jump to searchjump to navigationjump to content

Publications - Bioorganic Chemistry

Sort by: Year Type of publication

Displaying results 1 to 10 of 40.

Publications

Wouters, A. D.; Bessa, A. B.; Sachini, M.; Wessjohann, L. A.; Lüdtke, D. S.; Boron-Zinc Exchange in The Diastereoselective Arylation of Sugar-Based Aldehydes­: Stereoselective Synthesis of (+)-7-epi-Goniofufurone and Analogues Synthesis 45, 2222-2233, (2013) DOI: 10.1055/s-0033-1339285

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.
Publications

Wils, C. R.; Brandt, W.; Manke, K.; Vogt, T.; A single amino acid determines position specificity of an Arabidopsis thaliana CCoAOMT-like O-methyltransferase FEBS Lett. 587, 683-689, (2013) DOI: 10.1016/j.febslet.2013.01.040

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.
Publications

Westermann, B.; Dörner, S.; Brauch, S.; Schaks, A.; Heinke, R.; Stark, S.; van Delft, F. L.; van Berkel, S. S.; CuAAC-mediated diversification of aminoglycoside–arginine conjugate mimics by non-reducing di- and trisaccharides Carbohyd. Res. 371, 61-67, (2013) DOI: 10.1016/j.carres.2013.02.003

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
Publications

Wessjohann, L. A.; Scheid, G. O.; Eichelberger, U.; Umbreen, S.; Total Synthesis of Epothilone D: The Nerol/Macroaldolization Approach J. Org. Chem. 78, 10588-10595, (2013) DOI: 10.1021/jo401355r

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.
Publications

Wessjohann, L. A.; Schneider, A.; Kaluđerović, G. N.; Brandt, W.; Solid-phase synthesis of reduced selenocysteine tetrapeptides and their oxidized analogs containing selenenylsulfide eight-membered rings Mol. Divers. 17, 537-545, (2013) DOI: 10.1007/s11030-013-9454-x

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.
Publications

Wessjohann, L. A.; Keim, J.; Weigel, B.; Dippe, M.; Alkylating enzymes Curr. Opin. Chem. Biol. 17, 229-235, (2013) DOI: 10.1016/j.cbpa.2013.02.016

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.
Publications

Stehle, F.; Götsch, F.; Wray, V.; Schmidt, J.; Strack, D.; Brandt, W.; Snap-shot of Serine Carboxypeptidase-like Acyltransferase Evolution: The Loss of Conserved Disulphide Bridge is Responsible for the Completion of Neo-functionalization J. Phylogenet. Evol. Biol. 1, 115, (2013) DOI: 10.4172/2329-9002.1000115

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.
Publications

Staniek, A.; Bouwmeester, H.; Fraser, P. D.; Kayser, O.; Martens, S.; Tissier, A.; van der Krol, S.; Wessjohann, L.; Warzecha, H.; Natural products - modifying metabolite pathways in plants Biotechnol. J. 8, 1159-1171, (2013) DOI: 10.1002/biot.201300224

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.
Publications

Sproß, J.; Brauch, S.; Mandel, F.; Wagner, M.; Buckenmaier, S.; Westermann, B.; Sinz, A.; Multidimensional nano-HPLC coupled with tandem mass spectrometry for analyzing biotinylated proteins Anal. Bioanal. Chem. 405, 2163-2173, (2013) DOI: 10.1007/s00216-012-6057-9

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.
Publications

Solé, M.; Brandt, W.; Arnold, U.; Striking stabilization of Rana catesbeiana ribonuclease 3 by guanidine hydrochloride FEBS Lett. 587, 737-742, (2013) DOI: 10.1016/j.febslet.2013.01.056

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.
IPB Mainnav Search