferase, and HYDRA1 (HYD1), a sterol C‐8,7 isomerase. We describe genetic interactions between cph , hyd1  and fk , and studies with 15‐azasterol, an inhibitor of sterol C‐14 reductase. Our experiments reveal that FK  and HYD1  act sequentially, whereas CPH  acts independently of these genes to produce essential sterols. Similar experiments indicate that the BR biosynthesis gene DWF1  acts independently of FK , whereas BR receptor gene BRI1  acts downstream of FK  to promote post‐embryonic growth. We found embryonic patterning defects in cph  mutants and describe a GC–MS analysis of cph  tissues which suggests that steroid molecules in addition to BRs play critical roles during plant embryogenesis. Taken together, our results imply that the sterol biosynthesis pathway is not a simple linear pathway but a complex network of enzymes that produce essential steroid molecules for plant growth and development.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2186
TI  - In Situ Formation of Allyl Ketones via Hiyama−Nozaki Reactions Followed by a Chromium-Mediated Oppenauer Oxidation
JO  - J. Org. Chem.
PY  - 2002
SP  - 1975-1981
AU  - Schrekker, H. S.
AU  - de Bolster, M. W. G.
AU  - Orru, R. V. A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 67
UR  - 
DO  - 10.1021/jo001750u
AB  - In Hiyama−Nozaki reactions of allylchromium with aldehydes the expected products are homoallylalcohols. However, oxidation products derived from these, predominantly allyl ketones, can be common side products. This can be explained by an Oppenauer−(Meerwein−Ponndorf−Verley)-type mechanism (OMPV-reaction). The amount of oxidation is strongly dependent on the substitution pattern of the reaction partners and the reaction conditions. An appropriate choice of these can lead to preferential formation of ketones instead of the alcohols. In addition to its synthetic usefulness, the oxidation−reduction equilibrium is of the utmost importance for the design of enantioselective Hiyama−Nozaki reactions because it is also a potential racemization pathway.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2185
TI  - Evidence for the direct 2β‐ and 3β‐hydroxylation of [2H2]GA20‐13‐O‐[6′‐2H2]glucoside in seedlings of Phaseolus coccineus
JO  - Physiol. Plant.
PY  - 2002
SP  - 144-147
AU  - Schneider, G.
AU  - Fuchs, P.
AU  - Schmidt, J.
AU  - 
VL  - 116
UR  - 
DO  - 10.1034/j.1399-3054.2002.1160202.x
AB  - [17‐2H2]GA20‐13‐O‐[6′‐2H2]glucoside was synthesized and applied to seedlings of Phaseolus coccineus  L. After incubation for 72 h the conjugate metabolites were purified and shown by LC‐ESI‐tandem‐MS and GC‐MS to be [17‐2H2]GA1‐13‐O‐[6′‐2H2]glucoside and [17‐2H2]GA29‐13‐O‐[6′‐2H2]glucoside. This is the first evidence for the conversion of intact GA‐O‐glucosides, and represents an additional metabolic pathway of the gibberellin metabolism in P. coccineus  L. The results indicate that intact GA‐O‐glucosides are accepted by 2‐ and 3‐oxidases in the plant.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2182
TI  - Molecular characterization of root-specific chalcone synthases from Cassia alata
JO  - Planta
PY  - 2002
SP  - 64-71
AU  - Samappito, S.
AU  - Page, J.
AU  - Schmidt, J.
AU  - De-Eknamkul, W.
AU  - Kutchan, T. M.
AU  - 
VL  - 216
UR  - 
DO  - 10.1007/s00425-002-0872-8
AB  - Three cDNAs encoding very similar but unique isoforms of chalcone synthase (EC 2.3.1.74) were isolated from a cDNA library prepared from RNA from root tissue of the Thai medicinal plant Cassia alata L. (ringworm bush, Leguminosae). Gene transcript for these three type-III polyketide synthases was found to accumulate predominantly in roots. The heterologously expressed enzymes accepted acetyl-, n-butyryl-, isovaleryl-, n-hexanoyl-, benzoyl-, cinnamoyl-, and p-coumaroyl-CoA as starter molecules and together with the co-substrate malonyl-CoA, formed multiple products. With the exception of the assay in which acetyl-CoA was used as the starter molecule, all substrates yielded a phloroglucinol derivative resulting from three sequential condensations of acetate units derived from three malonyl-CoA decarboxylations. Every substrate tested also produced two pyrone derivatives, one resulting from two acetate unit condensations (a bis-noryangonin-type pyrone derailment product) and one resulting from three acetate unit condensations (a 4-coumaroyltriacetic acid lactone-type pyrone derailment). C. alata accumulates the flavonoids quercetin, naringenin and kaempferol in roots, suggesting that the in planta function of these enzymes is the biosynthesis of root flavonoids.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2178
TI  - Apotirucallane triterpenoids from Luvunga sarmentosa (Rutaceae)
JO  - Phytochemistry
PY  - 2002
SP  - 747-754
AU  - Lien, T. P.
AU  - Kamperdick, C.
AU  - Schmidt, J.
AU  - Adam, G.
AU  - Sung, T. V.
AU  - 
VL  - 60
UR  - 
DO  - 10.1016/S0031-9422(02)00156-5
AB  - The leaves of Luvunga sarmentosa (Bl.) Kurz. yielded eight apotirucallane triterpenoids named luvungins A–G, and 1α-acetoxyluvungin A. Characteristic of the structure are the seven-membered lactone-ring A, the α-hydroxyl or α-acetoxyl group at C-7 and an oxygen bridge in the side chain giving five-, six- or seven-membered rings, respectively. Because of a hemiacetal function at C-21, luvungin C occurred as a mixture of 21-epimers. The structures have been elucidated on the basis of MS and NMR spectral data. In addition, two known coumarins ostruthin (6-geranyl-7-hydroxycoumarin) and 8-geranyl-7-hydroxycoumarin as well as five known triterpenes friedelin, flindissone, melianone, niloticin and limonin were isolated.The leaves of Luvunga sarmentosa (Bl.) Kurz. yielded eight apotirucallane triterpenoids named luvungins A–G and 1α-acetoxyluvungin A. Characteristic for the luvungins were the seven-membered lactone-ring A, the α-hydroxyl or α-acetoxyl group at C-7 and an oxygen bridge in the side chain giving five-, six- or seven-membered rings.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2177
TI  - Methyltransferase genes in Streptomyces rishiriensis: new coumermycin derivatives from gene-inactivation experiments
JO  - Microbiol.
PY  - 2002
SP  - 3317-3326
AU  - Li, S.-M.
AU  - Westrich, L.
AU  - Schmidt, J.
AU  - Kuhnt, C.
AU  - Heide, L.
AU  - 
VL  - 148
UR  - 
DO  - 10.1099/00221287-148-10-3317
AB  - The coumarin antibiotic coumermycin A1 contains at least eight methyl groups, presumably derived from S-adenosylmethionine. Two putative methyltransferase genes, couO and couP, of the coumermycin A1 biosynthetic gene cluster were inactivated by in-frame deletion. In the resulting mutants, coumermycin A1 production was abolished. New coumermycin derivatives were accumulated instead, and were identified by HPLC-MS using selected reaction monitoring via electrospray ionization. couO mutants accumulated a coumermycin derivative lacking the methyl groups at C-8 of the characteristic aminocoumarin rings, whereas in the couP mutant a coumermycin derivative lacking the methyl groups at the 4-hydroxyl groups of the two deoxysugar moieties was identified. These results provided evidence that couO encodes a C-methyltransferase responsible for the transfer of a methyl group to C-8 of the aminocoumarin ring, and couP an O-methyltransferase for methylation of 4-OH of the sugar in the biosynthesis of coumermycin A1, respectively. C-methylation of the aminocoumarin ring is considered as an early step of coumermycin biosynthesis. Nevertheless, the intermediates with the non-methylated aminocoumarin ring were accepted by the enzymes catalysing the subsequent steps of the pathway. The new, demethylated secondary metabolites were produced in an amount at least as high as that of coumermycin A1 in the wild-type.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2175
TI  - Selective Inhibition of the Collagenolytic Activity of Human Cathepsin K by Altering Its S2 Subsite Specificity
JO  - Biochemistry
PY  - 2002
SP  - 8447-8454
AU  - Lecaille, F.
AU  - Choe, Y.
AU  - Brandt, W.
AU  - Li, Z.
AU  - Craik, C. S.
AU  - Brömme, D.
AU  - 
VL  - 41
UR  - 
DO  - 10.1021/bi025638x
AB  - The primary specificity of papain-like cysteine proteases (family C1, clan CA) is determined by S2−P2 interactions. Despite the high amino acid sequence identities and structural similarities between cathepsins K and L, only cathepsin K is capable of cleaving interstitial collagens in their triple helical domains. To investigate this specificity, we have engineered the S2 pocket of human cathepsin K into a cathepsin L-like subsite. Using combinatorial fluorogenic substrate libraries, the P1−P4 substrate specificity of the cathepsin K variant, Tyr67Leu/Leu205Ala, was determined and compared with those of cathepsins K and L. The introduction of the double mutation into the S2 subsite of cathepsin K rendered the unique S2 binding preference of the protease for proline and leucine residues into a cathepsin L-like preference for bulky aromatic residues. Homology modeling and docking calculations supported the experimental findings. The cathepsin L-like S2 specificity of the mutant protein and the integrity of its catalytic site were confirmed by kinetic analysis of synthetic di- and tripeptide substrates as well as pH stability and pH activity profile studies. The loss of the ability to accept proline in the S2 binding pocket by the mutant protease completely abolished the collagenolytic activity of cathepsin K whereas its overall gelatinolytic activity remained unaffected. These results indicate that Tyr67 and Leu205 play a key role in the binding of proline residues in the S2 pocket of cathepsin K and are required for its unique collagenase activity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2173
TI  - Accumulation of tyrosol glucoside in transgenic potato plants expressing a parsley tyrosine decarboxylase
JO  - Phytochemistry
PY  - 2002
SP  - 683-689
AU  - Landtag, J.
AU  - Baumert, A.
AU  - Degenkolb, T.
AU  - Schmidt, J.
AU  - Wray, V.
AU  - Scheel, D.
AU  - Strack, D.
AU  - Rosahl, S.
AU  - 
VL  - 60
UR  - 
DO  - 10.1016/S0031-9422(02)00161-9
AB  - As part of the response to pathogen infection, potato plants accumulate soluble and cell wall-bound phenolics such as hydroxycinnamic acid tyramine amides. Since incorporation of these compounds into the cell wall leads to a fortified barrier against pathogens, raising the amounts of hydroxycinnamic acid tyramine amides might positively affect the resistance response. To this end, we set out to increase the amount of tyramine, one of the substrates of the hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)-transferase reaction, by placing a cDNA encoding a pathogen-induced tyrosine decarboxylase from parsley under the control of the 35S promoter and introducing the construct into potato plants via Agrobacterium tumefaciens-mediated transformation. While no alterations were observed in the pattern and quantity of cell wall-bound phenolic compounds in transgenic plants, the soluble fraction contained several new compounds. The major one was isolated and identified as tyrosol glucoside by liquid chromatography–electrospray ionization–high resolution mass spectrometry and NMR analyses. Our results indicate that expression of a tyrosine decarboxylase in potato does not channel tyramine into the hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)-transferase reaction but rather unexpectedly, into a different pathway leading to the formation of a potential storage compound.Expression of a parsley tyrosine decarboxylase in potato unexpectedly channels tyramine into a pathway leading to the formation of tyrosol glucoside.
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions
ER  - 


TY  - JOUR
ID  - 2171
TI  - Synthesis and crystal structure of [26,27-2H6] 24-epi-cathasterone
JO  - J. Chem. Soc., Perkin Trans. 1
PY  - 2002
SP  - 2022-2027
AU  - Kolbe, A.
AU  - Fuchs, P.
AU  - Porzel, A.
AU  - Baumeister, U.
AU  - Kolbe, A.
AU  - Adam, G.
AU  - 
VL  - 2002
UR  - 
DO  - 10.1039/B203323B
AB  - The first synthesis of [26,27-2H6]24-epi-cathasterone 8via (20S)-3β-acetoxy-6,6-(ethylenedioxy)-20-formyl-5α-pregnane 5 starting from stigmasterol is described. The aldehyde 5 was alkylated with lithium butyldimethyl-(E)-2,3-dimethyl[3,3,3,4,4,4-2H6]butenylaluminate 6 prepared from 3-[2H3]methyl[4,4,4-2H3]but-1-yne. The structure was determined using spectral data and X-ray crystallographic analysis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2170
TI  - Syntheses of Dexamethasone Conjugates of the Phytohormones Gibberellin A3 and 24-Epicastasterone
JO  - Collect. Czech. Chem. Commun.
PY  - 2002
SP  - 103-114
AU  - Kolbe, A.
AU  - Kramell, R.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Schneider, G.
AU  - Adam, G.
AU  - 
VL  - 67
UR  - 
DO  - 10.1135/cccc20020103
AB  - The syntheses of N-[10-(9α-fluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxamido)decyl]gibberellamide (7) and 6-[({N-[10-(9α-fluoro-11β,17α-dihydroxy- 16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxamido)decyl]carbamoyl}methoxy)imino]-24-epicastasterone (10) are described. [(Benzotriazol-1-yl)oxy]bis(pyrrolidin-1-yl)methylium hexafluorophosphate (HBPyU) was used as the coupling agent for the reaction of gibberellic acid as well as of 24-epicastasterone-O-(carboxymethyl)oxime with N-(10-aminodecyl)- 9α-fluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxamide (4). The gibberellic acid conjugate 7 was also synthesised by the coupling of succinimidyl gibberellate 6 with amine 4.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2166
TI  - Diazabicyclononanones, a potent class of kappa opioid analgesics
JO  - Farmaco
PY  - 2002
SP  - 531-534
AU  - Holzgrabe, U.
AU  - Cambareri, A.
AU  - Kuhl, U.
AU  - Siener, T.
AU  - Brandt, W.
AU  - Straßburger, W.
AU  - Friderichs, E.
AU  - Englberger, W.
AU  - Kögel, B.
AU  - Haurand, M.
AU  - 
VL  - 57
UR  - 
DO  - 10.1016/S0014-827X(02)01243-0
AB  - The 1,5-dimethyl 3,7-diaza-3,7-dimethyl-9-oxo-2,4-di-2-pyridine-bicyclo[3.3.1]nonane-1,5-dicarboxylate, HZ2, has a high and selective affinity for the kappa opioid receptor and an antinociceptive activity comparable to morphine. In addition, it is characterized by a long duration of action and a high oral bioavailability. QSAR studies within series of kappa agonists revealed a chair-boat conformation of a double protonated HZ2 characterized by an almost parallel orientation of the C9 carbonyl group and the N7-H group and at least one aromatic ring to be the pharmacophoric arrangement. Structural variations showed that the pyridine rings in 2 and 4 position can be replaced with p-methoxy-, m-hydroxy- and m-fluoro-substituted phenyl rings. However, all other substituents have to be kept the same for a high affinity to the kappa receptor.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2165
TI  - Diazabicyclononanones, a new class of opioid-type analgesics
JO  - Sci. Cult.
PY  - 2002
SP  - 1-4
AU  - Holzgrabe, U.
AU  - Friderichs, E.
AU  - Englberger, W.
AU  - Strassberger, W.
AU  - Maurand, M.
AU  - Brandt, W.
AU  - Camberri, A.
AU  - Kuhl, U.
AU  - Siener, T.
AU  - 
VL  - 68
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2160
TI  - (E)-4-Hydroxy-3-methylbut-2-enyl Diphosphate: An Intermediate in the Formation of Terpenoids in Plant Chromoplasts
JO  - Angew. Chem. Int. Ed.
PY  - 2002
SP  - 2604-2607
AU  - Gao, W.
AU  - Loeser, R.
AU  - Raschke, M.
AU  - Dessoy, M. A.
AU  - Fulhorst, M.
AU  - Alpermann, H.
AU  - Wessjohann, L. A.
AU  - Zenk, M. H.
AU  - 
VL  - 41
UR  - 
DO  - 10.1002/1521-3773(20020715)41:14&lt;2604::AID-ANIE2604&gt;3.0.CO;2-S
AB  - The missing link  in the new deoxyxylulose phosphate metabolic pathway leading to the biosynthesis of plant terpenoids has been identified. The intermediate between the cyclic diphosphate 1  and the basic isoprenoid building blocks dimethylallyl diphosphate and isopentenyl diphosphate has been shown for the first time to be (E )‐4‐hydroxy‐3‐methylbut‐2‐enyl diphosphate (2 ) by incorporation of tritium‐labeled 2  into phytoene.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2159
TI  - Cloning and analysis of the simocyclinone biosynthetic gene cluster of Streptomyces antibioticus Tü 6040
JO  - Arch. Microbiol.
PY  - 2002
SP  - 102-114
AU  - Galm, U.
AU  - Schimana, J.
AU  - Fiedler, H.-P.
AU  - Schmidt, J.
AU  - Li, S.-M.
AU  - Heide, L.
AU  - 
VL  - 178
UR  - 
DO  - 10.1007/s00203-002-0429-z
AB  - The biosynthetic gene cluster of the aminocoumarin antibiotic simocyclinone D8 was cloned by screening a cosmid library of Streptomyces antibioticus Tü 6040 with a heterologous probe from a gene encoding a cytochrome P450 enzyme involved in the biosynthesis of the aminocoumarin antibiotic novobiocin. Sequence analysis of a 39.4-kb region revealed the presence of 38 ORFs. Six of the identified ORFs showed striking similarity to genes from the biosynthetic gene clusters of the aminocoumarin antibiotics novobiocin and coumermycin A1. Simocyclinone also contains an angucyclinone moiety, and 12 of the ORFs showed high sequence similarity to biosynthetic genes of other angucyclinone antibiotics. Possible functions within the biosynthesis of simocyclinone D8 could be assigned to 23 ORFs by comparison with sequences in GenBank. Experimental proof for the function of the identified gene cluster was provided by a gene inactivation experiment, which resulted in the abolishment of the formation of the aminocoumarin moiety of simocyclinone. Feeding of the mutant with the aminocoumarin moiety of novobiocin led to a new, artificial simocyclinone derivative.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2158
TI  - Flavone-coumarin hybrids from Gnidia socotrana
JO  - Phytochemistry
PY  - 2002
SP  - 873-878
AU  - Franke, K.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - 
VL  - 61
UR  - 
DO  - 10.1016/S0031-9422(02)00358-8
AB  - Phytochemical investigation of leaves and twigs of Gnidia socotrana (Balf. f.) Gilg (Thymelaeaceae), a plant occurring endemically on Socotra Island (Yemen), afforded six novel natural products: two compounds consisting of a flavone and a coumarin moiety connected by a C–C linkage, 7,7′-dihydroxy-3,8′-biscoumarin and three substances with the rare spiro-bis-γ-lactone structure. The structures were elucidated on the basis of their spectroscopic data.Two flavone-coumarin hybrids representing a new structural type of natural products as well as a biscoumarin and three spiro-bis-γ-lactones were isolated from leaves and twigs of Gnidia socotrana (Thymelaeaceae) and identified by spectroscopic data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2154
TI  - Occurrence and Localization of Apocarotenoids in Arbuscular Mycorrhizal Plant Roots
JO  - Plant Cell Physiol.
PY  - 2002
SP  - 256-265
AU  - Fester, T.
AU  - Hause, B.
AU  - Schmidt, D.
AU  - Halfmann, K.
AU  - Schmidt, J.
AU  - Wray, V.
AU  - Hause, G.
AU  - Strack, D.
AU  - 
VL  - 43
UR  - 
DO  - 10.1093/pcp/pcf029
AB  - The core structure of the yellow pigment from arbuscular mycorrhizal (AM) maize roots contains the apocarotenoids mycorradicin (an acyclic C14 polyene) and blumenol C cellobioside (a C13 cyclohexenone diglucoside). The pigment seems to be a mixture of different esterification products of these apocarotenoids. It is insoluble in water and accumulates as hydrophobic droplets in the vacuoles of root cortical cells. Screening 58 species from 36 different plant families, we detected mycorradicin in mycorrhizal roots of all Liliopsida analyzed and of a considerable number of Rosopsida, but also species were found in which mycorradicin was undetectable in mycorrhizal roots. Kinetic experiments and microscopic analyses indicate that accumulation of the yellow pigment is correlated with the concomitant degradation of arbuscules and the extensive plastid network covering these haustorium-like fungal structures. The role of the apocarotenoids in mycorrhizal roots is still unknown. The potential C40 carotenoid precursors, however, are more likely to be of functional importance in the development and functioning of arbuscules.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2152
TI  - Study of Chaperone-Like Activity of Human Haptoglobin: Conformational Changes under Heat Shock Conditions and Localization of Interaction Sites
JO  - Biol. Chem.
PY  - 2002
SP  - 1667-1676
AU  - Ettrich, R.
AU  - Brandt, W.
AU  - Kopecký, V.
AU  - Baumruk, V.
AU  - Hofbauerová, K.
AU  - Pavlícek, Z.
AU  - 
VL  - 383
UR  - 
DO  - 10.1515/BC.2002.187
AB  - With respect to the mechanism of chaperonelike activity, we examined the behavior of haptoglobin under heat shock conditions. Secondary structure changes during heat treatment were followed by circular dichroism, Raman and infrared spectroscopy. A model of the haptoglobin tetramer, based on its sequence homology with serine proteases and the CCP modules, has been proposed. Sequence regions responsible for the chaperonelike activity were not fully identical with the region that takes part in formation of the hemoglobinhaptoglobin complex. We can postulate the presence of at least two different chaperonebinding sites on each haptoglobin heavy chain.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2141
TI  - Facile and practical enantioselective synthesis of propargylic alcohols by direct addition of alkynes to aldehydes catalyzed by chiral disulfide–oxazolidine ligands
JO  - Tetrahedron
PY  - 2002
SP  - 10413-10416
AU  - Braga, A. L.
AU  - Appelt, H. R.
AU  - Silveira, C. C.
AU  - Wessjohann, L. A.
AU  - Schneider, P. H.
AU  - 
VL  - 58
UR  - 
DO  - 10.1016/S0040-4020(02)01420-5
AB  - The enantioselective alkynylation reaction of aldehydes with alkynes and diethylzinc, catalyzed by chiral disulfide–oxazolidine ligands, provides a simple, practical and inexpensive method to access chiral propargylic alcohols in good yields and satisfactory ee&#39;s.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2140
TI  - Chiral diselenide ligands for the asymmetric copper-catalyzed conjugate addition of Grignard reagents to enones
JO  - Tetrahedron Lett.
PY  - 2002
SP  - 7329-7331
AU  - Braga, A. L.
AU  - Silva, S. J. N.
AU  - Lüdtke, D. S.
AU  - Drekener, R. L.
AU  - Silveira, C. C.
AU  - Rocha, J. B. T.
AU  - Wessjohann, L. A.
AU  - 
VL  - 43
UR  - 
DO  - 10.1016/S0040-4039(02)01713-6
AB  - The copper-catalyzed conjugate addition of Grignard reagents to enones in the presence of chiral diselenide oxazoline ligands has been studied and found to provide good yields and useful levels of asymmetric induction.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2138
TI  - Coumarins give misleading absorbance with Ellmanâ€™s reagent suggestive of thiol conjugates
JO  - Analyst
PY  - 2002
SP  - 333-336
AU  - Berlich, M.
AU  - Menge, S.
AU  - Bruns, I.
AU  - Schmidt, J.
AU  - Schneider, B.
AU  - Krauss, G.-J.
AU  - 
VL  - 127
UR  - 
DO  - 10.1039/B110988J
AB  - In the course of a screening for phytochelatins in cadmium-exposed bryophytes in the terrestrial mosses Polytrichum formosum and Atrichum undulatum we detected compounds with absorption properties and retention times similar to phytochelatins when applying the commonly used standard method RP-HPLC and post-column derivatization with thiol-specific DTNB (Ellman) reagent. Moreover, as with phytochelatins known in other plants, the concentrations of these compounds increased slightly after Cd stress. The concentration of the precursor glutathione (γ-ECG), however, increased in the presence of Cd. In order to verify the identity of these putative phytochelatins we performed LC-ESI-MS analyses as well as 1H NMR on extracts from P. formosum and A. undulatum. Spectroscopic investigations indicated that the detected compounds were neither phytochelatins nor other thiol compounds. From the results of HPLC-1H NMR and mass spectrometry we concluded that at least one of these substances was a coumarin, probably a 5,8-dihydroxy-7-methoxycoumarin-5-β-glucopyranoside, which has already been described for A. undulatum and P. formosum. The results of our investigations prove that under the basic pH conditions essential for the Ellman test for thiol compounds, coumarins show comparable UV/VIS absorption properties. Therefore, a positive post-column Ellman reaction cannot unambiguously prove the presence of thiol-containing compounds in plants.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2136
TI  - The iridois and iridoid glycosid from the Rehmanuia glutinosa Rhizome
JO  - Vietnam J. Chem.
PY  - 2002
SP  - 17-22
AU  - Anh, N. T. H.
AU  - Sung, T. V.
AU  - Wessjohann, L.
AU  - Adam, G.
AU  - 
VL  - 40
UR  - vjs.ac.vn/index.php/vjchem/issue/view/362
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2135
TI  - Some hydroxycinnamic acid esters of phenylethyl alcohol glycosides from Rehmannia glutinosa Libosch
JO  - Vietnam J. Chem.
PY  - 2002
SP  - 175-179
AU  - Anh, N. T. H.
AU  - Sung, T. V.
AU  - Wessjohann, L. A.
AU  - Adam, G.
AU  - 
VL  - 40
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2146
TI  - Chemotaxonomy of the tribe Antidesmeae (Euphorbiaceae): antidesmone and related compounds
JO  - Phytochemistry
PY  - 2002
SP  - 489-496
AU  - Buske, A.
AU  - Schmidt, J.
AU  - Hoffmann, P.
AU  - 
VL  - 60
UR  - 
DO  - 10.1016/S0031-9422(02)00117-6
AB  - Selected species of the tribe Antidesmeae (Euphorbiaceae, subfamily Phyllanthoideae) have been screened for antidesmone occurrence and its content by quantitative HPLC (UV) and qualitative LC–MS/MS analysis. The LC–MS analysis allowing the additional detection of 17,18-bis-nor-antidesmone, 18-nor-antidesmone, 8-dihydroantidesmone and 8-deoxoantidesmone was carried out in the selected reaction monitoring (SRM) mode. Leaf material from herbarium specimens of 13 Antidesma spp., Hyeronima alchorneoides and Thecacoris stenopetala (all subtribe Antidesminae), as well as Maesobotrya barteri, Aporosa octandra (both Scepinae) and Uapaca robynsii (Uapacinae) were analysed. Additionally, freshly collected samples of different plant parts of two Antidesma spp. were investigated to ensure the significance of the results on herbarium specimens and to compare the antidesmone content in bark, root and leaves. Antidesmone could be unambiguously identified in 12 of 13 Antidesma spp., as well as in the two other investigated genera of subtribe Antidesminae, in levels of up to 65 mg/kg plant dry weight. Antidesmone was not found in specimens from other subtribes. Antidesmone-derived compounds occur in much lower concentrations than antidesmone.Selected species of the tribe Antidesmeae (Euphorbiaceae, subfamily Phyllanthoideae) have been screened for the occurrence of antidesmone and some derived compounds by HPLC and LC–MS/MS analysis, including selected reaction monitoring (SRM). Antidesmone could be identified in 12 of 13 Antidesma species as well as in the two other investigated genera of subtribe Antidesminae. It was not found in specimens from other subtribes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2143
TI  - Struktur- Wirkungsbeziehungen von Opioiden: Agonist oder Antagonist?
JO  - Pharmazie in unserer Zeit
PY  - 2002
SP  - 60-68
AU  - Brandt, W.
AU  - 
VL  - 31
UR  - 
DO  - 10.1002/1615-1003(200201)31:1&lt;60::AID-PAUZ60&gt;3.0.CO;2-L
AB  - Die Charakterisierung der pharmakophoren Strukturmerkmale der Opioide, die für deren Affinität und Spezifität zu ihren Rezeptoren verantwortlich sind, steht nach wie vor im Mittelpunkt vieler Untersuchungen mittels experimenteller und theoretischer Methoden. In der Vergangenheit konnten molekulare Modelle entwickelt werden, die zur Charakterisierung der wichtigsten pharmakophoren Elemente von μ‐, δ, ‐und κ‐ selektiven Opioiden führten. Diese Modelle können die Grundlage zur Entwicklung weiterer spezifischer Opioide mit reduzierten Nebenwirkungen darstellen. Die Kenntnis der Raumstruktur des Rinder‐Rhodopsin, eines zu den Opioidrezeptoren homologen G‐Protein‐gekoppelten Rezeptors, ermöglicht jetzt die Modellierung der Strukturen der Opioidrezeptoren. Durch eine detaillierte Analyse der potenziellen Bindungsstellen der Opioide an ihre Rezeptoren können neue Einblicke in die Zusammenhänge zwischen den chemischen Strukturen der Opioide und ihren Wirkungen gewonnen werden.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2142
TI  - Predicted Alterations in Tertiary Structure of the N-Terminus of Na+/K+-ATPase α-Subunit Caused by Phosphorylation or Acidic Replacement of the PKC Phosphorylation Site Ser-23
JO  - Cell Biochem. Biophys.
PY  - 2002
SP  - 83-96
AU  - Brandt, W.
AU  - Anders, A.
AU  - Vasilets, L. A.
AU  - 
VL  - 37
UR  - 
DO  - 10.1385/CBB:37:2:083
AB  - The protein kinase C (PKC)-mediated phosphorylation of the Na+/K+-ATPase α-subunit has been shown to play an important role in regulation of the Na+/K+-ATPase activity. In the rat α1-subunit, phosphorylation occurs at Ser-23 and results in inhibition of the transport function of the Na+/K+-ATPase, which is mimicked by replacing the Ser-23 by the negatively charged glutamic acid or by aspartic acid. Using comparative molecular modeling, we investigated whether phosphorylation or acidic replacement at position 23 causes a dramatic change in the molecular electrostatic potential at position 23 as a result of insertion of a negative charge of the phosphoryl group or Glu per se, or whether, alternatively, the modification causes larger-scale conformational changes in the N-terminus of the α-subunit. The results predict a considerable conformational change of the 30-residue stretch around Ser-23 when mutated to the residues carrying a net negative charge or being phosphorylated. The structural rearrangements occur within the N-terminal helix-loop-helix motif with a set of charged residues. This motif has structural homology with one in the Ca2+-ATPase and may form a function-related structural site in the P-type ATPases. Comparative molecular modeling indicates a lengthening of the interhelical loop and an order-to-disorder transition by disrupting a helix at position 23 because of posphorylation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 154
TI  - Development and Validation of Homology Models of Human Cathepsins K, S, H, and F
T2  - Cellular Peptidases in Immune Functions and Diseases 2
PB  - Adv. Exp. Med. Biol.
PY  - 2002
SP  - 255-260
AU  - Fengler, A.
AU  - Brandt, W.
AU  - 
VL  - 477
UR  - 
SN  - 978-0-306-46826-1
DO  - 10.1007/0-306-46826-3_27
AB  - Models of the tertiary structures of cathepsins K, S, H, and F were constructed by using homology protein modelling methods and refinements by interactive graphics and energy minimisation. The predicted structures yield information regarding their substrate binding sites and indicate the residues surrounding these sites. The ligandbinding sites were characterised and compared with each other by means of calculated molecular electrostatic surface potentials. This will allow designing and development of new ligands specific for these cathepsins in future investigations.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 153
TI  - Down regulation of T-cell activation by synthetic dipeptidyl peptidase IV inhibitors with the N.terminal MXP sequence
T2  - PEPTIDES 2002
PB  - 
PY  - 2002
SP  - 750-751
AU  - Faust, J.
AU  - Wrenger, S.
AU  - Reinhold, D.
AU  - Kähne, T.
AU  - Lorey, S.
AU  - Stöckel-Maschek, A.
AU  - Brandt, W.
AU  - Mrestani-Klaus, C.
AU  - Stiebitz, B.
AU  - Fuchs, P.
AU  - Ansorge, S.
AU  - Neubert, K.
AU  - 
VL  - 
UR  - 
AB  - 
A2  - Bendetti, E. &amp; Predone, C., eds.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 151
TI  - Review: Novel Cysteine Proteases of the Papain Family
T2  - Cellular Peptidases in Immune Functions and Diseases 2
PB  - Adv. Exp. Med. Biol.
PY  - 2002
SP  - 241-254
AU  - Bühling, F.
AU  - Fengler, A.
AU  - Brandt, W.
AU  - Welte, T.
AU  - Ansorge, S.
AU  - Nagler, D. K.
AU  - 
VL  - 477
UR  - 
SN  - 978-0-306-46826-1
DO  - 10.1007/0-306-46826-3_26
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 150
TI  - Development of a Tertiary-Structure Model of the C-Terminal Domain of DPP IV
T2  - Cellular Peptidases in Immune Functions and Diseases 2
PB  - Adv. Exp. Med. Biol.
PY  - 2002
SP  - 97-101
AU  - Brandt, W.
AU  - 
VL  - 477
UR  - 
SN  - 978-0-306-46826-1
DO  - 10.1007/0-306-46826-3_9
AB  - Based on the recently published structure of prolyl oligopeptidase (POP) a model of the C-terminal part of dipeptidyl peptidase IV (DPP IV) which contains the active site has been developed. The structure of the model of DPP IV shows considerable similarity to the structure of POP particularly in the active site. A hydrophobic pocket (Tyr666, Tyr670, Tyr 631, Val556) forms the S1-binding site for recognition of proline. Tyr547 may stabilise the oxyanion formed in the tetrahedral intermediates by a strong hydrogen bond. The positively charged N-terminus of ligands of DPP IV is recognised by forming a salt bridge with the acidic side chain Glu668. A second hydrophobic pocket (S2′ to S5′) may represent an important binding site for HIV-1 Tat-protein derivatives, chemokines and others.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 160
TI  - Effects of Nonapeptides Derived From the N-terminal Structure of Human Immunodeficiency Virus-1 (HIV-1) Tat on Suppression of CD26-Dependent T Cell Growth
T2  - Cellular Peptidases in Immune Functions and Diseases 2
PB  - Adv. Exp. Med. Biol.
PY  - 2002
SP  - 161-165
AU  - Wrenger, S.
AU  - Reinhold, D.
AU  - Faust, J.
AU  - Mrestani-Klaus, C.
AU  - Brandt, W.
AU  - Fengler, A.
AU  - Neubert, K.
AU  - Ansorge, S.
AU  - 
VL  - 477
UR  - 
SN  - 978-0-306-46826-1
DO  - 10.1007/0-306-46826-3_18
AB  - The human immunodeficiency virus-1 (HIV-1) transactivator Tat occurs extracellularly and exerts immunosuppressive effects. Interestingly, Tat inhibits dipeptidyl peptidase IV (DP IV) activity of the T cellactivation marker CD26. The short N-terminal nonapeptideTat(l-9), MDPVDPNIE, also inhibits DP IV activity and suppresses DNA synthesis of tetanus toxoid-stimulated peripheral blood mononuclear cells (PBMC). Here, we present the influence of amino acid exchanges in the first three positions of Tat(l-9). For instance, the replacement of D2 of Tat(l-9) by G or K generated peptides, which inhibit DP IV-catalyzed IL-2(1-12) cleavage nearly threefold stronger. Similar effects were observed on the suppression of DNA synthesis of Tetanus toxoid-stimulated PBMC. This correlation suggests that Tat(l-9)-deduced peptides mediate antiproliferative effects at least in part via specific DP IV interactions and supports the hypothesis that CD26 plays a key role in the regulation of lymphocyte growth.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2211
TI  - Determination of preferred conformations of brassinosteroids by means of NMR investigations and Boltzmann statistical analysis of simulated annealing calculations
JO  - J. Mol. Model.
PY  - 2001
SP  - 34-42
AU  - Drosihn, S.
AU  - Porzel, A.
AU  - Brandt, W.
AU  - 
VL  - 7
UR  - 
DO  - 10.1007/s008940100009
AB  - Brassinosteroids are a class of steroidal phytohormones with high growth-promoting properties. The preferred side-chain conformations of 10 brassinosteroids were determined by means of detailed NMR investigations and molecular-modeling studies. Vacuum conformations obtained by simulated annealing calculations and Boltzmann statistical analysis were compared with solution conformations derived from NOE experiments and molecular dynamic simulations, and with X-ray structures. In general, results from simulated annealing calculations and NMR-supported molecular dynamics simulations are in good agreement. For some of the compounds investigated the conformation was less well-defined at the end of the side-chain. It could be shown that the energetically most favorable and most probable conformations also include the conformations obtained by NMR supported molecular-dynamics calculations and by X-ray analysis. For the most bioactive compound brassinolide (1) the majority of conformations show a side-chain bent towards the β-face of the steroid skeleton, whereas for the less bioactive brassinosteroids, conformations with straight side-chains or side-chains bent towards the α-face are more frequent.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2205
TI  - Alkaloidal, Megastigmane and Lignan Glucosides from Antidesma membranaceum (Euphorbiaceae)
JO  - Eur. J. Org. Chem.
PY  - 2001
SP  - 3537-3543
AU  - Buske, A.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Adam, G.
AU  - 
VL  - 2001
UR  - 
DO  - 10.1002/1099-0690(200109)2001:18&lt;3537::AID-EJOC3537&gt;3.0.CO;2-A
AB  - Two novel alkaloidal glucosides derived from the recently discovered antidesmone (1 ), together with four known megastigmane and three lignan glucosides, two of which had not previously been described, were isolated from 1‐butanol extracts of Antidesma membranaceum  (Euphorbiaceae). The structural elucidation of (17RS )‐17‐(β‐D ‐glucopyranosyloxy)antidesmone (2 ) and (17RS )‐8‐deoxo‐17‐(β‐D ‐glucopyranosyloxy)antidesmone (3 ) is based on 1H, 13C, COSY, NOESY, HMQC and HMBC NMR spectra, together with LC/ESI‐CIDMS and CD data. Determination of the absolute configuration at C‐17 was accomplished by comparison with 1H NMR spectroscopic data for alk‐2‐yl β‐D ‐glucopyranosides, an approach that also proved useful for the megastigmane glucosides blumenyl C β‐D ‐glucopyranoside (4 ), 3‐oxo‐α‐ionyl β‐D ‐glucopyranoside (5 ), blumenyl B β‐D ‐glucopyranoside (6 ) and blumenyl A β‐D ‐glucopyranoside (7 ). The lignan glucosides lyoniresin‐4‐yl β‐D ‐glucopyranoside (8 ), 4′‐O‐methyllyoniresin‐4‐yl β‐D ‐glucopyranoside (9 ) and secoisolariciresin‐4‐yl β‐D ‐glucopyranoside (10 ), featuring an unusual glucosylation position, were investigated with the aid of 1H and 2D NMR, CD and MS data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2204
TI  - New C2-symmetric chiral disulfide ligands derived from (R)-cysteine
JO  - Tetrahedron
PY  - 2001
SP  - 3291-3295
AU  - Braga, A. L.
AU  - Appelt, H. R.
AU  - Schneider, P. H.
AU  - Rodrigues, O. E. D.
AU  - Silveira, C. C.
AU  - Wessjohann, L. A.
AU  - 
VL  - 57
UR  - 
DO  - 10.1016/S0040-4020(01)00199-5
AB  - Several sulfur-containing optically active C2-symmetrical ligands have been synthesized from (R)-cysteine and applied successfully as chiral catalysts in the asymmetric addition of diethylzinc to aldehydes. The resulting secondary alcohols could be obtained in good yields and excellent enantiomeric excess.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2203
TI  - Constituents of Aloe rubroviolacea
JO  - Fitoterapia
PY  - 2001
SP  - 78-79
AU  - Blitzke, T.
AU  - Masaoud, M.
AU  - Schmidt, J.
AU  - 
VL  - 72
UR  - 
DO  - 10.1016/S0367-326X(00)00239-2
AB  - The isolation of three C-glycosyl chromones, four anthraquinones and a mixture of phytosterols from the leaves of Aloe rubroviolacea was reported.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2202
TI  - 7-O-Methylaloeresin A - A New Chromone Glycoside from Commiphora socotrana
JO  - Nat. Prod. Lett.
PY  - 2001
SP  - 27-33
AU  - Blitzke, T.
AU  - Schmidt, J.
AU  - Masaoud, M.
AU  - 
VL  - 15
UR  - 
DO  - 10.1080/10575630108041254
AB  - A new 5-methylchromone glycoside, named 7-O-methylaloeresin A (2-acetonyl-8-C-β-D[2′-O-(E)-4-hydroxycinnamoyl]glucopyranosyl-7-methoxy-5-methylchromone, 1), was isolated from Commiphora socotrana (Burseraceae). Its structure was elucidated by spectroscopic data (MS, UV, 1H- and 13C-NMR).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2201
TI  - Enzymatic and non-enzymatic lipid peroxidation in leaf development
JO  - BBA-Mol. Cell Biol. Lipids
PY  - 2001
SP  - 266-276
AU  - BERGER, S.
AU  - Weichert, H.
AU  - Porzel, A.
AU  - Wasternack, C.
AU  - Kühn, H.
AU  - Feussner, I.
AU  - 
VL  - 1533
UR  - 
DO  - 10.1016/S1388-1981(01)00161-5
AB  - Enzymatic and non-enzymatic lipid peroxidation has been implicated in programmed cell death, which is a major process of leaf senescence. To test this hypothesis we developed a high-performance liquid chromatography (HPLC) method for a simultaneous analysis of the major hydro(pero)xy polyenoic fatty acids. Quantities of lipid peroxidation products in leaves of different stages of development including natural senescence indicated a strong increase in the level of oxygenated polyenoic fatty acids (PUFAs) during the late stages of leaf senescence. Comprehensive structural elucidation of the oxygenation products by means of HPLC, gas chromatography/mass spectrometry and 1H nuclear magnetic resonance suggested a non-enzymatic origin. However, in some cases a small share of specifically oxidized PUFAs was identified suggesting involvement of lipid peroxidizing enzymes. To inspect the possible role of enzymatic lipid peroxidation in leaf senescence, we analyzed the abundance of lipoxygenases (LOXs) in rosette leaves of Arabidopsis. LOXs and their product (9Z,11E,13S,15Z)-13-hydroperoxy-9,11,15-octadecatrienoic acid were exclusively detected in young green leaves. In contrast, in senescing leaves the specific LOX products were overlaid by large amounts of stereo-random lipid peroxidation products originating from non-enzymatic oxidation. These data indicate a limited contribution of LOXs to total lipid peroxidation, and a dominant role of non-enzymatic lipid peroxidation in late stages of leaf development.
A2  - 
C1  - Bioorganic Chemistry; Molecular Signal Processing
ER  - 


TY  - JOUR
ID  - 2200
TI  - Patterns of phenylpropanoids in non-inoculated and potato virus Y-inoculated leaves of transgenic tobacco plants expressing yeast-derived invertase
JO  - Phytochemistry
PY  - 2001
SP  - 535-541
AU  - Baumert, A.
AU  - Mock, H.-P.
AU  - Schmidt, J.
AU  - Herbers, K.
AU  - Sonnewald, U.
AU  - Strack, D.
AU  - 
VL  - 56
UR  - 
DO  - 10.1016/S0031-9422(00)00422-2
AB  - The patterns of secondary metabolites in leaves of yeast invertase-transgenic tobacco plants (Nicotiana tabacum L. cv. Samsun NN) were analyzed. Plants expressing cytosolic yeast-derived invertase (cytInv) or apoplastic (cell wall associated) yeast invertase (cwInv) showed a characteristic phytochemical phenotype compared to untransformed controls (wild-type plants). The level of phenylpropanoids decreased in the cytInv plants but increased in the cwInv plants, which showed an induced de novo synthesis of a caffeic acid amide, i.e. N-caffeoylputrescine. In addition, the level of the coumarin glucoside scopolin was markedly enhanced. Increased accumulation of scopolin in the cwInv plants is possibly correlated with the induction of defense reactions and the appearance of necrotic lesions similar to the hypersensitive response caused by avirulent pathogens. This is consistent with results from potato virus Y-infected plants. Whereas there was no additional increase in the coumarins in leaves following infection in cwInv plants, wild-type plants showed a slight increase and cytInc a marked increase.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2198
TI  - Flavonoids and other phenolics from leaves of two Marlierea species (Myrtaceae)
JO  - Biochem. Syst. Ecol.
PY  - 2001
SP  - 653-654
AU  - Amaral, A. C. F.
AU  - Kuster, R. M.
AU  - de Santana Bessa, W.
AU  - Barnes, R. A.
AU  - Kaplan, M. A. C.
AU  - Wessjohann, L. A.
AU  - 
VL  - 29
UR  - 
DO  - 10.1016/S0305-1978(00)00089-2
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2234
TI  - R,R-(+)-Bis[(3-benzyloxazolan-4-yl)methyl] disulfide
JO  - Acta Cryst. E
PY  - 2001
SP  - o41-o42
AU  - Schulz Lang, E.
AU  - Burrow, R. A.
AU  - Braga, A. L.
AU  - Appelt, H. R.
AU  - Schneider, P. H.
AU  - Silveira, C. C.
AU  - Wessjohann, L. A.
AU  - 
VL  - 57
UR  - 
DO  - 10.1107/S160053680001878X
AB  - R,R-Bis­[(3-benzyl­oxazolan-4-yl)-methyl] di­sulfide, C22H28N2O2S2, is a chiral di­sulfide which is a highly effective catalyst for the enantioselective addition of diethyl­zinc to aldehydes, including aliphatic ones. The mol­ecule has crystallographic twofold rotation symmetry.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2233
TI  - Structural Investigations of 5-Methylchromone Glycosides from Aloe Species by Liquid Chromatography/Electrospray Tandem Mass Spectrometry
JO  - Eur. J. Mass Spectrom.
PY  - 2001
SP  - 481-490
AU  - Schmidt, J.
AU  - Blitzke, T.
AU  - Masaoud, M.
AU  - 
VL  - 7
UR  - 
DO  - 10.1255/ejms.464
AB  - The mass spectral behavior of a series of 5-methylchromone glycosides isolated from two Aloe species was investigated by liquid chromatography/positive-ion electrospray (ES) mass spectrometry using collision-induced dissociation (CID) mass spectrometry. The CID mass spectra of the [M + H]+ ions show a typical fragmentation pattern reflecting the several substructures (substitution at C-7, C-9 and C-10, position and nature of the ester moiety at C-2) of the 5-methylchromone glycosides. Besides a series of known 5-methylchromone glycosides, nine new compounds of this type were identified by LC/ES-CIDMS from Aloe rubroviolacea and Aloe perryi (Aloeaceae).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2232
TI  - Betalains of Celosia argentea
JO  - Phytochemistry
PY  - 2001
SP  - 159-165
AU  - Schliemann, W.
AU  - Cai, Y.
AU  - Degenkolb, T.
AU  - Schmidt, J.
AU  - Corke, H.
AU  - 
VL  - 58
UR  - 
DO  - 10.1016/S0031-9422(01)00141-8
AB  - The betalains of yellow, orange and red inflorescences of common cockscomb (Celosia argentea var. cristata) were compared and proved to be qualitatively identical to those of feathered amaranth (Celosia argentea var. plumosa). In addition to the known compounds amaranthin and betalamic acid, the structures of three yellow pigments were elucidated to be immonium conjugates of betalamic acid with dopamine, 3-methoxytyramine and (S)-tryptophan by various spectroscopic techniques and comparison to synthesized reference compounds; the latter two are new to plants. Among the betacyanins occurring in yellow inflorescences in trace amounts, the presence of 2-descarboxy-betanidin, a dopamine-derived betacyanin, has been ascertained. The detection of high dopamine concentration may be of toxicological relevance in use of yellow inflorescences as a vegetable and in traditional Chinese medicine, common uses for the red inflorescences of common cockscomb.The betaxanthins of two Celosia argentea varieties were identified as betalamic acid conjugates of dopamine (1), 3-methoxytyramine (2) and (S)-tryptophan.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2223
TI  - Formation and occurrence of dopamine-derived betacyanins
JO  - Phytochemistry
PY  - 2001
SP  - 429-436
AU  - Kobayashi, N.
AU  - Schmidt, J.
AU  - Wray, V.
AU  - Schliemann, W.
AU  - 
VL  - 56
UR  - 
DO  - 10.1016/S0031-9422(00)00383-6
AB  - In light of the fact that the main betaxanthin (miraxanthin V) and the major betacyanin (2-descarboxy-betanidin) in hairy root cultures of yellow beet (Beta vulgaris L.) are both dopamine-derived, the occurrence of similar structures for the minor betacyanins was also suggested. By HPLC comparison with the betacyanins obtained by dopamine administration to beet seedlings, enzymatic hydrolysis, LCMS and 1H NMR analyses, the minor betacyanins from hairy roots were identified as 2-descarboxy-betanin and its 6′-O-malonyl derivative. A short-term dopamine administration experiment with fodder beet seedlings revealed that the condensation step between 2-descarboxy-cyclo-Dopa and betalamic acid is the decisive reaction, followed by glucosylation and acylation. From these data a pathway for the biosynthesis of dopamine-derived betalains is proposed. Furthermore, the occurrence of these compounds in various cell and hairy root cultures as well as beet plants (Fodder and Garden Beet Group) is shown.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2215
TI  - Furanocoumarins from Dorstenia gigas
JO  - Phytochemistry
PY  - 2001
SP  - 611-621
AU  - Franke, K.
AU  - Porzel, A.
AU  - Masaoud, M.
AU  - Adam, G.
AU  - Schmidt, J.
AU  - 
VL  - 56
UR  - 
DO  - 10.1016/S0031-9422(00)00419-2
AB  - A series of linear and angular prenylated furanocoumarins and a benzofuran derivative were isolated from leaves and twigs of Dorstenia gigas (Moraceae), a plant occurring endemically on Socotra Island (Yemen). The structures were elucidated by spectroscopic methods (NMR, MS, UV) and chemical derivatization.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2214
TI  - Cardanols from Leaves of Rhus thyrsiflora
JO  - Planta Med.
PY  - 2001
SP  - 477-479
AU  - Franke, K.
AU  - Masaoud, M.
AU  - Schmidt, J.
AU  - 
VL  - 67
UR  - 
DO  - 10.1055/s-2001-15813
AB  - A mixture of 3-substituted alkyl- and alkenylphenols including nine new compounds (cardanols) was isolated from leaves of the Yemenian plant Rhus thyrsiflora (Anacardiaceae) and identified by GC-MS. The position of the double bond in the compounds bearing a monolefinic side chain was determined by their typical MS fragmentation patterns after hydroxylation and trimethylsilylation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2240
TI  - Study of the Role of Antimicrobial Glucosinolate-Derived Isothiocyanates in Resistance of Arabidopsis to Microbial Pathogens
JO  - Plant Physiol.
PY  - 2001
SP  - 1688-1699
AU  - Tierens, K. F. M.-J.
AU  - THOMMA, B. P. H. J.
AU  - Brouwer, M.
AU  - Schmidt, J.
AU  - Kistner, K.
AU  - Porzel, A.
AU  - Mauch-Mani, B.
AU  - Cammue, B. P. A.
AU  - Broekaert, W. F.
AU  - 
VL  - 125
UR  - 
DO  - 10.1104/pp.125.4.1688
AB  - Crude aqueous extracts from Arabidopsis leaves were subjected to chromatographic separations, after which the different fractions were monitored for antimicrobial activity using the fungus Neurospora crassa as a test organism. Two major fractions were obtained that appeared to have the same abundance in leaves from untreated plants versus leaves from plants challenge inoculated with the fungusAlternaria brassicicola. One of both major antimicrobial fractions was purified to homogeneity and identified by 1H nuclear magnetic resonance, gas chromatography/electron impact mass spectrometry, and gas chromatography/chemical ionization mass spectrometry as 4-methylsulphinylbutyl isothiocyanate (ITC). This compound has previously been described as a product of myrosinase-mediated breakdown of glucoraphanin, the predominant glucosinolate in Arabidopsis leaves. 4-Methylsulphinylbutyl ITC was found to be inhibitory to a wide range of fungi and bacteria, producing 50% growth inhibition in vitro at concentrations of 28 μm for the most sensitive organism tested (Pseudomonas syringae). A previously identified glucosinolate biosynthesis mutant, gsm1-1, was found to be largely deficient in either of the two major antimicrobial compounds, including 4-methylsulphinylbutyl ITC. The resistance ofgsm1-1 was compared with that of wild-type plants after challenge with the fungi A. brassicicola,Plectosphaerella cucumerina, Botrytis cinerea, Fusarium oxysporum, orPeronospora parasitica, or the bacteria Erwinia carotovora or P. syringae. Of the tested pathogens, only F. oxysporum was found to be significantly more aggressive on gsm1-1 than on wild-type plants. Taken together, our data suggest that glucosinolate-derived antimicrobial ITCs can play a role in the protection of Arabidopsis against particular pathogens.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2291
TI  - Down-regulation of T Cell Activation following Inhibition of Dipeptidyl Peptidase IV/CD26 by the N-terminal Part of the Thromboxane A2 Receptor
JO  - J. Biol. Chem.
PY  - 2000
SP  - 22180-22186
AU  - Wrenger, S.
AU  - Faust, J.
AU  - Mrestani-Klaus, C.
AU  - Fengler, A.
AU  - Stöckel-Maschek, A.
AU  - Lorey, S.
AU  - Kähne, T.
AU  - Brandt, W.
AU  - Neubert, K.
AU  - Ansorge, S.
AU  - Reinhold, D.
AU  - 
VL  - 275
UR  - 
DO  - 10.1074/jbc.M002338200
AB  - Using synthetic inhibitors, it has been shown that the ectopeptidase dipeptidyl peptidase IV (DP IV) (CD26) plays an important role in the activation and proliferation of T lymphocytes. The human immunodeficiency virus-1 Tat protein, as well as the N-terminal nonapeptide Tat(1–9) and other peptides containing the N-terminal sequence XXP, also inhibit DP IV and therefore T cell activation. Studying the effect of amino acid exchanges in the N-terminal three positions of the Tat(1–9) sequence, we found that tryptophan in position 2 strongly improves DP IV inhibition. NMR spectroscopy and molecular modeling show that the effect of Trp2-Tat(1–9) could not be explained by significant alterations in the backbone structure and suggest that tryptophan enters favorable interactions with DP IV. Data base searches revealed the thromboxane A2 receptor (TXA2-R) as a membrane protein extracellularly exposing N-terminal MWP. TXA2-R is expressed within the immune system on antigen-presenting cells, namely monocytes. The N-terminal nonapeptide of TXA2-R, TXA2-R(1–9), inhibits DP IV and DNA synthesis and IL-2 production of tetanus toxoid-stimulated peripheral blood mononuclear cells. Moreover, TXA2-R(1–9) induces the production of the immunosuppressive cytokine transforming growth factor-β1. These data suggest that the N-terminal part of TXA2-R is an endogenous inhibitory ligand of DP IV and may modulate T cell activation via DP IV/CD26 inhibition.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2290
TI  - Synthesis of natural-product-based compound libraries
JO  - Curr. Opin. Chem. Biol.
PY  - 2000
SP  - 303-309
AU  - Wessjohann, L. A.
AU  - 
VL  - 4
UR  - 
DO  - 10.1016/S1367-5931(00)00093-4
AB  - Natural products cover a diversity space not yet available from synthetic libraries, with an unrivalled success rate as drug leads. The combinatorial synthesis of non-oligomeric natural-product-based libraries, however, is still limited to few examples because access to easily modified units strongly depends on the availability of a core structure either from a natural source, or through a suitable synthetic route. Only a few resourceful groups have managed the latter approach for more demanding multifunctional natural drug leads, such as epothilones.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2283
TI  - FACKEL is a sterol C-14 reductase required for organized cell division and expansion in Arabidopsis embryogenesis
JO  - Genes Dev.
PY  - 2000
SP  - 1471-1484
AU  - Schrick, K.
AU  - Mayer, U.
AU  - Horrichs, A.
AU  - Kuhnt, C.
AU  - Bellini, C.
AU  - Dangl, J.
AU  - Schmidt, J.
AU  - Jürgens, G.
AU  - 
VL  - 14
UR  - http://genesdev.cshlp.org/content/14/12/1471
DO  - 10.1101/gad.14.12.1471
AB  - In flowering plants, the developing embryo consists of growing populations of cells whose fates are determined in a position-dependent manner to form the adult organism. Mutations in the FACKEL(FK) gene affect body organization of theArabidopsis seedling. We report that FK is required for cell division and expansion and is involved in proper organization of the embryo. We isolated FK by positional cloning. Expression analysis in embryos revealed that FK mRNA becomes localized to meristematic zones. FK encodes a predicted integral membrane protein related to the vertebrate lamin B receptor and sterol reductases across species, including yeast sterol C-14 reductase ERG24. We provide functional evidence that FK encodes a sterol C-14 reductase by complementation of erg24. GC/MS analysis confirmed that fk mutations lead to accumulation of intermediates in the biosynthetic pathway preceding the C-14 reductase step. Although fk represents a sterol biosynthetic mutant, the phenotype was not rescued by feeding with brassinosteroids (BRs), the only plant sterol signaling molecules known so far. We propose that synthesis of sterol signals in addition to BRs is important in mediating regulated cell growth and organization during embryonic development. Our results indicate a novel role for sterols in the embryogenesis of plants.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2282
TI  - Identification of metabolically formed glucosyl conjugates of [17-D2]-GA34
JO  - Phytochem. Anal.
PY  - 2000
SP  - 232-235
AU  - Schneider, G.
AU  - Koch, M.
AU  - Fuchs, P.
AU  - Schmidt, J.
AU  - 
VL  - 11
UR  - 
DO  - 10.1002/1099-1565(200007/08)11:4&lt;232::AID-PCA525&gt;3.0.CO;2-F
AB  - After application of [17‐D2]‐GA34 to seedlings of Phaseolus coccineus  L. cv. Prizewinner, both metabolically formed conjugates [17‐D2]‐GA34‐2‐O‐glucoside and [17‐D2]‐GA34‐glucosyl ester could be established structurally. The identification was based on data from GC‐MS as well as LC‐ESI‐tandem MS (negative ions) techniques (daughter ion scan, parent ion scan, selected ion monitoring, selected reaction monitoring), and NMR studies.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2281
TI  - Metabolic Transformation of the Brassinosteroid 24-Epi-castasterone by the Cockroach Periplaneta americana
JO  - Z. Naturforsch. C
PY  - 2000
SP  - 233-239
AU  - Schmidt, J.
AU  - Richter, K.
AU  - Voigt, B.
AU  - Adam, G.
AU  - 
VL  - 55
UR  - 
DO  - 10.1515/znc-2000-3-415
AB  - After feeding of 24-epi-castasterone to the cockroach Periplaneta americana an organspecific epimerization of the brassinosteroid to 2,24-depi-castasterone could be detected in female insects. The metabolite being observed only in the ovaries and not in the testes of the insect was identified by GC/MS in comparison with a synthesized authentic sample. Contrary, 24-epi-brassinolide is not metabolized in the sexual organs of Periplaneta americana. This is the first evidence of a metabolic transformation of a brassinosteroid in insects.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2277
TI  - Fissistigmatins A–D: Novel Type Natural Products with Flavonoid–Sesquiterpene Hybrid Structure from Fissistigma bracteolatum
JO  - Tetrahedron
PY  - 2000
SP  - 865-872
AU  - Porzel, A.
AU  - Phuong Lien, T.
AU  - Schmidt, J.
AU  - Drosihn, S.
AU  - Wagner, C.
AU  - Merzweiler, K.
AU  - Van Sung, T.
AU  - Adam, G.
AU  - 
VL  - 56
UR  - 
DO  - 10.1016/S0040-4020(99)01049-2
AB  - From Fissistigma bracteolatum Chatt. (Annonaceae), a Vietnamese folk medicinal plant, the novel type natural products fissistigmatin A–D (1–4), being composed of a flavonoid and a sesquiterpene moiety, were isolated. Their structures were elucidated by extensive NMR techniques, MS, CD, molecular modelling calculations and X-ray analysis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2269
TI  - Secondary products in mycorrhizal roots of tobacco and tomato
JO  - Phytochemistry
PY  - 2000
SP  - 473-479
AU  - Maier, W.
AU  - Schmidt, J.
AU  - Nimtz, M.
AU  - Wray, V.
AU  - Strack, D.
AU  - 
VL  - 54
UR  - 
DO  - 10.1016/S0031-9422(00)00047-9
AB  - Colonization of the roots of various tobacco species and cultivars (Nicotiana glauca Grah., N. longiflora Cav., N. rustica L., N. tabacum L., N. tabacum L. cv. Samsun NN, N. sanderae hort. Sander ex Wats.) as well as tomato plants (Lycopersicon esculentum L. cv. Moneymaker) by the arbuscular mycorrhizal fungus Glomus intraradices Schenck and Smith resulted in the accumulation of several glycosylated C13 cyclohexenone derivatives. Eight derivatives were isolated from the mycorrhizal roots by preparative high performance liquid chromatography (HPLC) and spectroscopically identified (MS and NMR) as mono-, di- and triglucosides of 6-(9-hydroxybutyl)-1,1,5-trimethyl-4-cyclohexen-3-one and monoglucosides of 6-(9-hydroxybutyl)-1,5-dimethyl-4-cyclohexen-3-one-1-carboxylic acid and 6-(9-hydroxybutyl)-1,1-dimethyl-4-cyclohexen-3-one-5-carboxylic acid. In contrast to the induced cyclohexenone derivatives, accumulation of the coumarins scopoletin and its glucoside (scopolin) in roots of N. glauca Grah. and N. tabacum L. cv. Samsun NN, was markedly suppressed.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2268
TI  - Chalconoids from Fissistigma bracteolatum
JO  - Phytochemistry
PY  - 2000
SP  - 991-995
AU  - Lien, T. P.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Van Sung, T.
AU  - Adam, G.
AU  - 
VL  - 53
UR  - 
DO  - 10.1016/S0031-9422(99)00570-1
AB  - Phytochemical studies on the leaves of Fissistigma bracteolatum yielded besides the two known compounds 2-hydroxy-3,4,6-trimethoxychalcone (1) and 5,7,8-trimethoxyflav-3-ene (2), five new chalconoids 2-hydroxy-3,4,6-trimethoxychalcene (3), 2-hydroxy-3,4,6-trimethoxydihydrochalcone (4), 2′-hydroxy-3′,4′,6′-trimethoxydihydrochalcone (5), 2′-hydroxy-3′,4′,6′-trimethoxy-β′-methoxychalcane (6) and 2′-hydroxy-3′,4′,6′-trimethoxy-β′-ethoxychalcane (7). The structures of these compounds were determined by mass and NMR spectroscopic methods.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2264
TI  - Betalains from Christmas cactus
JO  - Phytochemistry
PY  - 2000
SP  - 419-426
AU  - Kobayashi, N.
AU  - Schmidt, J.
AU  - Nimtz, M.
AU  - Wray, V.
AU  - Schliemann, W.
AU  - 
VL  - 54
UR  - 
DO  - 10.1016/S0031-9422(00)00129-1
AB  - The presence of 14 betalain pigments have been detected by their characteristic spectral properties in flower petals of Christmas cactus (Schlumbergera x buckleyi). Along with the known vulgaxanthin I, betalamic acid, betanin and phyllocactin (6′-O-malonylbetanin), the structure of a new phyllocactin-derived betacyanin was elucidated by various spectroscopic techniques and carbohydrate analyses as betanidin 5-O-(2′-O-β-D-apiofuranosyl-6′-O-malonyl)-β-D-glucopyranoside. Among the more complex betacyanins occurring in trace amounts, the presence of a new diacylated betacyanin {betanidin 5-O-[(5″-O-E-feruloyl)-2′-O-β-D-apiofuranosyl-6′-O-malonyl)]-β-D-glucopyranoside} has been ascertained. Furthermore, the accumulation of betalains during flower development and their pattern in different organs of the flower has been examined.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2263
TI  - Indole alkaloid biosynthesis in Catharanthus roseus: new enzyme activities and identification of cytochrome P450 CYP72A1 as secologanin synthase
JO  - Plant J.
PY  - 2000
SP  - 797-804
AU  - Irmler, S.
AU  - Schröder, G.
AU  - St-Pierre, B.
AU  - Crouch, N. P.
AU  - Hotze, M.
AU  - Schmidt, J.
AU  - Strack, D.
AU  - Matern, U.
AU  - Schröder, J.
AU  - 
VL  - 24
UR  - 
DO  - 10.1111/j.1365-313X.2000.00922.x
AB  - The molecular characterization of CYP72A1 from Catharanthus roseus  (Madagascar periwinkle) was described nearly a decade ago, but the enzyme function remained unknown. We now show by in situ  hybridization and immunohistochemistry that the expression in immature leaves is epidermis‐specific. It thus follows the pattern previously established for early enzymes in the pathway to indole alkaloids, suggesting that CYP72A1 may be involved in their biosynthesis. The early reactions in that pathway, i.e. from geraniol to strictosidine, contain several candidates for P450 activities. We investigated in this work two reactions, the conversion of 7‐deoxyloganin to loganin (deoxyloganin 7‐hydroxylase, DL7H) and the oxidative ring cleavage converting loganin into secologanin (secologanin synthase, SLS). The action of DL7H has not been demonstrated in vitro  previously, and SLS has only recently been identified as P450 activity in one other plant. We show for the first time that both enzyme activities are present in microsomes from C . roseus  cell cultures. We then tested whether CYP72A1 expressed in E. coli  as a translational fusion with the C . roseus  P450 reductase (P450Red) has one or both of these activities. The results show that CYP72A1 converts loganin into secologanin.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2258
TI  - Clustering 3D-structures of small amino acid chains for detecting dependences from their sequential context in proteins
JO  - Proc. IEEE International Symposium on Bio-Informatics and Biomedical Engineering
PY  - 2000
SP  - 43-49
AU  - Hinneburg, A.
AU  - Keim, D. A.
AU  - Brandt, W.
AU  - 
VL  - 
UR  - 
DO  - 10.1109/BIBE.2000.889588
AB  - In the past, a good number of rotamer libraries have been published, which allow a deeper understanding of the conformational behavior of amino acid residues in proteins. Since the number of available high-resolution X-ray protein structures has grown significantly over the last years, a more comprehensive analysis of the conformational behavior is possible today. In this paper, we present a method to compile a new class of rotamer libraries for detecting interesting relationships between residue conformations and their sequential context in proteins. The method is based on a new algorithm for clustering residue conformations. To demonstrate the effectiveness of our method, we apply our algorithm to a library consisting of all 8000 tripeptide fragments formed by the 20 native amino acids. The analysis shows some very interesting new results, namely that some specific tripeptide fragments show some unexpected conformation of residues instead of the highly preferred conformation. In the neighborhood of two asparagine residues, for example, threonine avoids the conformation which is most likely to occur otherwise. The new insights obtained by the analysis are important in understanding the formation and prediction of secondary structure elements and will consequently be crucial for improving the state-of-the-art of protein folding.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2254
TI  - 24-Epi-castasterone and phytosterols from seeds of Maytenus boaria (Celastraceae)
JO  - Rev. Latinoam. Quím.
PY  - 2000
SP  - 111-115
AU  - Franke, K.
AU  - Kuhnt, C.
AU  - Schmidt, J.
AU  - Muñoz, O.
AU  - 
VL  - 27
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2251
TI  - Revised Structure of Antidesmone, an Unusual Alkaloid from Tropical Antidesma Plants (Euphorbiaceae)
JO  - Tetrahedron
PY  - 2000
SP  - 3691-3695
AU  - Bringmann, G.
AU  - Schlauer, J.
AU  - Rischer, H.
AU  - Wohlfarth, M.
AU  - Mühlbacher, J.
AU  - Buske, A.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Adam, G.
AU  - 
VL  - 56
UR  - 
DO  - 10.1016/S0040-4020(00)00289-1
AB  - The structure of antidesmone, an alkaloid from Antidesma membranaceum Müll. Arg. and A. venosum E. Mey. (Euphorbiaceae), was revised to be (S)-4,8-dioxo-3-methoxy-2-methyl-5-n-octyl-1,4,5,6,7,8-hexahydroquinoline [(S)-2], not the isoquinoline derivative 1, as assumed previously. The revision was initiated by biosynthetic feeding experiments of one of our groups.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2248
TI  - Constituents of Eulophia petersii
JO  - Fitoterapia
PY  - 2000
SP  - 593-594
AU  - Blitzke, T.
AU  - Masaoud, M.
AU  - Schmidt, J.
AU  - 
VL  - 71
UR  - 
DO  - 10.1016/S0367-326X(00)00169-6
AB  - The isolation of five known phenanthrenes and a mixture phytosterols from roots of Eulophia petersii is reported.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2245
TI  - Metabolites of 2-Aminophenol from Fruit Bodies of Lepiota americana (Agaricales)
JO  - Z. Naturforsch. C
PY  - 2000
SP  - 481-484
AU  - Aulinger, K.
AU  - Arnold, N.
AU  - Steglich, W.
AU  - 
VL  - 55
UR  - 
DO  - 10.1515/znc-2000-5-628
AB  - From the acetone extract of the North American toadstool Lepiota americana 2-aminophenoxazin-3-one (1) and a novel amino-1,4-benzoquinone derivative, lepiotaquinone (2), were isolated. The structure of 2 was confirmed by its preparation from 2-aminophenol and amino-1,4-benzoquinone.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2247
TI  - A chlorinated amide and piperidine alkaloids from Aloe sabaea
JO  - Phytochemistry
PY  - 2000
SP  - 979-982
AU  - Blitzke, T.
AU  - Porzel, A.
AU  - Masaoud, M.
AU  - Schmidt, J.
AU  - 
VL  - 55
UR  - 
DO  - 10.1016/S0031-9422(00)00269-7
AB  - Phytochemical investigations of Aloe sabaea afforded a new chlorinated amide, N-4′-chlorobutylbutyramide, and the toxic piperidine alkaloids coniine, γ-coniceine and the quarternary N,N-dimethylconiine. This is the first report of the occurrence of a chlorinated compound in the Aloeaceae family.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 167
TI  - Brassinosteroids - Structures, Analysis and Synthesis
T2  - Evolution of Metabolic Pathways
PB  - Recent Advances in Phytochemistry
PY  - 2000
SP  - 385-407
AU  - Schmidt, J.
AU  - Spengler, B.
AU  - Voigt, B.
AU  - Adam, G.
AU  - 
VL  - 34
UR  - 
DO  - 10.1016/S0079-9920(00)80013-1
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 165
TI  - N-Terminal HIV-1 Tat Nonapeptides as Inhibitors of Dipeptidyl Peptidase IV. Conformational Characterization
T2  - Cellular Peptidases in Immune Functions and Diseases 2
PB  - Adv. Exp. Med. Biol.
PY  - 2000
SP  - 125-129
AU  - Mrestani-Klaus, C.
AU  - Fengler, A.
AU  - Faust, J.
AU  - Brandt, W.
AU  - Wrenger, S.
AU  - Reinhold, D.
AU  - Ansorge, S.
AU  - Neubert, K.
AU  - 
VL  - 477
UR  - 
SN  - 978-0-306-46826-1
DO  - 10.1007/0-306-46826-3_13
AB  - Compared to the N-terminal nonapeptide of the HIV-1 Tat protein as inhibitor of activity of DP IV which is supposed to mediate the immunosuppressive effects of HIV-1 Tat, the Ile5 and Leu6 analogues showed strongly reduced inhibitory activity. Interestingly, replacement of Asp2 with Gly or Lys led to compounds with considerably enhanced inhibition. Therefore, we have applied 1H NMR spectroscopy and restrained molecular dynamics calculations to elucidate the molecular conformation of a series of Tat nonapeptides. Conformational backbone differences of these peptides as well as the nature and the arrangement of the side chains per se at significant positions preventing effective binding to DP IV might explain their different inhibitory activity on DP IV.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2318
TI  - Microbial conversion of jasmonates - hydroxylations by Aspergillus niger
JO  - Phytochemistry
PY  - 1999
SP  - 1147-1152
AU  - Miersch, O.
AU  - Porzel, A.
AU  - Wasternack, C.
AU  - 
VL  - 50
UR  - 
DO  - 10.1016/S0031-9422(98)00698-0
AB  - Aspergillus niger is able to hydroxylate the pentenyl side chain of (−)-jasmonic acid (JA) leading to (11S)- (−)-hydroxy-JA/ (11R)- (−)-hydroxy-JA (2:1) and (−)-11,12-didehydro-JA. Methyl (−)-jasmonate (JA-Me) is converted upon hydrolysis. During prolonged cultivation or at non-optimized isolation procedures, the 11-hydroxy- (9Z)-pentenyl side chain may isomerize to (10E)-9-hydroxy- and (9E)-11-hydroxy-compounds by allylic rearrangement. The fungus hydroxylates (±)-9,10-dihydro-JA at position C-11 into 11j-hydroxy-9,10-dihydro-JA. As JA-Me, the methyl dihydro-JA is hydroxylated only upon hydrolysis into the free acid.
A2  - 
C1  - Molecular Signal Processing; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2316
TI  - The arbuscular mycorrhizal fungus, Glomus intraradices , induces the accumulation of cyclohexenone derivatives in tobacco roots
JO  - Planta
PY  - 1999
SP  - 620-623
AU  - Maier, W.
AU  - Schmidt, J.
AU  - Wray, V.
AU  - Walter, M. H.
AU  - Strack, D.
AU  - 
VL  - 207
UR  - 
DO  - 10.1007/s004250050526
AB  - Tobacco (Nicotiana tabacum L.) plants were grown with and without the arbuscular mycorrhizal fungus, Glomus intraradices Schenk &amp; Smith. High-performance liquid chromatographic analyses of methanolic extracts from mycorrhizal and non-mycorrhizal tobacco roots revealed marked fungus-induced changes in the patterns of UV-detectable products. The UV spectra of these products, obtained from an HPLC photodiode array detector, indicated the presence of several blumenol derivatives. The most predominant compound among these derivatives was spectroscopically identified as 13-hydroxyblumenol C 9-O-gentiobioside (“nicoblumin”), i.e. the 9-O-(6′-O-β-glucopyranosyl)-β-glucopyranoside of 13-hydroxy-6-(3-hydroxybutyl)-1,1,5-trimethyl-4-cyclohexen-3-one, a new natural product. This is the first report on the identification of blumenol derivatives in mycorrhizal roots of a non-gramineous plant.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2315
TI  - Synthesis of a novel brassinosteroid type with an annelated dioxonane side chain
JO  - J. Chem. Soc., Perkin Trans. 1
PY  - 1999
SP  - 53-58
AU  - Lichtblau, D.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Voigt, B.
AU  - Adam, G.
AU  - 
VL  - 1999
UR  - 
DO  - 10.1039/A807078D
AB  - In studies directed towards the synthesis of 25-hydroxybrassinolide 1 we found, that upon reaction of intermediate 7 with trimethylaluminium–n-butyllithium an alkylating fission of the epoxide ring and rearrangement of the tetrahydropyranyl unit takes place to afford after deprotection the new dioxonane-annelated brassinosteroid 9.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2314
TI  - Phytochelatins and heavy metal tolerance
JO  - Phytochemistry
PY  - 1999
SP  - 1323-1328
AU  - Leopold, I.
AU  - Günther, D.
AU  - Schmidt, J.
AU  - Neumann, D.
AU  - 
VL  - 50
UR  - 
DO  - 10.1016/S0031-9422(98)00347-1
AB  - The induction and heavy metal binding properties of phytochelatins in heavy metal tolerant (Silene vulgaris) and sensitive (tomato) cell cultures, in water cultures of these plants and in Silene vulgaris grown on a medieval copper mining dump were investigated. Application of heavy metals to cell suspension cultures and whole plants of Silene vulgaris and tomato induces the formation of heavy metal–phytochelatin-complexes with Cu and Cd and the binding of Zn and Pb to lower molecular weight substances. The binding of heavy metal ions to phytochelatins seems to play only a transient role in the heavy metal detoxification, because the Cd- and Cu-complexes disappear in the roots of water cultures of Silene vulgaris between 7 and 14 days after heavy metal exposition. Free heavy metal ions were not detectable in the extracts of all investigated plants and cell cultures. Silene vulgaris plants grown under natural conditions on a mining dump synthesize low molecular weight heavy metal binding compounds only and show no complexation of heavy metal ions to phytochelatins. The induction of phytochelatins is a general answer of higher plants to heavy metal exposition, but only some of the heavy metal ions are able to form stable complexes with phytochelatins. The investigation of tolerant plants from the copper mining dump shows that phytochelatins are not responsible for the development of the heavy metal tolerant phenotypes.
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions
ER  - 


TY  - JOUR
ID  - 2312
TI  - Chromatographic resolution of peptide-like conjugates of jasmonic acid and of cucurbic acid isomers
JO  - J. Chromatogr. A
PY  - 1999
SP  - 103-107
AU  - Kramell, R.
AU  - Porzel, A.
AU  - Miersch, O.
AU  - Schneider, G.
AU  - Wasternack, C.
AU  - 
VL  - 847
UR  - 
DO  - 10.1016/S0021-9673(99)00335-0
AB  - The chiral separation of peptide-like conjugates of jasmonic acid and of cucurbic acid isomers was investigated by liquid chromatography on Chiralpak AS and Nucleodex β-PM. The retention sequences reflect distinct chromatographic properties with respect to the chirality of the jasmonic acid part or of the cucurbic acid isomers. The chromatographic behaviour of the amide conjugates on a reversed-phase C18 column provides evidence for the resolution of diastereomeric conjugates depending on the chirality of both constituents of the conjugate molecule. The chromatographic procedures are suitable for the analytical and preparative separation of such conjugates.
A2  - 
C1  - Molecular Signal Processing; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2311
TI  - Analysis of synthetic isoleucine conjugates of cucurbic acid isomers by liquid chromatography
JO  - Phytochem. Anal.
PY  - 1999
SP  - 82-87
AU  - Kramell, R.
AU  - Porzel, A.
AU  - Miersch, O.
AU  - Schneider, G.
AU  - 
VL  - 10
UR  - 
DO  - 10.1002/(SICI)1099-1565(199903/04)10:2&lt;82::AID-PCA448&gt;3.0.CO;2-K
AB  - Conjugates of 3,7‐trans  cucurbic acid isomers with either (S )‐ or (R )‐isoleucine were synthesised from the diastereomeric conjugate of (3R , 7R )‐jasmonic acid and (3S , 7S )‐jasmonic acid by sodium borohydride reduction. The resulting diastereomers were characterised by nuclear magnetic resonance spectra. The authentic substances were subjected to liquid chromatography using a reversed‐phase C18 matrix and the chiral stationary phase Chiralpak AS. For all (6RS )‐hydroxy epimeric pairs, a baseline separation could be observed. The elution sequences obtained indicate that the 3,6‐trans  oriented epimers with (S )‐isoleucine elute prior to the 3,6‐cis  configured individuals independent of the mode of chromatography. In contrast, the elution pattern of the conjugates containing (R )‐isoleucine was reversed on the chiral stationary phase. The epimers with a 3,6‐cis  configured hydroxy group and the acid side chain eluted faster than those with the 3,6‐trans  configuration. The chromatographic conditions described are suitable for resolving mixtures of isomeric N‐(cucurbinoyl)‐isoleucines in order to assign their stereochemistry and to obtain chiral reference materials on a preparative scale.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2306
TI  - Accumulation of phthalides in elicitor-treated cell suspension cultures of Petroselinum crispum
JO  - Phytochemistry
PY  - 1999
SP  - 629-635
AU  - Hagemeier, J.
AU  - Batz, O.
AU  - Schmidt, J.
AU  - Wray, V.
AU  - Hahlbrock, K.
AU  - Strack, D.
AU  - 
VL  - 51
UR  - 
DO  - 10.1016/S0031-9422(99)00072-2
AB  - The present study describes the effect of a Phytophthora sojae 25-amino acid oligopeptide (Pep25) elicitor on the secondary metabolism of parsley cell cultures (Petroselinum crispum L.). HPLC analysis of the accumulated compounds in the elicitor-treated cultures revealed the expected accumulation of furanocoumarins (e.g. marmesin and bergapten) as well as various non-coumarin compounds which have not been described previously to occur in this cell culture. These compounds were isolated by preparative HPLC and identified by spectroscopic methods (MS, NMR) as 5-hydroxy- and 7-hydroxy-3-butylidenephthalides including two novel conjugates of the 7-hydroxy derivative, i.e. 7-O-glucoside and 7-O-(6′-malonylglucoside).
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2302
TI  - Development and Validation of a Homology Model of Human Cathepsin H Including the Mini-Chain
JO  - J. Mol. Model.
PY  - 1999
SP  - 177-188
AU  - Fengler, A.
AU  - Brandt, W.
AU  - 
VL  - 5
UR  - 
DO  - 10.1007/s008940050117
AB  - Cathepsin H is involved in intracellular protein degradation and is implicated in a variety of physiological processes such as proenzyme activation, enzyme inactivation, hormone maturation, tissue remodeling, and bone matrix resorption. A model of the tertiary structure of the human lysosomal cysteine protease cathepsin H was constructed. The protein structure was built from its amino acid sequence and its homology to papain, actinidin, and cathepsin L for which crystallographic co-ordinates are available. The model was generated using the COMPOSER module of SYBYL.The position and interaction behavior of the so called mini-chain, the octapeptide EPQNCSAT, to the active-site cleft of cathepsin H could be determined by docking studies. Refinement was achieved through interactive visual and algorithmic analysis and minimization with the TRIPOS force field. The model was found to correlate with observed empirical data regarding ligand specificity. The model defines possible steric, hydrophobic, and electrostatic interactions. We anticipate that the model will serve as a tool to understand substrate specificity and may be used for the development of new specific ligands.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2301
TI  - Conformational studies of two new brassinosteroid analogues with a 22,23-trans diol function
JO  - J. Chem. Soc., Perkin Trans. 2
PY  - 1999
SP  - 233-238
AU  - Drosihn, S.
AU  - Porzel, A.
AU  - Voigt, B.
AU  - Brandt, W.
AU  - Wagner, C.
AU  - Merzweiler, K.
AU  - Adam, G.
AU  - 
VL  - 1999
UR  - 
DO  - 10.1039/A807440B
AB  - 22,24-Diepiteasterone (3) and 23,24-diepiteasterone (4) were synthesized starting from a mixture of the corresponding (22S,23S)- and (22R,23R)-epoxides. Using detailed NOE investigations and molecular dynamic simulations with explicit solvent, the preferred conformations of both compounds were determined in solution. For both compounds 3 and 4 a preferred conformation of the side chain was found. For 4, by X-ray analysis the conformation in crystalline state was determined which differs distinctly from that in solution.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2299
TI  - Antidesmone, a novel type isoquinoline alkaloid from Antidesma membranaceum (Euphorbiaceae)
JO  - Tetrahedron
PY  - 1999
SP  - 1079-1086
AU  - Buske, A.
AU  - Busemann, S.
AU  - Mühlbacher, J.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Bringmann, G.
AU  - Adam, G.
AU  - 
VL  - 55
UR  - 
DO  - 10.1016/S0040-4020(98)01107-7
AB  - A novel type of tetrahydroisoquinoline alkaloid, antidesmone (1), was isolated from Antidesma membranaceum Müll. Arg.. The structure of 1 was determined to be (5S)-1-hydroxy-4-methoxy-3-methyl-5-octyl-5,6,7,8-tetrahydroisoquinolin-8-one by spectroscopic methods (MS, 1H, 13C 2D NMR, CD) and chemical derivatisation. The absolute (S)-configuration was determined by quantumchemical calculation of CD spectra.Antidesmone (1), a novel type of tetrahydroisoquinoline alkaloid, was isolated from Antidesma membranaceum Müll. Arg. The structure of 1 was determined to be (5S)-1-hydroxy-4-methyl-5-octyl-5,6,7,8-tetrahydroisoquinolin-8-one.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2297
TI  - A molecular mechanism for the cleavage of a disulfide bond as the primary function of agonist binding to G-protein-coupled receptors based on theoretical calculations supported by experiments
JO  - Eur. J. Biochem.
PY  - 1999
SP  - 89-97
AU  - Brandt, W.
AU  - Golbraikh, A.
AU  - Tager, M.
AU  - Lendeckel, U.
AU  - 
VL  - 261
UR  - 
DO  - 10.1046/j.1432-1327.1999.00224.x
AB  - A model of the binding site of δ‐opioids in the extracellular region of the G‐protein‐coupled opioid receptor based on modelling studies is presented. The distance between Asp288 and the disulfide bridge (Cys121–Cys198) formed between the first and second extracellular loops was found to be short. This model is consistent with site‐directed mutagenesis studies. The arrangement of the ligands found in the receptor led to the development of a reaction mechanism for the cleavage of the disulfide bond catalysed by the ligands. Semi‐empirical quantum chemical PM3 and AM1 calculations as well as ab initio  studies showed that the interaction between the carboxylic acid side chain of aspartic acid and the disulfide bond leads to the polarization of, and withdrawal of a proton from, the protonated nitrogen of the ligand to one of the sulfur atoms. A mixed sulfenic acid and carboxylic acid anhydrate is formed as an intermediate as well as a thiol. The accompanying cleavage of the disulfide bond may produce a conformational change in the extracellular loops such that the pore formed by the seven‐helix bundle opens allowing entrance of the ligand, water and ions into the cell. Cleavage of the disulfide bond after opioid administration was demonstrated experimentally by flow‐cytometric measurements employing CMTMR and monobromobimane‐based analyses of membrane‐located thiols. The suggested mechanism may explain, in a consistent way, the action of agonists and antagonists and is assumed to be common for many G‐protein coupled receptors.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2296
TI  - Lewis Acid Mediated Selective Chalcogenalkylation of Silyl Enol Ethers with [O,S]-Acetals
JO  - Synthesis
PY  - 1999
SP  - 562-564
AU  - Braga, A. L.
AU  - Dornelles, L.
AU  - Silveira, C. C.
AU  - Wessjohann, L. A.
AU  - 
VL  - 1999
UR  - 
DO  - 10.1055/s-1999-3429
AB  - Silyl enol ethers of ketones were selectively alkylated with [O,S]-acetals mediated by Lewis acid in a Mukaiyama type Aldol reaction. The products were β-alkoxy- and /or β-sulfanyl carbonyl compounds depending on the catalyst employed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2295
TI  - A new functionalized, chiral disulfide derived from L-cysteine: (R,R)-bis[(3-benzyloxazolan-4-yl)-methane] disulfide as a catalyst in the diethylzinc addition to aldehydes
JO  - Tetrahedron: Asymmetry
PY  - 1999
SP  - 1733-1738
AU  - Braga, A. L.
AU  - Appelt, H. R.
AU  - Schneider, P. H.
AU  - Silveira, C. C.
AU  - Wessjohann, L. A.
AU  - 
VL  - 10
UR  - 
DO  - 10.1016/S0957-4166(99)00145-7
AB  - A new, easily accessible, chiral disulfide 3 was prepared from l-cysteine in a short synthetic sequence (Scheme. 1) and applied successfully as a highly efficient catalyst for the enantioselective addition of diethyl zinc to aromatic and aliphatic aldehydes to afford the product alcohols in up to more than 99% ee. In contrast to the more common amino alcohols used in similar reactions, catalyst 3 does not have a protic hydrogen in the form of a free hydroxy group.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2293
TI  - Coumarins from Hypericum keniense (Guttiferae)
JO  - Pharmazie
PY  - 1999
SP  - 235-236
AU  - Ang'edu, C. A.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Gitu, P.
AU  - Midiwo, J. O.
AU  - Adam, G.
AU  - 
VL  - 54
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2340
TI  - Monitoring brassinosteroid biosynthetic enzymes by fluorescent tagging and HPLC analysis of their substrates and products
JO  - Phytochemistry
PY  - 1999
SP  - 237-242
AU  - Winter, J.
AU  - Schneider, B.
AU  - Meyenburg, S.
AU  - Strack, D.
AU  - Adam, G.
AU  - 
VL  - 51
UR  - 
DO  - 10.1016/S0031-9422(98)00760-2
AB  - Both the vicinal side chain hydroxyl groups and the 6-oxo function of brassinosteroids were modified by fluorescence tagging. Dansylaminophenylboronic acid was used as a derivatizing agent to form fluorescent esters of brassinosteroids containing a side-chain cis-diol structure. 6-Oxo type brassinosteroids were derivatized by means of dansylhydrazine. The modified brassinosteroids, as far as possible derivatized both at the diol and the oxo group, were separated by HPLC and the optimal emission wavelength was determined. By this approach almost all brassinosteroids, including biosynthetic precursors, were susceptible to highly sensitive analysis in the fmol range. This method has been verified as an analytical tool to determine brassinosteroids in cell culture extracts and to monitor brassinosteroid biosynthetic enzymes. 24-Epibrassinolide has been detected in tomato cell suspension cultures. Several steps of brassinosteroid biosynthesis, including the Baeyer–Villiger oxidation of 24-epicastasterone to give 24-epibrassinolide, were monitored in vitro with protein preparations of the same cell culture line.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2339
TI  - Recent Advances in Chromium(II)- and Chromium(III)-Mediated Organic Synthesis
JO  - Synthesis
PY  - 1999
SP  - 1-36
AU  - Wessjohann, L. A.
AU  - Scheid, G.
AU  - 
VL  - 1999
UR  - 
DO  - 10.1055/s-1999-3672
AB  - Synthetic transformations utilizing chromium(II) or chromium(III) reagents, mainly C-C-coupling reactions, are discussed. Chromium reagents find increasing application in complex total syntheses where other organometallics are difficult to apply. They are easy to prepare and exhibit extraordinary chemoselectivity and high diastereoselectivity. In this article emphasis is laid on recent results in synthetic procedures, on little known general aspects of (organo)chromium chemistry, and on areas not reviewed before. The most important recent advances include reactions catalytic in chromium ions, anti-selective Reformatsky-type aldol reactions with excellent asymmetric induction, domino radical/carbanion reactions, asymmetric chromium(III) catalyzed epoxide openings and homogeneous alkene polymerization catalysts. Some progress is also made in ligand controlled enantioselective reactions with Cr(II) reagents, but satisfying solutions remain a major challenge in the field.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2338
TI  - Phenylpropanoids in mycorrhizas of the Pinaceae
JO  - Planta
PY  - 1999
SP  - 491-502
AU  - Weiss, M.
AU  - Schmidt, J.
AU  - Neumann, D.
AU  - Wray, V.
AU  - Christ, R.
AU  - Strack, D.
AU  - 
VL  - 208
UR  - 
DO  - 10.1007/s004250050586
AB  - Tissue-specific accumulation of phenylpropanoids was studied in mycorrhizas of the conifers, silver fir (Abies alba Mill.), Norway spruce [Picea abies (L.) Karst.], white pine (Pinus strobus L.), Scots pine (Pinus silvestris L.), and Douglas fir [Pseudotsuga menziesii (Mirbel) Franco], using high-performance liquid chromatography and histochemical methods. The compounds identified were soluble flavanols (catechin and epicatechin), proanthocyanidins (mainly dimeric catechins and/or epicatechins), stilbene glucosides (astringin and isorhapontin), one dihydroflavonol glucoside (taxifolin 3′-O-glucopyranoside), and a hydroxycinnamate derivative (unknown ferulate conjugate). In addition, a cell wall-bound hydroxycinnamate (ferulate) and a hydroxybenzaldehyde (vanillin) were analysed. Colonisation of the root by the fungal symbiont correlated with the distribution pattern of the above phenylpropanoids in mycorrhizas suggesting that these compounds play an essential role in restricting fungal growth. The levels of flavanols and cell wall-bound ferulate within the cortex were high in the apical part and decreased to the proximal side of the mycorrhizas. In both Douglas fir and silver fir, which allowed separation of inner and outer parts of the cortical tissues, a characteristic transversal distribution of these compounds was found: high levels in the inner non-colonised part of the cortex and low levels in the outer part where the Hartig net is formed. Restriction of fungal growth to the outer cortex may also be achieved by characteristic cell wall thickening of the inner cortex which exhibited flavanolic wall infusions in Douglas fir mycorrhizas. Long and short roots of conifers from natural stands showed similar distribution patterns of phenylpropanoids and cell wall thickening compared to the respective mycorrhizas. These results are discussed with respect to co-evolutionary adaptation of both symbiotic partners regarding root structure (anatomy) and root chemistry.
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2337
TI  - Light-induced betacyanin and flavonol accumulation in bladder cells of Mesembryanthemum crystallinum
JO  - Phytochemistry
PY  - 1999
SP  - 583-592
AU  - Vogt, T.
AU  - Ibdah, M.
AU  - Schmidt, J.
AU  - Wray, V.
AU  - Nimtz, M.
AU  - Strack, D.
AU  - 
VL  - 52
UR  - 
DO  - 10.1016/S0031-9422(99)00151-X
AB  - Treatment of the halophyte Mesembryanthemum crystallinum L. (ice plant) (Aizoaceae) with high intensities of white light resulted in a rapid cell-specific accumulation of betacyanins and flavonoids with 6-methoxyisorhamnetin 3-O-{[(2‴-E-feruloyl)-3‴-O-(β-d-glucopyranosyl)](2″-O-β-d-xylopyranosyl)}-β-d-glucopyranoside (mesembryanthin) as the predominant component, within bladder cells of the leaf epidermis. Induced accumulation of these metabolites was first detected 18 h after the initiation of light treatment in bladder cells located at the tip of young leaves followed by the bladder cells located on the epidermis of fully expanded leaves. UV-A light apparently is sufficient to induce accumulation of betacyanins and flavonoids. Application of 2-aminoindan 2-phosphonic acid, a specific inhibitor of phenylalanine ammonia-lyase (PAL; EC 4.3.1.5), not only inhibited the accumulation of flavonoids but also reduced betacyanin formation. Based on these observations we suggest these bladder cells as a model system to study regulation of betacyanin and flavonoid biosyntheses.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2334
TI  - Counlarins, limonoids and an alkaloid from Clausena excavata
JO  - Phytochemistry
PY  - 1999
SP  - 511-516
AU  - Thuy, T. T.
AU  - Ripperger, H.
AU  - Porzel, A.
AU  - Sung, T. V.
AU  - Adam, G.
AU  - 
VL  - 52
UR  - 
DO  - 10.1016/S0031-9422(99)00122-3
AB  - In addition to a known alkaloid, some limonoids and coumarins, the new coumarins excavatins A–M have been isolated from Clausena excavata. Their structures have been assigned by NMR and CD investigations.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2333
TI  - Bishordeninyl terpene alkaloids from Zanthoxylum avicennae
JO  - Phytochemistry
PY  - 1999
SP  - 903-907
AU  - Thuy, T. T.
AU  - Porzel, A.
AU  - Ripperger, H.
AU  - Sung, T. V.
AU  - Adam, G.
AU  - 
VL  - 50
UR  - 
DO  - 10.1016/S0031-9422(98)00612-8
AB  - In addition to (−)-culantraramine and (−)-culantraraminol the bishordeninyl terpene alkaloids, (−)-culantraramine N-oxide, (−)-culantraraminol N-oxide and avicennamine, have been isolated from the leaves of Zanthoxylum avicennae. Their structures have been assigned by MS and especially by NMR investigations.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2331
TI  - Conformational and configurational behaviour of κ-agonistic 3,7-diazabicyclo[3.3.1]nonan-9-ones—synthesis, nuclear magnetic resonance studies and semiempirical PM3 calculations
JO  - J. Chem. Soc., Perkin Trans. 2
PY  - 1999
SP  - 1827-1834
AU  - Siener, T.
AU  - Holzgrabe, U.
AU  - Drosihn, S.
AU  - Brandt, W.
AU  - 
VL  - 1999
UR  - 
DO  - 10.1039/A806641H
AB  - 2,4-Diaryl substituted 3,7-diazabicyclo[3.3.1]nonan-9-one 1,5-diesters were found to have a high affinity for κ-opioid receptors. To develop highly potent analgesics, the purpose of this study was the synthesis and the structural characterisation of the novel 2,4-bis(4-nitrophenyl), 2,4-bis(3-nitrophenyl), 2,4-bis(4-quinolyl), 2,4-bis(2-quinolyl), 2,4-bis(1-naphthyl) and 2,4-bis(2-naphthyl) substituted 3,7-diazabicyclo[3.3.1]nonan-9-one 1,5-diesters by means of NMR spectroscopy and molecular modelling. It could be proved that several derivatives undergo trans–cis-isomerisation of the aromatic rings linked to the rigid skeleton whereas others show rotational isomerisation. Semiempirical quantum-chemical PM3 calculations were performed to analyse the thermodynamic stability of the isomers as well as the mechanism of the trans–cis- or cis–trans-conversion.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2329
TI  - Light-induced cytochrome P450-dependent enzyme in indole alkaloid biosynthesis: tabersonine 16-hydroxylase
JO  - FEBS Lett.
PY  - 1999
SP  - 97-102
AU  - Schröder, G.
AU  - Unterbusch, E.
AU  - Kaltenbach, M.
AU  - Schmidt, J.
AU  - Strack, D.
AU  - De Luca, V.
AU  - Schröder, J.
AU  - 
VL  - 458
UR  - 
DO  - 10.1016/S0014-5793(99)01138-2
AB  - Vinblastine and vincristine are two medically important bisindole alkaloids from Catharanthus roseus (Madagascar periwinkle). Attempts at production in cell cultures failed because a part of the complex pathway was not active, i.e. from tabersonine to vindoline. It starts with tabersonine 16-hydroxylase (T16H), a cytochrome P450-dependent enzyme. We now show that T16H is induced in the suspension culture by light and we report the cloning of the cDNA. The enzyme was expressed in Escherichia coli as translational fusion with the P450 reductase from C. roseus, and the reaction product was identified by mass spectrometry. The protein (CYP71D12) shares 47–52% identity with other members of the CYP71D subfamily with unknown function. The induction by light was strongly enhanced by a nutritional downshift (transfer into 8% aqueous sucrose). We discuss the possibility that the entire pathway to bisindoles can be expressed in suspension cultures.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2328
TI  - Cloning and Expression of a Potato cDNA Encoding Hydroxycinnamoyl-CoA:Tyramine N-(Hydroxycinnamoyl)transferase
JO  - J. Biol. Chem.
PY  - 1999
SP  - 4273-4280
AU  - Schmidt, A.
AU  - Grimm, R.
AU  - Schmidt, J.
AU  - Scheel, D.
AU  - Strack, D.
AU  - Rosahl, S.
AU  - 
VL  - 274
UR  - 
DO  - 10.1074/jbc.274.7.4273
AB  - Hydroxycinnamoyl-CoA:tyramineN-(hydroxycinnamoyl)transferase (THT; EC 2.3.1.110) catalyzes the transfer of hydroxycinnamic acids from the respective CoA esters to tyramine and other amines in the formation ofN-(hydroxycinnamoyl)amines. Expression of THT is induced byPhytophthora infestans, the causative agent of late blight disease in potato. The amino acid sequences of nine endopeptidase LysC-liberated peptides from purified potato THT were determined. Using degenerate primers, a THT-specific fragment was obtained by reverse transcription-polymerase chain reaction, and THT cDNA clones were isolated from a library constructed from RNA of elicitor-treated potato cells. The open reading frame encoding a protein of 248 amino acids was expressed in Escherichia coli. Recombinant THT exhibited a broad substrate specificity, similar to that of native potato THT, accepting cinnamoyl-, 4-coumaroyl-, caffeoyl-, feruloyl- and sinapoyl-CoA as acyl donors and tyramine, octopamine, and noradrenalin as acceptors tested. Elicitor-induced THT transcript accumulation in cultured potato cells peaked 5 h after initiation of treatment, whereas enzyme activity was highest from 5 to 30 h after elicitation. In soil-grown potato plants, THT mRNA was most abundant in roots. Genomic Southern analyses indicate that, in potato, THT is encoded by a multigene family.
A2  - 
C1  - Bioorganic Chemistry; Biochemistry of Plant Interactions; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2325
TI  - Characteristics of the phloem path: analysis and distribution of carbohydrates in the petiole of Cyclamen
JO  - J. Exp. Bot.
PY  - 1999
SP  - 1807-1816
AU  - Rothe, K.
AU  - Porzel, A.
AU  - Neumann, S.
AU  - Grimm, E.
AU  - 
VL  - 50
UR  - 
DO  - 10.1093/jxb/50.341.1807
AB  - Compartmentation fluxes of carbohydrates along the phloem path were analysed in the petiole of Cyclamen persicum (L.) Mill. Sucrose represented the dominant fraction (58–75% of soluble carbohydrates in the vascular symplast). Planteose (12–22%), glucose (3–8%) and fructose (3–13%) occurred in lower amounts (data from liquid chromatography, percentages of the total peak area). Starch was not detectable. Upon feeding leaves with 14CO2, 98% and 90% of radiolabel was recovered as sucrose in the vascular symplast after 3 h and 24 h, respectively. Thus, sucrose appeared to be the exclusive transport sugar in Cyclamen. Experiments with asymmetrically labelled sucrose revealed that there was no metabolism of translocated sucrose. Analysis of six consecutive petiole segments (each 2 cm in length) showed a homogeneous longitudinal distribution of sucrose and planteose. The lateral distribution of these sugars differed markedly. On average, the sucrose concentration amounted to 4.7 and 0.4 mg g−1 FM in the vascular apoplast and petiole parenchyma, respectively. Sucrose was unloaded without hydrolysis and stored in the periphery of the phloem path. Planteose was identified as another storage saccharide. Sucrose synthesis by sucrose phosphate synthase occurred when isolated vascular bundles were incubated with [14C]glucose or [14C]fructose. These data suggest that the phloem path is characterized by both source and sink like activity.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2324
TI  - β-Carboline alkaloids from Hedyotis capitellata
JO  - Phytochemistry
PY  - 1999
SP  - 1725-1729
AU  - Phuong, N. M.
AU  - Van Sung, T.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Merzweiler, K.
AU  - Adam, G.
AU  - 
VL  - 52
UR  - 
DO  - 10.1016/S0031-9422(99)00280-0
AB  - Three new β-carboline alkaloids were isolated from Hedyotis capitellata (Rubiaceae). Their structures were elucidated by spectroscopic data and X-ray analysis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2323
TI  - Two New β-Carboline Alkaloids from Hedyotis capitellata var. mollis
JO  - Planta Med.
PY  - 1999
SP  - 761-762
AU  - Phuong, N. M.
AU  - Sung, T. V.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Adam, G.
AU  - 
VL  - 65
UR  - 
DO  - 10.1055/s-2006-960861
AB  - Two new β-carboline alkaloids, hedyocapitelline and hedyocapitine, were isolated from Hedyotis capitellata var. mollis (Rubiaceae). Their structures were elucidated by spectroscopic data 1H- and 13C-NMR, MS, IR, UV).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 170
TI  - Enzymatic C-C-Coupling: The Development of Aromatic Prenylation for Organic Synthesis
T2  - Bioorganic Chemistry: Highlights and New Aspects
PB  - 
PY  - 1999
SP  - 79-88
AU  - Wessjohann, L. A.
AU  - Sontag, B.
AU  - Dessoy, M. A.
AU  - 
VL  - 
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 169
TI  - Brassinosteroids
T2  - 
PB  - Fortschritte der Chemie organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products
PY  - 1999
SP  - 1-46
AU  - Adam, G.
AU  - Schmidt, J.
AU  - Schneider, B.
AU  - 
VL  - 78
UR  - 
SN  - 978-3-7091-6394-8
DO  - 10.1007/978-3-7091-6394-8_1
AB  - It was in 1979 when GROVE et al. isolated from pollen of rape (Brassica napus) a highly active plant growth promoter, named it brassinolide and elucidated its structure as (22R,23R,24S)-2α,3α, 22,23-tetrahydroxy-24-methyl-B-homo-6a-oxa-5α-cholestan-6-one (1) by spectroscopic methods including X-ray analysis (1). The original structural features of this compound and its unique high biological activity at very low concentrations stimulated intense research activities in many laboratories. Such efforts were directed towards the search for similar compounds in the plant kingdom, their chemical synthesis, biochemistry and biological mode of action leading up to their practical application in agriculture and horticulture. As a result of this interdisciplinary and rapidly processing research, brassinosteroids can nowadays be regarded as a new class of plant hormones with ubiquitous occurrence in the plant kingdom. Especially, recent molecular biological studies demonstrated their essential role for normal plant growth and development. A series of reviews have been published (2–11). Whereas the first book on brassinosteroid research covers developments up to 1990 (12), two up-to-date publications about this topic have appeared very recently (13, 14). The present article covers the literature up to December 1998 with special consideration of phytochemical, analytical and biochemical aspects.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2377
TI  - Benzeneselenenyl Reagents in Organic Synthesis
JO  - J. Prakt. Chem.
PY  - 1998
SP  - 189-203
AU  - Wessjohann, L. A.
AU  - Sinks, U.
AU  - 
VL  - 340
UR  - 
DO  - 10.1002/prac.19983400302
AB  - An account of the most commonly used reagents for the introduction of the benzeneselenyl (phenyl seleno) group is given. The review focuses on the various methods of its introduction as auxiliary, modifying or protective entity, and its subsequent removal, thereby often promoting other reactions as cyclizations or double bond formation. Less emphasis is laid on reactions of the phenylselenenylated intermediates with the PhSe‐group left intact utilizing its stabilizing properties on charged intermediates, on reagents with a modified phenyl group, e.g.  chiral derivatives, or on reactions not involving intermediate CSe‐bond formation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2372
TI  - Chalcones and ecdysteroids from Vitex leptobotrys
JO  - Phytochemistry
PY  - 1998
SP  - 2603-2605
AU  - Thuy, T. T.
AU  - Porzel, A.
AU  - Ripperger, H.
AU  - Sung, T. V.
AU  - Adam, G.
AU  - 
VL  - 49
UR  - 
DO  - 10.1016/S0031-9422(98)00411-7
AB  - In addition to some known chalcones and ecdysteroids three new chalcones have been isolated from aerial parts of Vitex leptobotrys, the structures of which have been identified as 2′,4′-dihydroxy-4,6′-dimethoxychalcone, 4′-hydroxy-4,2′,6′-trimethoxychalcone and 4,2′,4′,β-tetrahydroxy-6′-methoxy-α,β-dihydrochalcone, respectively.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2371
TI  - Plant Polyketide Synthases: A Chalcone Synthase-Type Enzyme Which Performs a Condensation Reaction with Methylmalonyl-CoA in the Biosynthesis of C-Methylated Chalcones
JO  - Biochemistry
PY  - 1998
SP  - 8417-8425
AU  - Schröder, J.
AU  - Raiber, S.
AU  - Berger, T.
AU  - Schmidt, A.
AU  - Schmidt, J.
AU  - Soares-Sello, A. M.
AU  - Bardshiri, E.
AU  - Strack, D.
AU  - Simpson, T. J.
AU  - Veit, M.
AU  - Schröder, G.
AU  - 
VL  - 37
UR  - 
DO  - 10.1021/bi980204g
AB  - Heterologous screening of a cDNA library from Pinus strobus seedlings identified clones for two chalcone synthase (CHS) related proteins (PStrCHS1 and PStrCHS2, 87.6% identity). Heterologous expression in Escherichia coli showed that PStrCHS1 performed the typical CHS reaction, that it used starter CoA-esters from the phenylpropanoid pathway, and that it performed three condensation reactions with malonyl-CoA, followed by the ring closure to the chalcone. PstrCHS2 was completely inactive with these starters and also with linear CoA-esters. Activity was detected only with a diketide derivative (N-acetylcysteamine thioester of 3-oxo-5-phenylpent-4-enoic acid) that corresponded to the CHS reaction intermediate postulated after the first condensation reaction. PstrCHS2 performed only one condensation, with 6-styryl-4-hydroxy-2-pyrone derivatives as release products. The enzyme preferred methylmalonyl-CoA against malonyl-CoA, if only methylmalonyl-CoA was available. These properties and a comparison with the CHS from Pinussylvestris suggested for PstrCHS2 a special function in the biosynthesis of secondary products. In contrast to P. sylvestris, P. strobus contains C-methylated chalcone derivatives, and the methyl group is at the position predicted from a chain extension with methylmalonyl-CoA in the second condensation of the biosynthetic reaction sequence. We propose that PstrCHS2 specifically contributes the condensing reaction with methylmalonyl-CoA to yield a methylated triketide intermediate. We discuss a model that the biosynthesis of C-methylated chalcones represents the simplest example of a modular polyketide synthase.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2369
TI  - Brassinosteroids and a pregnane glucoside from Daucus carota
JO  - Phytochem. Anal.
PY  - 1998
SP  - 14-20
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Adam, G.
AU  - 
VL  - 9
UR  - 
DO  - 10.1002/(SICI)1099-1565(199801/02)9:1&lt;14::AID-PCA381&gt;3.0.CO;2-4
AB  - The brassinosteroids brassinolide, castasterone and 24‐epi‐castasterone could be isolated and identified from seeds of Daucus carota . Furthermore, a new pregnanolone glucoside was identified as β‐D ‐glucopyranosyl‐(1‐2)‐β‐D ‐glucopyranosyl‐3β‐hydroxy‐5α‐pregnane‐20‐one (sophorosylpregnanolone) by nuclear magnetic resonance spectroscopy, liquid chromatography‐mass spectrometry and gas chromatography‐mass spectrometry.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2368
TI  - 3α,20-dihydroxy-3β,25-epoxylupane, a triterpene from Rhus typhina
JO  - Phytochemistry
PY  - 1998
SP  - 2049-2051
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Adam, G.
AU  - 
VL  - 49
UR  - 
DO  - 10.1016/S0031-9422(98)00398-7
AB  - A new triterpene, 3α,20-dihydroxy-3β,25-epoxylupane, was isolated and structurally elucidated from flowers of the sumach tree Rhus typhina (Anacardiaceae).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2363
TI  - Photochemistry of Artemisinin Derivatives
JO  - Nat. Prod. Lett.
PY  - 1998
SP  - 151-159
AU  - Quan, T. D.
AU  - Porzel, A.
AU  - Ripperger, H.
AU  - Sung, T. V.
AU  - Adam, G.
AU  - 
VL  - 12
UR  - 
DO  - 10.1080/10575639808048285
AB  - Photochemical reactivity of some oxoalkyl derivatives of dihydroartemisinin as well as the reaction of dihydroartemisinin with lead tetraacetate/iodine under visible light have been studied.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2362
TI  - Capitelline - A New Indole Alkaloid from Hedyotis capitellata
JO  - Nat. Prod. Lett.
PY  - 1998
SP  - 93-100
AU  - Phuong, N. M.
AU  - Sung, T. V.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Adam, G.
AU  - 
VL  - 11
UR  - 
DO  - 10.1080/10575639808041203
AB  - A new indole monoterpene alkaloid, named capitelline (1), was isolated from Hedyotis capitellata (Rubiaceae). Its structure was elucidated by spectroscopic data (1H- and 13C-NMR, MS, IR, UV).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2359
TI  - 1H NMR conformational study on n-terminal nonapeptide sequences of HIV-1 Tat protein: a contribution to structure–activity relationships
JO  - J. Pept. Sci.
PY  - 1998
SP  - 400-410
AU  - Mrestani-Klaus, C.
AU  - Fengler, A.
AU  - Brandt, W.
AU  - Faust, J.
AU  - Wrenger, S.
AU  - Reinhold, D.
AU  - Ansorge, S.
AU  - Neubert, K.
AU  - 
VL  - 4
UR  - 
DO  - 10.1002/(SICI)1099-1387(199809)4:6&lt;400::AID-PSC162&gt;3.0.CO;2-G
AB  - On the basis of our recent results, the N‐terminal sequence of HIV‐1 Tat protein as a natural competitive inhibitor of dipeptidyl peptidase IV (DP IV) is supposed to interact directly with the active site of DP IV hence mediating its immunosuppressive effects via specific DP IV interactions. Of special interest is the finding that amino acid substitutions of the Tat(1–9) peptide (MDPVDPNIE) in position 5 with S‐isoleucine and in position 6 with S‐leucine led to peptides with strongly reduced inhibitory activity suggesting differences in the solution conformation of the three analogues. Therefore, 1H NMR techniques in conjunction with molecular modelling have been used here to determine the solution structure of Tat(1–9), I5‐Tat(1–9) and L6‐Tat(1–9) and to examine the influence of amino acid exchanges on structural features of these peptides. The defined structures revealed differences in the conformations what might be the reason for different interactions of these Tat(1–9) analogues with certain amino acids of the active site of DP IV.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2358
TI  - Cyclopeptide alkaloids of Scutia buxifolia
JO  - Phytochemistry
PY  - 1998
SP  - 125-129
AU  - Morel, A. F.
AU  - Machado, E. C. S.
AU  - Moreira, J. J.
AU  - Menezes, A. S.
AU  - Mostardeiro, M. A.
AU  - Zanatta, N.
AU  - Wessjohann, L. A.
AU  - 
VL  - 47
UR  - 
DO  - 10.1016/S0031-9422(97)00491-3
AB  - Two new peptide alkaloids, scutianines-K and -L were isolated from Scutia buxifolia, a plant growing in Brazil, Argentina and Uruguay. Their structures have been determined on the basis of spectroscopic studies. The stereochemistry of the N,N-dimethyl amino acid side-chain and the ring amino acid residues in both alkaloids have been assigned by gas chromatography employing modified cyclodextrins as chiral stationary phases.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2357
TI  - A jasmonic acid conjugate, N-[(—)-jasmonoyl]-tyramine, from Petunia pollen
JO  - Phytochemistry
PY  - 1998
SP  - 327-329
AU  - Miersch, O.
AU  - Knöfel, H.-D.
AU  - Schmidt, J.
AU  - Kramell, R.
AU  - Parthier, B.
AU  - 
VL  - 47
UR  - 
DO  - 10.1016/S0031-9422(97)00617-1
AB  - A new jasmonate, N-[(—)-jasmonoyl]-tyramine, was identified from petunia pollen in which (—)-jasmonic acid was detected and quantified.
A2  - 
C1  - Bioorganic Chemistry; Molecular Signal Processing
ER  - 


TY  - JOUR
ID  - 2355
TI  - Indole alkaloids from tabernaemontana bovina
JO  - Phytochemistry
PY  - 1998
SP  - 1457-1461
AU  - Lien, T. P.
AU  - Ripperger, H.
AU  - Porzel, A.
AU  - Merzweiler, K.
AU  - Sung, T. V.
AU  - Adam, G.
AU  - 
VL  - 49
UR  - 
DO  - 10.1016/S0031-9422(98)00127-7
AB  - In addition to (-)-mehranine, hecubine, ibogaine, ibogaline, 19R-epi voacristine, 20-hydroxyconopharyngine and pedunculine the novel indole alkaloids 3-oxomehranine and 14α,15β-dihydroxy-N-methylaspidospermine have been isolated from the leaves and stems of Tabernaemontana bovina. The structure of 3-oxomehranine has been assigned by NMR investigations, the structure of 14α,15β-dihydroxy-N-methylaspidospermine by X-ray analysis and their absolute configurations by circular dichroism.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2354
TI  - Constituents of Artocarpus tonkinensis
JO  - Pharmazie
PY  - 1998
SP  - 353
AU  - Lien, T. P.
AU  - Ripperger, H.
AU  - Porzel, A.
AU  - Sung, T. V.
AU  - Adam, G.
AU  - 
VL  - 53
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2353
TI  - Metabolic inversion of the 3-hydroxy function of brassinosteroids
JO  - Phytochemistry
PY  - 1998
SP  - 467-470
AU  - Kolbe, A.
AU  - Schneider, B.
AU  - Porzel, A.
AU  - Adam, G.
AU  - 
VL  - 48
UR  - 
DO  - 10.1016/S0031-9422(98)00037-5
AB  - Exogenously applied 3-dehydro-24-epi-teasterone is transformed by cell suspension cultures of Lycopersicon esculentum to give the metabolites 24-epi-teasterone and 24-epi-typhasterol in about equal but low quantities. The major portion of 24-epi-teasterone was found as carbohydrate conjugates while 24-epi-typhasterol occurred in free form, indicating significant influence of glycosidation on the equilibrium between both compounds. The importance of these conjugation processes for the regulation of the brassinosteroid biosynthesis is discussed.In tomato cell cultures, 3-dehydro-24-epi-teasterone is transformed both to 24-epi-teasterone and 24-epi-typhasterol. The ratio between both epimers is regulated by glycosidation in 3β-position
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2352
TI  - Anionic Tetranuclear Platina-β-diketonates of Platina-β-diketones – Organometallic Analogues of Platinum Blue Complexes
JO  - Eur. J. Inorg. Chem.
PY  - 1998
SP  - 1655-1659
AU  - Gerisch, M.
AU  - Bruhn, C.
AU  - Porzel, A.
AU  - Steinborn, D.
AU  - 
VL  - 1998
UR  - 
DO  - 10.1002/(SICI)1099-0682(199811)1998:11&lt;1655::AID-EJIC1655&gt;3.0.CO;2-7
AB  - The platina‐β‐diketone [Pt2{(COMe)2H}2(μ‐Cl)2] (1 ) reacts with aliphatic amines [n BuNH2, (i Pr)2NH, NEt3], N‐methylaniline, and N ,N‐dimethylaniline, as well as with strong bases, such as a proton sponge or [NMe4]OH, in an equimolar ratio to give the anionic platina‐β‐diketonato complexes of platina‐β‐diketones [BH]2[{Cl2Pt(μ‐COMe)2Pt[(COMe)2H]}2] (3 ) {B = n BuNH2 (3a ), (i Pr)2NH (3b ), NEt3 (3c ), PhNHMe (3d ), PhNMe2 (3e ), C10H6(NMe2)2 [1,8‐bis(dimethylamino)naphthalene] (3f ) and [NMe4]2[{Cl2Pt(μ‐COMe)2Pt[(COMe)2H]}2] (3g )}. All complexes were characterized by microanalysis, and by 1H‐NMR and IR spectroscopy. X‐ray structure analyses reveal that in the solid state the complexes 3a  · 0.5 CH2Cl2 and 3g  · 2 CH2Cl2 consist of tetranuclear dianions with zigzag Pt4 chains [Pt–Pt–Pt angle: 122.92(3)° (3a ), 119.30(6)° (3g )]. The central Pt···Pt distances [3a : 3.171(1) Å, 3g : 3.176(1) Å] give evidence for closed shell d8‐d8 interactions. Thus, these bis(acyl)‐bridged complexes can be regarded as organometallic analogues of platinum blue complexes.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2350
TI  - Three-dimensional structures of the cysteine proteases cathepsins K and S deduced by knowledge-based modelling and active site characteristics
JO  - Protein Eng. Des. Sel.
PY  - 1998
SP  - 1007-1013
AU  - Fengler, A.
AU  - Brandt, W.
AU  - 
VL  - 11
UR  - 
DO  - 10.1093/protein/11.11.1007
AB  - Human cathepsins K and S are recently identified proteins with high primary sequence homology to members of papain superfamily, including cathepsins B, L, H and papain. Models of the tertiary structures of cathepsins K and S and their complexes with a specific substrate and inhibitor were constructed and compared with the recently determined X-ray structure of cathepsin K. A major problem in the determination of the three-dimensional structure of proteins concerns the quality of the structural models obtained from the interpretation of experimental data. The framework of the tertiary structures of cathepsins K and S consisted of structurally conserved regions from the tertiary structure of the papain superfamily and the variable regions were constructed with fragments of other proteins from the protein data base. Based on docking studies the non-bonded interaction energies of ligands with the cathepsins were estimated. These energies correlate with experimentally determined substrate and inhibitory potency.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2349
TI  - Determination of the Solution Conformation of HIV-1 Tat(1–9) Peptides by Means of Molecular Dynamics Simulations Considering NMR Data and Docking Studies into an Active Site Model of DP IV
JO  - J. Mol. Model.
PY  - 1998
SP  - 200-210
AU  - Fengler, A.
AU  - Mrestani-Klaus, C.
AU  - Reinhold, D.
AU  - Wrenger, S.
AU  - Ansorge, S.
AU  - Faust, J.
AU  - Neubert, K.
AU  - Brandt, W.
AU  - 
VL  - 4
UR  - 
DO  - 10.1007/s0089480040200
AB  - The human immunodeficiency virus 1 Tat protein suppresses antigen-, anti-CD3-and mitogen-induced activation of human T cells when added to T cell cultures. This activity is important for the development of AIDS because lymphocytes from HIV-infected individuals exhibit a similar antigen-specific dysfunction. Moreover, Tat was found to interact with dipeptidyl peptidase IV (DP IV). To find out the amino acid sequence important for the inhibition of the DP IV enzymatic activity we investigated N-terminal Tat(1–9) peptide analogues with amino acid substitutions in different positions. Interestingly, the exchange of Pro6 with Leu and Asp5 with Ile strongly diminished the DP IV inhibition by Tat(1–9). Based on data derived from one-and two-dimensional 1H NMR investigations the solution conformations of the three nonapeptides in water were determined by means of molecular dynamics simulations. These conformations were used for studies of the docking behavior of the peptides into a model of the active site of DP IV. The results suggest that several attractive interactions between the native Tat(1–9) and DP IV lead to a stable complex and that the reduced affinity of both L6-Tat(1–9) and I5-Tat(1–9) derivatives might be caused by conformational alterations in comparison to the parent peptide.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2348
TI  - New pathway to polyketides in plants
JO  - Nature
PY  - 1998
SP  - 387-390
AU  - Eckermann, S.
AU  - Schröder, G.
AU  - Schmidt, J.
AU  - Strack, D.
AU  - Edrada, R. A.
AU  - Helariutta, Y.
AU  - Elomaa, P.
AU  - Kotilainen, M.
AU  - Kilpeläinen, I.
AU  - Proksch, P.
AU  - Teeri, T. H.
AU  - Schröder, J.
AU  - 
VL  - 396
UR  - 
DO  - 10.1038/24652
AB  - The repertoire of secondary metabolism (involving the production of compounds not essential for growth) in the plant kingdom is enormous, but the genetic and functional basis for this diversity is hard to analyse as many of the biosynthetic enzymes are unknown. We have now identified a key enzyme in the ornamental plant Gerbera hybrida (Asteraceae) that participates in the biosynthesis of compounds that contribute to insect and pathogen resistance. Plants transformed with an antisense construct of gchs2, a complementary DNA encoding a previously unknown function1,2, completely lack the pyrone derivatives gerberin and parasorboside. The recombinant plant protein catalyses the principal reaction in the biosynthesis of these derivatives: GCHS2 is a polyketide synthase that uses acetyl-CoA and two condensation reactions with malonyl-CoA to form the pyrone backbone of thenatural products. The enzyme also accepts benzoyl-CoA to synthesize the backbone of substances that have become of interest as inhibitors of the HIV-1 protease3,4,5. GCHS2 is related to chalcone synthase (CHS) and its properties define a new class of function in the protein superfamily. It appears that CHS-related enzymes are involved in the biosynthesis of a much larger range of plant products than was previously realized.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2378
TI  - Entwicklung einer Enzymatischen C-C-Verknüpfung: Die Prenylierung von Aromaten
JO  - GIT Labor-Fachzeitschrift
PY  - 1998
SP  - 229-230
AU  - Wessjohann, L. A.
AU  - Sontag, B.
AU  - 
VL  - 42
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2344
TI  - A uniform molecular model of δ opioid agonist and antagonist pharmacophore conformations
JO  - J. Comput. Aided Mol. Des.
PY  - 1998
SP  - 615-621
AU  - Brandt, W.
AU  - 
VL  - 12
UR  - 
DO  - 10.1023/A:1008003421291
AB  - On the basis of a model of the pharmacophore conformations of agonist of the δ-opioid receptor the corresponding δ-antagonist conformations were determined by means of force field calculations. The results explain the unusual behavior of several cyclic β-casomorphin analogues on the molecular level. Thus, for instance, the model helps to understand why Tyr-c[D-Orn-2-Nal-D-Pro-Gly] is a mixed μ-agonist and δ-antagonist. Furthermore, the model is consistent with low energy conformations of other δ-antagonists such as Tyr-Tic-Phe, Tyr-Tic-Phe-Phe, naltrindole and BNTX. The occupation of a special spatial area by bulky groups close to the protonated N-terminus of opioid peptides is assumed to be highly critical for the switch from agonist to antagonist behavior.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 179
TI  - The First Total Syntheses of Taxol
T2  - Organic Synthesis Highlights III
PB  - 
PY  - 1998
SP  - 295-305
AU  - Wessjohann, L. A.
AU  - 
VL  - 
UR  - 
SN  - 9783527619962
DO  - 10.1002/9783527619962.ch44
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 178
TI  - Characterization of Isoleucine Conjugates of Cucurbic Acid Isomers by Reversed-Phase and Chiral High-Performance Liquid Chromatography
T2  - Natural Product Analysis. Chromatography-Spectroscopy-Biological Testing
PB  - 
PY  - 1998
SP  - 77-78
AU  - Kramell, R.
AU  - Porzel, A.
AU  - Miersch, O.
AU  - Schneider, G.
AU  - 
VL  - 
UR  - https://de.book-info.com/isbn/3-528-06923-6.htm
AB  - 
A2  - 
C1  - Molecular Signal Processing; Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 176
TI  - Preferred Application of Coupling Reagents during Segment Condensation
T2  - Peptides 1998 (Proceedings of the 25th European Peptide Symposium)
PB  - 
PY  - 1998
SP  - 212-213
AU  - Griehl, C.
AU  - Hoffmann, F.
AU  - Brandt, W.
AU  - Plass, M.
AU  - 
VL  - 
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 175
TI  - Structural Elucidation of Oxygenated Triacylglycerols in Cucumber and Sunflower Cotyledons
T2  - Natural Product Analysis. Chromatography-Spectroscopy-Biological Testing
PB  - 
PY  - 1998
SP  - 57-58
AU  - Feussner, I.
AU  - Balkenhohl, T. J.
AU  - Porzel, A.
AU  - Kühn, H.
AU  - Wasternack, C.
AU  - 
VL  - 
UR  - https://de.book-info.com/isbn/3-528-06923-6.htm
AB  - 
A2  - 
C1  - Molecular Signal Processing; Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 173
TI  - HIV-1 Tat(1-9): Structure and Activity Studies
T2  - Peptides 1998 (Proceedings of the 25th European Peptide Symposium)
PB  - 
PY  - 1998
SP  - 580-581
AU  - Faust, J.
AU  - Mrestani-Klaus, C.
AU  - Fengler, A.
AU  - Brandt, W.
AU  - Wrenger, S.
AU  - Reinhold, D.
AU  - Ansorge, S.
AU  - Neubert, K.
AU  - 
VL  - 
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2423
TI  - The N-terminal Structure of HIV-1 Tat Is Required for Suppression of CD26-dependent T Cell Growth
JO  - J. Biol. Chem.
PY  - 1997
SP  - 30283-30288
AU  - Wrenger, S.
AU  - Hoffmann, T.
AU  - Faust, J.
AU  - Mrestani-Klaus, C.
AU  - Brandt, W.
AU  - Neubert, K.
AU  - Kraft, M.
AU  - Olek, S.
AU  - Frank, R.
AU  - Ansorge, S.
AU  - Reinhold, D.
AU  - 
VL  - 272
UR  - 
DO  - 10.1074/jbc.272.48.30283
AB  - Evidence exists that the human immunodeficiency virus-1 (HIV-1) transactivator Tat occurs extracellularly and is involved in the immunosuppression of non-HIV-1-infected T cells of acquired immunodeficiency syndrome (AIDS) patients. The mechanism of this immunosuppressive activity of Tat has been controversially discussed. Interestingly, Tat binds to the T cell activation marker CD26, which has been shown to play a key role in the regulation of growth of lymphocytes and to inhibit its dipeptidyl peptidase IV (DP IV) activity. Here we show that the N-terminal nonapeptide MDPVDPNIE of Tat is a competitive inhibitor of DP IV and suppresses DNA synthesis of tetanus toxoid-stimulated peripheral blood mononuclear cells. Amino acid exchanges at positions 5 and 6 strongly weaken these effects.1H nuclear magnetic resonance and molecular dynamics simulations of Tat(1–9), I5-Tat(1–9), and L6-Tat(1–9) suggest a similar backbone conformation for Tat(1–9) and L6-Tat(1–9). The solution conformation of I5-Tat(1–9) considerably differs from the other two. However, Tat(1–9) fits into our previously proposed active site model of DP IV in contrast to I5-Tat(1–9) and L6-Tat(1–9). Conformational alterations with regard to the parent peptide and spatial hindrances between these both compounds and DP IV can explain the loss of inhibitory activity. Our data suggest that the N-terminal residues of HIV-1 Tat do interact directly with the active site of DP IV and that DP IV does mediate Tat’s immunosuppressive effects.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2422
TI  - Role of a cytochrome P450-dependent monooxygenase in the hydroxylation of 24-epi-brassinolide
JO  - Phytochemistry
PY  - 1997
SP  - 233-237
AU  - Winter, J.
AU  - Schneider, B.
AU  - Strack, D.
AU  - Adam, G.
AU  - 
VL  - 45
UR  - 
DO  - 10.1016/S0031-9422(96)00827-8
AB  - 24-epi-Brassinolide, exogenously applied to cell suspension cultures of Lycopersicon esculentum is hydroxylated at C-25 and C-26, respectively, followed by glucosylation of the newly formed hydroxyl group. Treatment of the cell cultures with the specific cytochrome P450 inhibitors, clotrimazole and ketoconazole, resulted in a strong decrease of only the C-25 hydroxylation, whereas hydroxylation at C-26 was not affected. The common cytochrome P450 inducers, ethanol, MnCl2, phenobarbital, pregnenolone 16α-carbonitrile or clofibrate, did not induce hydroxylation activity at C-25 or at C-26. In addition, substrate analogues (22S,23S-homobrassinolide, 24-epi-castasterone, ecdysone, and 20-OH-ecdysone) were not accepted. Only application of 24-epi-brassinolide and brassinolide resulted in an increased activity of both the C-25- and C-26-hydroxylases. For further examination of the molecular level of this inducing effect, the influence of the protein biosynthesis inhibitor cycloheximide has been studied. Thus, increase of both hydroxylase activities is obviously based on gene expression by action of the substrates, 24-epi-brassinolide and brassinolide.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2421
TI  - The Chromium Reformatsky Reaction: Acces to Adjacent Quarternary Centers
JO  - Synthesis
PY  - 1997
SP  - 512-514
AU  - Wessjohann, L.
AU  - Wild, H.
AU  - 
VL  - 1997
UR  - 
DO  - 10.1055/s-1997-1219
AB  - α-Bromo ketones, -esters and -nitriles react with chromium dichloride and ketones in a Barbier-type reaction to yield the kinetic crossed aldol products with one or two new quarternary centers. The reaction does not require special activation of the reagent, proceeds at room temperature and is suitable for microscale preparations. Crotonates react highly regioselective to yield α-products. The influence of solvents is discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2420
TI  - Excellent Aldehyde and Ketone Selectivity in Chromium(II)-Mediated Reformatsky Reactions
JO  - Synlett
PY  - 1997
SP  - 731-733
AU  - Wessjohann, L.
AU  - Wild, H.
AU  - 
VL  - 1997
UR  - 
DO  - 10.1055/s-1997-3239
AB  - The chromium Reformatsky reaction allows the highly chemoselective addition of ester enolates to aldehydes or methyl ketones at room temperature. Aldehyde selectivities of ≥ 50:1 vs. methyl ketones and ≥ 200:1 vs. larger ketones and other electrophiles can be achieved in most cases. Methyl ketones are preferred with similar effectivity against higher ketones. Effects of solvents, lithium iodide and substituents are discussed.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2419
TI  - Epothilones: Promising Natural Products with Taxol-Like Activity
JO  - Angew. Chem. Int. Ed.
PY  - 1997
SP  - 715-718
AU  - Wessjohann, L.
AU  - 
VL  - 36
UR  - 
DO  - 10.1002/anie.199707151
AB  - Antitumor agents possibly better than taxol might be drived from the epothilones (depicted on the right), which likewise bind to microtubules. The epothilones, which were discovered by Höfle et al. and Reichenbach et al., are easier to synthesize and more soluble in polar solvents than taxol. The results of in vivo activity studies are now eagerly awaited. The exceptional importance of these new tubulin stabilizers is reflected in the race for synthetic approaches to these compounds that has already led to the first total syntheses and several partial solutions.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2418
TI  - Epothilone: vielversprechende Naturstoffe mit Taxol-ähnlicher Aktivität
JO  - Angew. Chem.
PY  - 1997
SP  - 738-742
AU  - Wessjohann, L.
AU  - 
VL  - 109
UR  - 
DO  - 10.1002/ange.19971090707
AB  - Möglicherweise noch bessere Cytostatica als Taxol sind die von den Arbeitsgruppen Höfle und Reichenbach entdeckten Epothilone (siehe rechts), die ebenfalls an Tubulinaggregate binden. Obendrein sind sie relativ leicht zu synthetisieren und in polaren Lösungsmitteln gut löslich. Mit Spannung werden nun die Ergebnisse aus In‐vitro‐Aktivitätsstudien erwartet. Die außergewöhnliche Bedeutung dieser neuen Tubulinstabilisatoren spiegelt sich in einem Wettlauf um synthetische Zugänge wider, der zu den ersten Totalsynthesen und zahlreichen Teillösungen führte.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2417
TI  - 2-Halo-2-cyclohexenols from 6,6-Dihalobicyclo-[3.1.0]hexanes and Dimethyl Sulfoxide. Studies towards a Non-basic Hydroxide Equivalent.
JO  - Acta Chem. Scand.
PY  - 1997
SP  - 1112-1115
AU  - Wessjohann, L. A.
AU  - Mühlbauer, A.
AU  - Sinks, U.
AU  - 
VL  - 51
UR  - 
DO  - 10.3891/acta.chem.scand.51-1112
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2416
TI  - Tissue-Specific and Development-Dependent Accumulation of Phenylpropanoids in Larch Mycorrhizas
JO  - Plant Physiol.
PY  - 1997
SP  - 15-27
AU  - Weiss, M.
AU  - Mikolajewski, S.
AU  - Peipp, H.
AU  - Schmitt, U.
AU  - Schmidt, J.
AU  - Wray, V.
AU  - Strack, D.
AU  - 
VL  - 114
UR  - 
DO  - 10.1104/pp.114.1.15
AB  - The tissue-specific and development-dependent accumulation of secondary products in roots and mycorrhizas of larch (Larix decidua Mill.; Pinaceae) was studied using high-performance liquid chromatography and histochemical methods. The compounds identified were soluble catechin, epicatechin, quercetin 3-O-[alpha]-rhamnoside, cyanidin- and peonidin 3-O-[beta]-glucoside, 4-O-[beta]-hydroxybenzoyl-O-[beta]-glucose, 4-hydroxybenzoate 4-O-[beta]-glucoside, maltol 3-O-[beta]-glucoside, and the wall-bound 4-hydroxybenzaldehyde, vanillin, and ferulate. In addition, we partially identified a tetrahydroxystilbene monoglycoside, a quercetin glycoside, and eight oligomeric proanthocyanidins. Comparison between the compounds accumulating in the apical tissue of fine roots, long roots, and in vitro grown mycorrhizas (L. decidua-Suillus tridentinus) showed elevated levels of the major compounds catechin and epicatechin as well as the minor compound 4-hydroxybenzoate 4-O-[beta]-glucoside specifically in the root apex of young mycorrhizas. The amounts of wall-bound 4-hydroxybenzaldehyde and vanillin were increased in all of the mycorrhizal sections examined. During the early stages of mycorrhization the concentrations of these compounds increased rapidly, perhaps induced by the mycorrhizal fungus. In addition, studies of L. decidua-Boletinus cavipes mycorrhizas from a natural stand showed that the central part of the subapical cortex tissue and the endodermis both accumulate massive concentrations of catechin, epicatechin, and wall-bound ferulate compared with the outer part of the cortex, where the Hartig net is being formed.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2413
TI  - Synthesis of 24-epicathasterone and related brassinosteroids with modified side chain
JO  - Tetrahedron
PY  - 1997
SP  - 17039-17054
AU  - Voigt, B.
AU  - Porzel, A.
AU  - Bruhn, C.
AU  - Wagner, C.
AU  - Merzweiler, K.
AU  - Adam, G.
AU  - 
VL  - 53
UR  - 
DO  - 10.1016/S0040-4020(97)10146-6
AB  - The synthesis of 24-epicathasterone (20), 22-deoxy-24-epiteasterone (22) and 24-hydroxy-6-oxo-24-epicampestanol (24) via 22,23-epoxy- and 22,23-bromohydrin intermediates starting with ergosterol is reported. The structures of the new brassinosteroids were determined especially by X-ray analysis of intennediate bromohydrins.The synthesis of 24-epicathasterone, 22-deoxy-24-epiteasterone and 24-hydroxy-6-oxo-24-epicampestanol via 22,23-epoxy- and 22,23-bromohydrin intermediates starting with ergosterol is reported. The structures of the new brassinosteroids were determined especially by X-ray analysis of intermediate bromohydrins.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2411
TI  - Side Chain Conformation of the Growth-Promoting Phytohormones Brassinolide and 24-Epibrassinolide
JO  - Magn. Reson. Chem.
PY  - 1997
SP  - 629-636
AU  - Stoldt, M.
AU  - Porzel, A.
AU  - Adam, G.
AU  - Brandt, W.
AU  - 
VL  - 35
UR  - 
DO  - 10.1002/(SICI)1097-458X(199709)35:9&lt;629::AID-OMR147&gt;3.0.CO;2-E
AB  - Quantitative 2D NOE measurements and restrained molecular dynamics simulations (with explicit solvent) were carried out in order to determine preferential solution side chain conformations of the two most important native brassinosteroids, brassinolide and 24‐epibrassinolide. The NOE assignment was assisted by 1D NOE difference spectroscopy and included prochiral assignment of the side chain methyl groups Me‐26 and Me‐27. 2D NOE intensities were converted into inter‐proton distances using the ‘complete relaxation matrix analysis’ methodology. Restrained molecular dynamics simulations in a chloroform solvent box led to a well defined solution conformation in the case of brassinolide. The increased side chain flexibility in the case of 24‐epibrassinolide is discussed, considering missing NOE correlations and vicinal proton coupling constants.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2410
TI  - Steroidal alkaloid glycosides from Solanum suaveolens
JO  - Phytochemistry
PY  - 1997
SP  - 1279-1282
AU  - Ripperger, H.
AU  - Porzel, A.
AU  - 
VL  - 46
UR  - 
DO  - 10.1016/S0031-9422(97)80027-1
AB  - In addition to khasianine, solamargine, xylosylsolamargine and solasonine, three steroidal alkaloid glycosides, solasuaveoline, dihydrosolasuaveoline and isosolasuaveoline, have been isolated from aerial parts of Solanum suaveolens. The structures have been assigned by NMR investigations as (25R)-3β-{O-β-d-glucopyranosyl-(1 → 2)-O-β-d-glucopyranosyl-(1 → 4)-[O-α-l-rhamnopyranosyl-(1 → 2)]-β-d-galactopyranosyloxy}-22αN-spirosol-5-ene, (25R)-3β-{O-β-d-glucopyranosyl-(1 → 2)-O-β-d-glucopyranosyl-(1 → 4)-[O-α-l-rhamnopyranosyl-(1 → 2)]-β-d-galactopyranosyloxy}-5α,22αN-spirosolane and (25R)-3β-{O-β-d-glucopyranosyl-(1 → 6)-O-β-d-glucopyranosyl-(1 → 3)-[O-α-l-rhamnopyranosyl-(1 → 2)]-β-d-galactopyranosyloxy}-22αN-spirosol-5-ene, respectively.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2409
TI  - 21′-di-dehydro-deacetyllanatoside C, a biotransformation product of deacetyllanatoside C from senescent shoot cultures of Digitalis lanata
JO  - Phytochemistry
PY  - 1997
SP  - 1061-1064
AU  - Rhenius, M.
AU  - Porzel, A.
AU  - Diettrich, B.
AU  - Luckner, M.
AU  - 
VL  - 44
UR  - 
DO  - 10.1016/S0031-9422(96)00676-0
AB  - Feeding deacetyllanatoside C to senescent shoot cultures of Digitalis lanata resulted in the formation of a new product, which was isolated by semi-preparative HPLC. The molecular structure was elucidated by means of HPLC-mass spectrometry and NMR as 21′-di-dehydro-deacetyllanatoside C.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2408
TI  - Arbuscular mycorrhizal fungus-induced changes in the accumulation of secondary compounds in barley roots
JO  - Phytochemistry
PY  - 1997
SP  - 581-587
AU  - Peipp, H.
AU  - Maier, W.
AU  - Schmidt, J.
AU  - Wray, V.
AU  - Strack, D.
AU  - 
VL  - 44
UR  - 
DO  - 10.1016/S0031-9422(96)00561-4
AB  - Hordeum vulgare (barley) was grown in a defined nutritional medium with and without the arbuscular mycorrhizal fungus Glomus intraradices. HPLC of methanolic extracts from the roots of mycorrhized and non-mycorrhized plants revealed fungus-induced accumulation of some secondary metabolites. These compounds were isolated and identified by spectroscopic methods (NMR, MS) to be the hydroxycinnamic acid amides N-(E)-4-coumaroylputrescine, N-(E)-feruloylputrescine, N-(E)-4-coumaroylagmatine and N-(E)-feruloylagmatine, exhibiting a transient accumulation, and the cyclohexenone derivatives 4-(3-O-β-glucopyranosyl-butyl)-3-(hydroxymethyl)-5,5-dimethyl-2-cyclohexen-1-one and 4-{3-O-[(2′-O-β-glucuronosyl)-β-glucopyranosyl]-butyl}-3,5,5-trimethyl-2-cyclohexen-1-one (blumenin), exhibiting a continuous accumulation. A third cyclohexenone derivative, 4-{3-O-[(2′-O-β-glucuronosyl)-β-glucopyranosyl]-1-butenyl}-3,5,5-trimethyl-2-cyclohexen-1-one, was detectable only in minute amounts. It is suggested that accumulation of the amides in early developmental stages of barley mycorrhization reflects initiation of a defence response. However, the continuous accumulation of the cyclohexenone derivatives, especially blumenin, seems to correlate with the establishment of a functional barley mycorrhiza.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2407
TI  - Synthesis of Tripeptide Fragments of 14-Membered Cyclopeptide Alkaloids
JO  - J. Prakt. Chem.
PY  - 1997
SP  - 467-472
AU  - Mostardeiro, M. A.
AU  - Ethur, E. M.
AU  - Morel, A. F.
AU  - Wessjohann, L. A.
AU  - 
VL  - 339
UR  - 
DO  - 10.1002/prac.19973390183
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2404
TI  - Methyljasmonate-induced accumulation of coumaroyl conjugates in barley leaf segments
JO  - Phytochemistry
PY  - 1997
SP  - 589-592
AU  - Lee, J.
AU  - Vogt, T.
AU  - Schmidt, J.
AU  - Parthier, B.
AU  - Löbler, M.
AU  - 
VL  - 44
UR  - 
DO  - 10.1016/S0031-9422(96)00562-6
AB  - The effect of methyljasmonate on the induction of phenolic components in barley leaf segments was investigated. RP-HPLC of methanol extracts showed that three compounds accumulate to high concentrations in response to methyljasmonate treatment. Two of them were identified as N-(E)-4-coumaroylputrescine and N-(E)-4-coumaroylagmatine by UV-spectroscopy and mass spectrometry.
A2  - 
C1  - Bioorganic Chemistry; Cell and Metabolic Biology
ER  - 


TY  - JOUR
ID  - 2400
TI  - Diglycosidic metabolites of 24-epi-teasterone in cell suspension cultures of Lycopersicon esculentum L.
JO  - Phytochemistry
PY  - 1997
SP  - 1019-1022
AU  - Kolbe, A.
AU  - Porzel, A.
AU  - Schneider, B.
AU  - Adam, G.
AU  - 
VL  - 46
UR  - 
DO  - 10.1016/S0031-9422(97)00390-7
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2398
TI  - Opioid-Agonisten und -Antagonisten, Opioid-Rezeptoren
JO  - Pharmazie
PY  - 1997
SP  - 4-22
AU  - Holzgrabe, U.
AU  - Nachtsheim, C.
AU  - Siener, T.
AU  - Drosihn, S.
AU  - Brandt, W.
AU  - 
VL  - 52
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2392
TI  - The chromium—Reformatsky reaction: Asymmetric synthesis of the aldol fragment of the cytotoxic epothilons from 3-(2-bromoacyl)-2-oxazolidinones
JO  - Tetrahedron Lett.
PY  - 1997
SP  - 1363-1366
AU  - Gabriel, T.
AU  - Wessjohann, L.
AU  - 
VL  - 38
UR  - 
DO  - 10.1016/S0040-4039(96)02494-X
AB  - In a two step, one pot reaction of 4-benzyl oxazolidinone, 2-bromoacetyl halide, chromium dichloride and a suitable 3-oxo-aldehyde derivative the C1C6Me - fragment of epothilons is available in its correct oxidation state and enantiomeric form. Compared to common methods, the chromium-Reformatsky variation preferentially yields the opposite diastereomers and gives improved chemo- and diastereoselection.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2391
TI  - The chromium-Reformatsky reaction: anti-selective Evans-type aldol reactions with excellent inverse induction at ambient temperature
JO  - Tetrahedron Lett.
PY  - 1997
SP  - 4387-4388
AU  - Gabriel, T.
AU  - Wessjohann, L.
AU  - 
VL  - 38
UR  - 
DO  - 10.1016/S0040-4039(97)00952-0
AB  - anti-Aldol products are available in a two step, one pot reaction of 4-substituted oxazolidone, 2-bromopropionyl halide, chromium dichloride and an aldehyde. The diastereofacial selection (induction) is opposite to those of boron Evans enolates, i. e. the unusual “non-Evans” anto-aldol products are formed in excellent excess and yield - without base and at room temperature. In contrast to our previous assumptions α-unsubstituted acetyloxazolidones do give the Evans-type β-anti-products preferentially.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2390
TI  - Partial Synthesis of [1β,2α,17,17-D4] Gibberellin A1
JO  - J. Prakt. Chem.
PY  - 1997
SP  - 448-452
AU  - Fuchs, P.
AU  - Porzel, A.
AU  - Schneider, G.
AU  - 
VL  - 339
UR  - 
DO  - 10.1002/prac.19973390178
AB  - An efficient route for an alternative synthesis of gibberllin A1 from gibberellin A3 is described. Based on iodolactonisation the method provides access to gibberellin A1 labeled by deuterium with both high incorporation of the isotope and high stereoselectity at the positions 1β and 2α. The additional deuterium labeling at C‐17 was introduced via  the corresponding 16‐norketone resulting in [1β,2α,17,17‐D4] gibberellin A1.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2389
TI  - Structural Elucidation of Oxygenated Storage Lipids in Cucumber Cotyledons
JO  - J. Biol. Chem.
PY  - 1997
SP  - 21635-21641
AU  - Feussner, I.
AU  - Balkenhohl, T. J.
AU  - Porzel, A.
AU  - Kühn, H.
AU  - Wasternack, C.
AU  - 
VL  - 272
UR  - 
DO  - 10.1074/jbc.272.34.21635
AB  - At early stages of germination, a special lipoxygenase is expressed in cotyledons of cucumber and several other plants. This enzyme is localized at the lipid storage organelles and oxygenates their storage triacylglycerols. We have isolated this lipid body lipoxygenase from cucumber seedlings and found that it is capable of oxygenating in vitro di- and trilinolein to the corresponding mono-, di-, and trihydroperoxy derivatives. To investigate the in vivo activity of this enzyme during germination, lipid bodies were isolated from cucumber seedlings at different stages of germination, and the triacylglycerols were analyzed for oxygenated derivatives by a combination of high pressure liquid chromatography, gas chromatography/mass spectrometry, and nuclear magnetic resonance spectroscopy. We identified as major oxygenation products triacylglycerols that contained one, two, or three 13S-hydroperoxy-9(Z),11(E)-octadecadienoic acid residues. During germination, the amount of oxygenated lipids increased strongly, reaching a maximum after 72 h and declining afterward. The highly specific pattern of hydroperoxy lipids formed suggested the involvement of the lipid body lipoxygenase in their biosynthesis.These data suggest that this lipoxygenase may play an important role during the germination process of cucumber and other plants and support our previous hypothesis that the specific oxygenation of the storage lipids may initiate their mobilization as a carbon and energy source for the growing seedling.
A2  - 
C1  - Molecular Signal Processing; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2388
TI  - Quantitative Analyse von Lipoxygenase-Metaboliten in Lipiden durch NMR-Spektroskopie
JO  - BIOspektrum
PY  - 1997
SP  - 54-58
AU  - Feussner, I.
AU  - Porzel, A.
AU  - Wasternack, C.
AU  - Kühn, H.
AU  - 
VL  - 3
UR  - 
AB  - 
A2  - 
C1  - Molecular Signal Processing; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2384
TI  - Benzopyranones and ferulic acid derivatives from Antidesma membranaceum
JO  - Phytochemistry
PY  - 1997
SP  - 1385-1388
AU  - Buske, A.
AU  - Schmidt, J.
AU  - Porzel, A.
AU  - Adam, G.
AU  - 
VL  - 46
UR  - 
DO  - 10.1016/S0031-9422(97)00488-3
AB  - From Antidesma membrananeum, besides three feruloyl amides and (−)-syringaresinol, new phenolic compounds have been isolated. Their structures were established as two series of 2-alkylated 5,7-dihydroxychromones and 2,5,7-trihydroxychromanones, and the dimeric compound, 8,8-bis-(dihydroconiferyl)-diferuloylate, respectively, from their spectroscopic data.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2383
TI  - Determination of Configuration at the Biaryl Axes of Naphthylisoquinoline Alkaloids by Long-Range NOE Effects
JO  - Magn. Reson. Chem.
PY  - 1997
SP  - 297-301
AU  - Bringmann, G.
AU  - Koppler, D.
AU  - Scheutzow, D.
AU  - Porzel, A.
AU  - 
VL  - 35
UR  - 
DO  - 10.1002/(SICI)1097-458X(199705)35:5&lt;297::AID-OMR88&gt;3.0.CO;2-J
AB  - One‐ and two‐dimensional NOE and ROE experiments were applied to investigate the relative configuration at the stereogenic biaryl axes of naphthylisoquinoline alkaloids, natural biaryl compounds mainly occurring as stable atropisomers. The influence of ortho  substitution at the biaryl axes on the dynamic behavior of the atropo‐diastereomers and the determined NOE effects was investigated. As an example, the axial configuration of ancistrobrevine A was elucidated by the method.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2382
TI  - Triterpenoids from Pisolithus tinctorius isolates and ectomycorrhizas
JO  - Phytochemistry
PY  - 1997
SP  - 499-504
AU  - Baumert, A.
AU  - Schumann, B.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Strack, D.
AU  - 
VL  - 45
UR  - 
DO  - 10.1016/S0031-9422(97)00007-1
AB  - Two new triterpenoids have been identified by spectroscopic methods from mycelia of Pisolithus tinctorius as 24-ethyllanosta-8,24(241)-diene-3β,22ξ-diol and (22S)-24,25-dimethyllanosta-8-en-22,241-epoxy-3β-ol-241-one (25-methylpisolactone) along with the two known triterpenoids 24-methyllanosta-8,24(241)-diene-3β,22ξ-diol and (22S)-24-methyllanosta-8-en-22,241-epoxy-3β-ol-241-one (pisolactone). Quantification of these compounds in fungal isolates (surface and suspension cultures) and Pinus sylvestris ectomycorrhizas showed that the amount of the new triterpenoids was markedly higher in the mycorrhizas as in the isolates.
A2  - 
C1  - Cell and Metabolic Biology; Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2381
TI  - Tetralones from Ancistrocladus cochinchinensis
JO  - Phytochemistry
PY  - 1997
SP  - 549-551
AU  - Anh, N. H.
AU  - Ripperger, H.
AU  - Porzel, A.
AU  - Sung, T. V.
AU  - Adam, G.
AU  - 
VL  - 44
UR  - 
DO  - 10.1016/S0031-9422(96)00510-9
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2380
TI  - Neolignans from Caryodaphnopsis baviensis
JO  - Phytochemistry
PY  - 1997
SP  - 569-571
AU  - Anh, N. H.
AU  - Ripperger, H.
AU  - Porzel, A.
AU  - Sung, T. V.
AU  - Adam, G.
AU  - 
VL  - 46
UR  - 
DO  - 10.1016/S0031-9422(97)00209-4
AB  - Besides the eupomatenoids 1, 3, 5 and 6, 5-(erythro-1,2-dihydroxypropyl)-2-(4-hydroxyphenyl)-3-methylbenzo[b]furan, 5-(erythro-1,2-dihydroxypropyl)-2-(4-hydroxy-3-methoxyphenyl)-3-methylbenzo[b]furan, (2R,3R)-2,3-dihydro-2-(4-hydroxyphenyl)-3-methyl-5-[(E)-1-propenyl]benzo[b]furan, erythro-1-(3,4-methylenedioxyphenyl)-2-{4-[(E)-1-propenyl]phenoxy}propan-1-ol, (+)-sesamin, isolinderanolide and icariside D1, two new neolignans have been isolated from Caryodaphnopsis baviensis. Their structures were elucidated as 3-methyl-2-(3,4-methylenedioxyphenyl)-5-[(E)-3-oxo-1-propenyl]benzo[b]furan and 4-hydroxy-α-{4-[(E)-1-propenyl]phenoxy}propiophenone.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2379
TI  - Naphthylisoquinoline alkaloids from Ancistrocladus cochinchinensis
JO  - Phytochemistry
PY  - 1997
SP  - 1287-1291
AU  - Anh, N. H.
AU  - Porzel, A.
AU  - Ripperger, H.
AU  - Bringmann, G.
AU  - Schäffer, M.
AU  - God, R.
AU  - Van Sung, T.
AU  - Adam, G.
AU  - 
VL  - 45
UR  - 
DO  - 10.1016/S0031-9422(97)00110-6
AB  - From the leaves of Ancistrocladus cochinchinensis, besides the already known ancistrocladinine, the new naturally occurring alkaloids, 6-O-methylhamateine, hamatinine, 6-O-methylhamatinine, 6-O-demethyl-7-epi-ancistrobrevine D, 7-epi- ancistrobrevine D and 6-O-demethyl-8-O-methyl-7-epi-ancistrobrevine D have been isolated and their structures elucidated from spectroscopic data and chemical degradation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 183
TI  - The Development of Aromatic Prenylation for Organic Synthesis
T2  - 6. Nachwuchswissenschaftler-Symposium Bioorganische Chemie - Book of Abstracts
PB  - 
PY  - 1997
SP  - 
AU  - Sontag, B.
AU  - Scheid, G.
AU  - Straudi, A.
AU  - Wessjohann, L. A.
AU  - 
VL  - 
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 182
TI  - Triterpene
T2  - RÖMPP-Lexikon Naturstoffe
PB  - 
PY  - 1997
SP  - 
AU  - Schmidt, J.
AU  - 
VL  - 
UR  - 
AB  - 
A2  - Steglich, W., Fugmann,B., Lang-Fugmann, S.
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 180
TI  - A Molecular Model of the Active Site of Dipeptidyl Peptidase IV
T2  - Cellular Peptidases in Immune Functions and Diseases
PB  - Adv. Exp. Med. Biol.
PY  - 1997
SP  - 171-178
AU  - Brandt, W.
AU  - 
VL  - 421
UR  - 
DO  - 10.1007/978-1-4757-9613-1_22
AB  - The ectoenzyme dipeptidyl peptidase IV (DPP IV) is an integral plasma membrane glycoprotein abundantly expressed on a variety of cell surfaces.1 It is a serine peptidase of broad medical and biochemical significance. It plays a role in the degradations and post translational processing of bioactive peptides such as substance P, ß-casomorphins, growth hormone-releasing hormone and promelittin.2–9 DPP IV has been identified as CD26.10 Recently, it could be demonstrated that it is not only a surface differentiation marker involved in the transduction of mitogenic signals in thymocytes and T lymphocytes in human but also a cofactor in AIDS expression.10–13
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2449
TI  - Prenylierung von Benzoesäurederivaten, katalysiert durch eine Transferase aus Escherichia-coli-Überproduzenten: Verfahrensentwicklung und Substratspezifität
JO  - Angew. Chem.
PY  - 1996
SP  - 1821-1823
AU  - Wessjohann, L.
AU  - Sontag, B.
AU  - 
VL  - 108
UR  - 
DO  - 10.1002/ange.19961081527
AB  - Die enzymatische Friedel‐Crafts‐Alkylierung zur Synthese bis zu fünffach kernsubstituierter 3‐Polyprenylbenzoesäurederivate gelingt regiospezifisch mit einer Polyprenyl‐Transferase, die ein erstaunlich breites Substratspektrum aufweist [Gl. (a); PP = Pyrophosphat]. Obwohl es sich um ein Membranenzym handelt, sind wegen der einfachen Gewinnung und Anreicherung sowie der guten Lagerstabilität die Voraussetzungen für den Einsatz in der organischen Synthese ausgezeichnet.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2448
TI  - Prenylation of Benzoic Acid Derivatives Catalyzed by a Transferase from Escherichia coli Overproduction: Method Development and Substrate Specificity
JO  - Angew. Chem. Int. Ed.
PY  - 1996
SP  - 1697-1699
AU  - Wessjohann, L.
AU  - Sontag, B.
AU  - 
VL  - 35
UR  - 
DO  - 10.1002/anie.199616971
AB  - The enzymatic Friedel–Crafts alkylation for the synthesis of up to fivefold ring‐substituted 3‐polyprenylbenzoic acid derivatives can be accomplished regiospecifically with a polyprenyl‐transferase, which exhibits a surprisingly broad substrate spectrum ([Eq. (a)]; OPP = pyrophosphate). Although a membrane enzyme, its simple production and enrichment, and good shelf life provide an excellent basis for general use in organic synthesis.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2447
TI  - Dispositivo de Segurança de Baixo Custo e de Fácil Montagem para Controle de Circuitos Elétricos Acoplados a Fluxo d&#39;água
JO  - Quím. Nova
PY  - 1996
SP  - 554-555
AU  - Wessjohann, L. A.
AU  - Zanatta, N.
AU  - 
VL  - 19
UR  - http://quimicanova.sbq.org.br/detalhe_artigo.asp?id=4129
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 187
TI  - New brassinosteroids from Ornithopus sativus and Apium graveolens
T2  - Applications of Modern Mass Spectrometry in Plant Science Research
PB  - 
PY  - 1996
SP  - 229-233
AU  - Schmidt, J.
AU  - Spengler, B.
AU  - Voigt, B.
AU  - Adam, G.
AU  - 
VL  - 
UR  - 
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 186
TI  - Aldol Reactions Made Irreversible by an Intrinsic Kinetic Quench: The Chromium Reformatsky Reaction
T2  - 11th International Conference On Organic Synthesis (ICOS-11), KNCV and IUPAC
PB  - 
PY  - 1996
SP  - 317
AU  - Gabriel, T.
AU  - Wessjohann, L.
AU  - 
VL  - 
UR  - 
AB  - 
A2  - Hiemstra, H., ed.
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2467
TI  - The pinene path to taxol: Readily accessible a-ring building blocks based on novel alkyl- and alkenyllithium reagents with internal carbonyl groups
JO  - Tetrahedron Lett.
PY  - 1995
SP  - 7181-7184
AU  - Wender, P. A.
AU  - Wessjohann, L. A.
AU  - Peschke, B.
AU  - Rawlins, D. B.
AU  - 
VL  - 36
UR  - 
DO  - 10.1016/0040-4039(95)01491-Y
AB  - The synthesis and chemistry of the novel reagents and stereochemically defined taxane A-ring building blocks 7e–9e are described, providing the basis for the solution to problems previously encountered in the development of syntheses of taxol and its analogs based on pinene.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2463
TI  - Cyclopeptide alkaloids of Discaria febrifuga (Rhamnaceae)
JO  - Phytochemistry
PY  - 1995
SP  - 431-434
AU  - Morel, A. F.
AU  - Machado, E. C.
AU  - Wessjohann, L. A.
AU  - 
VL  - 39
UR  - 
DO  - 10.1016/0031-9422(94)00924-I
AB  - From the methanol extract of the root bark of Discaria febrifuga Mart., in addition to the already described alkaloid, a new peptide alkaloid discarine-L has been isolated and its structure elucidated. This alkaloid differs from most of the known 14-membered peptide alkaloids by a 2-hydroxy-2-phenethylamine residue.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2459
TI  - Occurrence and identification of jasmonic acid and its amino acid conjugates induced by osmotic stress in barley leaf tissue
JO  - J. Plant Growth Regul.
PY  - 1995
SP  - 29-36
AU  - Kramell, R.
AU  - Atzorn, R.
AU  - Schneider, G.
AU  - Miersch, O.
AU  - Brückner, C.
AU  - Schmidt, J.
AU  - Sembdner, G.
AU  - Parthier, B.
AU  - 
VL  - 14
UR  - 
DO  - 10.1007/BF00212643
AB  - The effect of osmotically active substances on the alteration of endogenous jasmonates was studied in barley (Hordeum vulgare L. cv. Salome) leaf tissue. Leaf segments were subjected to solutions of d-sorbitol, d-mannitol, polyethylene glycol 6000, sodium chloride, or water as a control. Alterations of endogenous jasmonates were monitored qualitatively and quantitatively using immunoassays. The structures of jasmonates isolated were determined on the basis of authentic substances by capillary gas chromatography-mass spectrometry. The stereochemistry of the conjugates was confirmed by high performance liquid chromatography with diastereoisomeric references. In barley leaves, jasmonic acid and its amino acid conjugates, for example, with valine, leucine, and isoleucine, are naturally occurring jasmonates. In untreated leaf segments, only low levels of these native jasmonates were found. After treatment of the leaf tissues with sorbitol, mannitol, as well as with polyethylene glycol, an increase of both jasmonic acid and its conjugates could be observed, depending on the stress conditions used. In contrast, salt stress was without any stimulating effect on the levels of endogenous jasmonates. From barley leaf segments exposed to sorbitol (1m) for 24 h, jasmonic acid was identified as the major accumulating compound. Jasmonic acid-amino acid conjugates increased likewise upon stress treatment.
A2  - 
C1  - Bioorganic Chemistry; Molecular Signal Processing
ER  - 


TY  - JOUR
ID  - 2453
TI  - Catalyst-Dependent Selective Synthesis of O/S- and S/S-Acetals from Enol Ethers
JO  - Synth. Commun.
PY  - 1995
SP  - 3155-3162
AU  - Braga, A. L.
AU  - Silveira, C. C.
AU  - Dornelles, L.
AU  - Zeni, G.
AU  - Galarza, F. A. D.
AU  - Wessjohann, L. A.
AU  - 
VL  - 25
UR  - 
DO  - 10.1080/00397919508015466
AB  - Enol ethers are reacted with mercaptanes to give the corresponding O/S- or S/S-acetals in medium to high yield. Either product can be formed selectively depending on the acid catalyst and the reaction time applied.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 189
TI  - The Pinene Path to Taxanes
T2  - Taxane Anticancer Agents
PB  - ACS Sym. Ser.
PY  - 1995
SP  - 326-339
AU  - Wender, P. A.
AU  - Badham, N. F.
AU  - Conway, S. P.
AU  - Floreancig, P. E.
AU  - Glass, T. E.
AU  - Houze, J. B.
AU  - Krauss, N. E.
AU  - Lee, D.
AU  - Marquess, D. G.
AU  - McGrane, P. L.
AU  - Meng, W.
AU  - Mucciaro, T. P.
AU  - Mühlebach, M.
AU  - Natchus, M. G.
AU  - Ohkuma, T.
AU  - Peschke, B.
AU  - Rawlins, D. B.
AU  - Shuker, A. J.
AU  - Sutton, J. C.
AU  - Taylor, R. E.
AU  - Tomooka, K.
AU  - Wessjohann, L. A.
AU  - 
VL  - 583
UR  - 
SN  - 9780841215078
DO  - 10.1021/bk-1995-0583.ch024
AB  - Taxol is a recent and striking example of the continuing impact of natural products chemistry on science and human health and a reminder of the significant return that is realized through investment in basic research. First isolated in the sixties from the bark of the Pacific Yew by chemists Wall, Wani, and their colleagues working in collaboration with the National Cancer Institute (1), taxol was found to possess a novel polycyclic structure (1) punctuated by a central eight-membered ring. Interest in the chemotherapeutic potential of this compound was stimulated by early cytotoxicity studies and greatly amplified by the subsequent proposal by Horwitz and coworkers that taxol operates through a new molecular mode of action involving the facilitated assembly and stabilization of microtubules (2). Clinical trials of taxol in the eighties proved to be sufficiently promising to warrant its subsequent approval for use in the treatment of ovarian cancer and, more
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 188
TI  - New Developments in Brassinosteroid Research
T2  - Stereoselective Synthesis (Part K)
PB  - Stud. Nat. Prod. Chem.
PY  - 1995
SP  - 495-549
AU  - Adam, G.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Schneider, B.
AU  - Voigt, B.
AU  - 
VL  - 18
UR  - 
DO  - 10.1016/S1572-5995(96)80033-0
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2477
TI  - The First Total Syntheses of Taxol
JO  - Angew. Chem. Int. Ed.
PY  - 1994
SP  - 959-961
AU  - Wessjohann, L.
AU  - 
VL  - 33
UR  - 
DO  - 10.1002/anie.199409591
AB  - A milestone in natural product chemistry is the first total synthesis of taxol achieved independently of each other by the groups of R. A. Holton and K. C. Nicolaou. Taxol is at present the most promising anti‐cancer agent, and its synthesis is extremely demanding. It is highly unlikely that this climax will be the end of probably the greatest worldwide effort yet to synthesize a single compound.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2476
TI  - Die ersten Totalsynthesen von Taxol
JO  - Angew. Chem.
PY  - 1994
SP  - 1011-1013
AU  - Wessjohann, L.
AU  - 
VL  - 106
UR  - 
DO  - 10.1002/ange.19941060906
AB  - Ein Meilenstein der Naturstoffchemie ist die Totalsynthese des zur Zeit vielversprechendsten und synthetisch extrem anspruchsvollen Antikrebsmittels Taxol, die unabhängig voneinander den Arbeitsgruppen von R.A. Holton und K.C. Nicolaou gelang. Mit diesem vorläufigen Höhepunkt dürfte der vermutlich weltweit größte Aufwand zur Totalsynthese einer Einzelverbindung jedoch nicht beendet sein.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2470
TI  - Acridone Alkaloids from Cell Suspension Cultures of Thamnosma montana
JO  - Planta Med.
PY  - 1994
SP  - 143-145
AU  - Baumert, A.
AU  - Maier, W.
AU  - Matern, U.
AU  - Schmidt, J.
AU  - Schumann, B.
AU  - Gröger, D.
AU  - 
VL  - 60
UR  - 
DO  - 10.1055/s-2006-959437
AB  - Cell Suspension cultures of Thamnosma montana were grown in Gamborg B5 medium which was best suited for acridone alkaloid formation. From the lyophilized cell material nine acridones and three acridone-monoglucosides have been isolated which were found for the first time in the genus Thamnosma. Moreover, N-methylacridone which is known from the intact plant was found. Gravacridonol monoglucoside was identified as a new alkaloid. Interestingly, most isolated alkaloids belong to the dihydrofuroacridones.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2483
TI  - Facile synthesis of stable analogs of 2-oxocyclobutanecarboxylates: 2-[(diphenylmethylene)amino]cyclobutenecarboxylates, derivatives and reactions
JO  - J. Org. Chem.
PY  - 1993
SP  - 6442-6450
AU  - Wessjohann, L.
AU  - Giller, K.
AU  - Zuck, B.
AU  - Skattebøl, L.
AU  - de Meijere, A.
AU  - 
VL  - 58
UR  - 
DO  - 10.1021/jo00075a047
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2479
TI  - Synthesis of the Bioactive Tripeptide Bursin By Classical Methods
JO  - J. Braz. Chem. Soc.
PY  - 1993
SP  - 147-149
AU  - Dalcol, I. I.
AU  - Braibante, H. S. T.
AU  - Zanatta, N.
AU  - Morel, A. F.
AU  - Wessjohann, L. A.
AU  - 
VL  - 4
UR  - 
DO  - 10.5935/0103-5053.19930032
AB  - 
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2478
TI  - Synthesis and mass spectral analysis of coenzyme a thioesters of anthranilic acid and its N-methyl derivative involved in acridone alkaloid biosynthesis
JO  - Phytochem. Anal.
PY  - 1993
SP  - 165-170
AU  - Baumert, A.
AU  - Schmidt, J.
AU  - Gröger, D.
AU  - 
VL  - 4
UR  - 
DO  - 10.1002/pca.2800040406
AB  - Coenzyme A thioesters of anthranilic acid and N‐methylanthranilic acid were synthesized. The corresponding N‐hydroxysuccinimidyl esters proved to be useful as activated intermediates to prepare anthraniloyl‐CoA and N‐methylanthraniloyl‐CoA. These compounds were characterized by positive and negative ion liquid secondary ion mass spectrometry. Acridone synthase from suspension cultures of Ruta graveolens  catalyses the condensation of N‐methylanthraniloyl‐CoA and malonyl‐CoA. The reaction product 1,3‐dihydroxy‐N‐methylacridone was directly identified after the extraction of the assay mixture by electron impact mass spectrometry and capillary gas chromatography.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2486
TI  - A New Versatile Synthesis of Ring-Substituted 2-Cyclopropylglycines and Related Amino Acids
JO  - Chem. Ber.
PY  - 1992
SP  - 867-882
AU  - Wessjohann, L.
AU  - Krass, N.
AU  - Yu, D.
AU  - de Meijere, A.
AU  - 
VL  - 125
UR  - 
DO  - 10.1002/cber.19921250418
AB  - Alkyl 2‐chloro‐2‐cyclopropylideneacetates 2  serve as universal starting materials for a new general synthesis of cyclopro‐pylglycines by a simple three‐ to four‐step methodology. 1,4‐Addition of nucleophiles, substitution with azide ion, and mild catalytic deprotection lead to a variety of salt‐free cyclopropyl‐substituted amino acids in good yields, including the natural products 2‐(1‐methylcyclopropyl)glycine (4 ) and cleonin (5 ).
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2484
TI  - Formation of 1,3-Dihydroxy-N-methylacridone from N-Methylanthraniloyl-CoA and Malonyl-CoA by Cell-Free Extracts of Ruta graveolens
JO  - Z. Naturforsch. C
PY  - 1992
SP  - 365-368
AU  - Baumert, A.
AU  - Porzel, A.
AU  - Schmidt, J.
AU  - Gröger, D.
AU  - 
VL  - 47
UR  - 
DO  - 10.1515/znc-1992-0608
AB  - N-Methylanthraniloyl-CoA was synthesized via N-succinimidyl N-methylanthranilate and subsequent transesterification with CoA-SH . This compound was characterized by LSIMS and NMR data. An enzyme preparation from cell suspension cultures of Ruta graveolens catalyzed the formation of 1,3-dihydroxy-N-methylacridone from N-methylanthraniloyl-CoA and malonyl-CoA with a pH optimum of 7.5.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2489
TI  - New short syntheses of isoquinoline-4-carboxylic acid and 2-aza-3,3a-dihydroazulene-3a-carboxylic acid derivatives
JO  - J. Chem. Soc., Chem. Commun.
PY  - 1990
SP  - 574-576
AU  - Wessjohann, L.
AU  - Skattebøl, L.
AU  - de Meijere, A.
AU  - 
VL  - 1990
UR  - 
DO  - 10.1039/C39900000574
AB  - Cyclopropylideneacetates (2a,b) undergo a formal [2 + 4] cycloaddition with (diphenylmethylene)amine (DPMA-H)(1) to yield dihydro-1-phenylisoquinoline-4-carboxylate (8a) and 1-phenylisoquinoline-4-carboxylate (7b); the Michael adduct of DPMA-H onto (2b), on the other hand, under basic conditions gives 1-phenyl-2-aza-azulene-3a-carboxylate (12) exclusively.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2488
TI  - Tailoring the Reactivity of Small Ring Building Blocks for Organic Synthesis
JO  - Synlett
PY  - 1990
SP  - 20-32
AU  - de Meijere, A.
AU  - Wessjohann, L.
AU  - 
VL  - 1990
UR  - 
DO  - 10.1055/s-1990-20975
AB  - The syntheses and reactivities of some new cyclopropane containing C5-building blocks with composite functionalities are described. Recent applications of cyclopropylideneacetates in short syntheses of spirocyclopropane-annulated heterocycles and cyclopropane-containing biologically active compounds are demonstrated. Cyclopropylacetylenes are employed as cyclopentane annulation reagents and are particularly useful in the construction of terpenoid frameworks. 1. Introduction 2. The Initial Experiment: 1-Chloro-1-(trichlorovinyl)cyclopropanes from Olefins 3. Cyclopropylideneacetates 4. Cyclopropylacetylenes 5. Conclusion
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - JOUR
ID  - 2490
TI  - 1,4-Addition of (Diphenylmethylene)amine to Acceptor Substituted Olefins. A Versatile Synthesis of Protected β-Amino Acids, Nitriles, and Ketones
JO  - Synthesis
PY  - 1989
SP  - 359-363
AU  - Wessjohann, L.
AU  - Mcgaffin, G.
AU  - de Meijere, A.
AU  - 
VL  - 1989
UR  - 
DO  - 10.1055/s-1989-27252
AB  - (Diphenylmethylene)amine [benzophenone imine, DPMA-H] cleanly reacts with a variety of α,β-unsaturated esters, nitriles, ketones, and aldehydes 1a-q to give Michael type adducts 2a-q, generally, in respectable to excellent yields. Sterically congested and donor-substituted Michael acceptors do not react. The β-amino-substituted products can be further transformed in their protected form, or selectively deprotected under mild conditions, e.g. by catalytic hydrogenation.
A2  - 
C1  - Bioorganic Chemistry
ER  - 


TY  - CHAP
ID  - 190
TI  - Cyclopropyl Group Containing Amino Acids From α-Chlorocyclopropylidenacetates
T2  - Strain and Its Implications in Organic Chemistry
PB  - NATO ASI Series
PY  - 1989
SP  - 509-512
AU  - Krass, N.
AU  - Wessjohann, L.
AU  - Yu, D.
AU  - Meijere, A.
AU  - 
VL  - 273
UR  - 
SN  - 978-94-009-0929-8
DO  - 10.1007/978-94-009-0929-8_42
AB  - Cyclopropane amino acids have attracted the attention of synthetically and biologically oriented chemists throughout the last decade. Most efforts have been directed towards 1-aminocyclopropane carboxyclic acid (ACC), the natural precursor of the phytohormone ethylene,1 and its derivatives. Other natural cyclopropane amino acids as well as artificial ones were used as enzyme inhibitors for receptor and metabolism studies.2 We report here a new synthetic approach to a wide variety of cyclopropyl-substituted amino acids including the natural products cleonin (1) (1-hydroxycyclopropyl-glycin)3 and 1-methylcyclopropyl- glycin (2).4
A2  - de Meijere, A. &amp; Blechert, S., eds.
C1  - Bioorganic Chemistry
ER  - 


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