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Biomedical subjects

W Klaffke

Publications and source records attributed to W Klaffke.

7 recordsLinked to original sources
PubMed2001

Chemoenzymatic synthesis of neoglycopeptides: application to an alpha-Gal-terminated neoglycopeptide.

A novel methodology for the enzymatic preparation from suitably derivatized oligosaccharides of N-linked neoglycopeptides using the microbial glutaminyl-peptide gamma-glutamyl transferase, transglutaminase (TGase), is described. N-Allyl glycosides of various oligosaccharides were photochemically coupled with cysteamine to yield amino-terminated thioether spacers, which were accepted by transglutaminase to transamidate the side-chain gamma-carboxamide group in the dipeptide Z-Gln-Gly.

Acylation↗
PubMed2000

Enzymatic Synthesis of Neoglycopeptide Building Blocks.

A transglutaminase-catalyzed transacylation is the major step in a practical, regioselective synthesis of N-linked spacer-modified glycopeptide analogues. The process requires minimal modification of the saccharide during the N-glycosylation, photoinduced coupling of cysteamine, and final enzymatic reaction (see scheme).

Journal Article↗
PubMed1996

Substrate specificity of native dTDP-D-glucose-4,6-dehydratase: chemo-enzymatic syntheses of artificial and naturally occurring deoxy sugars.

Incubation of dTDP-glucose with the enzyme dTDP-glucose-4,6-dehydratase [EC 4.2.1.46] from wild type E. coli B yielded a mixture of 3- and 4-keto-6-deoxy sugars after work-up. Model experiments with chemically synthesized methyl 6-deoxy-4-keto-glucoside (9) revealed that dTDP-6-deoxy-alpha-D-ribo-hexopyran-3-ulose (3) is formed by keto-enol tautomerization during the isolation procedure from initially formed dTDP-6-deoxy-alpha-D-xylo-hexopyran-4-ulose (2). dTDP-3-deoxyglucose (4) and dTDP-3-azido-3-deoxyglucose (6) were substrates and showed Michaelis-Menten kinetics (4: KM = 200 microM and V(max) = 130 mumol/h mg; 6: KM = 300 microM and V(max) = 90 mumol/h mg). In 100-mg-scale experiments, both non-natural substrates gave the respective 6-deoxy-4-keto compounds, dTDP-3,6-dideoxy-alpha-D-erythro-hexopyran-4-ulose (5) and dTDP-3-azido-3,6-dideoxy-alpha-D-xylo-hexopyran-4-ulose++ + (7), in yields ranging from 24 to 40%.

Deoxy Sugars↗
PubMed1995

Conversion of aldonic acids to their corresponding 2-keto-3-deoxy-analogs by the non-carbohydrate enzyme dihydroxy acid dehydratase (DHAD).

Aldonic acids containing four to six carbon atoms were tested as potential substrates of dihydroxy acid dehydratase (DHAD), an enzyme from the biosynthetic pathway of branched chain amino acids. Novel assay systems for observing the course of DHAD catalysed reactions were developed in order to adapt the enzyme to extended practical applications. Kinetic studies for the new substrates (12/13) as well as inhibitor kinetics for the substrate analogue 3-deoxy-aldonic acids (25, 27 and 29) were performed. These gave indications for the restrictions of substrate modifications and contributed to the understanding of the individual effects. Finally L-threonic acid (12) and D-erythronic acid (13) could be successfully applied as substrates for DHAD and this led to the chemoenzymatic synthesis of their 2-keto-3-deoxy-analogue (20) in a preparative scale.

Carbohydrate Sequence↗
PubMed1991

Approaches to the C-B-A trisaccharide of dihydroaclacinomycin by extending the chain from either side.

Selective benzylation of L-fucal (1) under phase-transfer conditions gave the 3- and 4-monoethers 2 and 3, respectively. Two routes, the "tail" or the "head" addition are presented, both leading to the target molecule 9, a mimic of the C-B-A trisaccharide component of dihydroaclacinomycin. Addition of glycals 2 and 3 respectively, to the acetylated glycal (7) of amicetose used as glycosyl donor gave the disaccharide glycals 6 and 8. Alternatively, glucosylation of the 4-acetate (4) of 2 with the benzyl hex-2-enopyranoside derivative 10 gave the disaccharide derivative 11. In the first case, the final glycosylation step involves the addition of 10 to disaccharide glycal 8. In the second procedure, the disaccharide alcohol 12 is obtained by O-deacetylation of 11, and serves as the glycosyl acceptor for glycal derivative 7 to give the C-B-a precursor trisaccharide derivative.

Aclarubicin↗
PubMedDate not supplied

Iterated reaction graphs: simulating complex Maillard reaction pathways.

This study investigates a new method of simulating a complex chemical system including feedback loops and parallel reactions. The practical purpose of this approach is to model the actual reactions that take place in the Maillard process, a set of food browning reactions, in sufficient detail to be able to predict the volatile composition of the Maillard products. The developed framework, called iterated reaction graphs, consists of two main elements: a soup of molecules and a reaction base of Maillard reactions. An iterative process loops through the reaction base, taking reactants from and feeding products back to the soup. This produces a reaction graph, with molecules as nodes and reactions as arcs. The iterated reaction graph is updated and validated by comparing output with the main products found by classical gas-chromatographic/mass spectrometric analysis. To ensure a realistic output and convergence to desired volatiles only, the approach contains a number of novel elements: rate kinetics are treated as reaction probabilities; only a subset of the true chemistry is modeled; and the reactions are blocked into groups.

Aldehydes↗