Geschmack ist vorhersagbar: Mit FlavorMiner. FlavorMiner heißt das Tool, das IPB-Chemiker und Partner aus Kolumbien jüngst entwickelt haben. Das Programm kann, basierend auf maschinellem Lernen (KI), anhand der…
Seit Februar 2021 bietet Wolfgang Brandt, ehemaliger Leiter der Arbeitsgruppe Computerchemie am IPB, sein Citizen Science-Projekt zur Pilzbestimmung an. Dafür hat er in regelmäßigen Abständen öffentliche Vorträge zur Vielfalt…
Zhu, M.; Ruijter, E.; Wessjohann, L. A.;New Scavenger Resin for the Reversible Linking and Monoprotection of Functionalized Aromatic AldehydesOrg. Lett.63921-3924(2004)DOI: 10.1021/ol048610h
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.
Publikation
Zakharova, S.; Fulhorst, M.; Luczak, L.; Wessjohann, L.;Synthesis, inhibitory and activation properties of prenyldiphosphate mimics for aromatic prenylations with ubiA-prenyl transferaseARKIVOC200479(2004)DOI: 10.3998/ark.5550190.0005.d10
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.
Publikation
Westermann, B.; Diedrichs, N.; Krelaus, R.; Walter, A.; Gedrath, I.;Diastereoselective synthesis of homologous bicyclic lactams––potential building blocks for peptide mimicsTetrahedron Lett.455983-5986(2004)DOI: 10.1016/j.tetlet.2004.06.051
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.
Publikation
Poeaknapo, C.; Schmidt, J.; Brandsch, M.; Dräger, B.; Zenk, M. H.;Endogenous formation of morphine in human cellsProc. Natl. Acad. Sci. U.S.A.10114091-14096(2004)DOI: 10.1073/pnas.0405430101
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.