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…
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.
Publikation
Milde, R.; Schnabel, A.; Ditfe, T.; Hoehenwarter, W.; Proksch, C.; Westermann, B.; Vogt, T.;Chemical synthesis of trans 8-methyl-6-nonenoyl-CoA and functional expression unravel capsaicin synthase activity encoded by the Pun1 LocusMolecules276878(2022)DOI: 10.3390/molecules27206878
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.
Bücher und Buchkapitel
Ceballos, L. G.; Pacheco, D. F.; Westermann, B.; Garcia-Rivera, D.;Solid-phase heterocycle synthesis using multicomponent reactionsErik Van der Eycken, Upendra K. SharmaMulticomponent Reactions towards Heterocycles: Concepts and Applications4139-162(2022)ISBN:9783527349081DOI: 10.1002/9783527832439.ch4
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.
Publikation
Ali, A.; Corrêa, A. G.; Alves, D.; Zukerman-Schpector, J.; Westermann, B.; Ferreira, M. A. B.; Paixão, M. W.;An efficient one-pot strategy for the highly regioselective metal-free synthesis of 1,4-disubstituted-1,2,3-triazolesChem. Commun.5011926-11929(2014)DOI: 10.1039/C4CC04678A
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.