Chemo-enzymatic Synthesis of Oligosaccharides and Carbohydrate Mimetics PDF Download

Author: Hongmei Huang
Publisher:
ISBN:
Category : Cell adhesion
Languages : en
Pages : 610

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Book Description
Chapter I: Design and synthesis of SLe sp{\rm x} Mimetics. The design and synthesis of several SLe sp{\rm x} mimetics are described. In mimetic A, an ethylene glycol linkage bridges the fucose and galactose moieties, and a carboxymethyl group replaces the sialic acid. In mimetic B, a scD-tartaric acid derivative replaces the trans-3,4-dihydroxyl groups of the glucosamine, and links the fucose and carboxypentyl groups. These compounds were tested as inhibitors of the binding of SLe sp{\rm x} to E-selectin. Mimetic C contains a macrocyclic structure which restricts the conformation by linking the fucose and galactose moieties. Mimetic D is a glycopeptide derived from the structure of B. Mimetics C and D are expected to show better binding activities than compound A and B, respectively. Chapter II: Enzymes in organic chemistry. (1) A strategy was developed for the enzymatic solid-phase synthesis of tetrasaccharide rm NeuAc\alpha2 \to 3Gal\beta1 \to 4GlcNAc\beta1 \to 3Gal, an inhibitor of the attachment of H. pylori to mucous cells. The conversion for each step was found to be > 98%. (2) Several oligosaccharides containing negatively charged groups, sulfates or carboxylates, were synthesized for the substrate specificity study of glycosyltransferases potentially responsible for the biosynthesis of the natural ligand(s) for L-selectin. (3) Preliminary research is reported on the application of galactose oxidase for the synthesis of a potential substrate for alpha -2,3-fucosyltransferase VII, as well as other oligosaccharides. An improved procedure was developed for the GOase catalyzed oxidation of weak substrates to nearly completion. (4) A kinetics study of the lipase resolution of alcohol 82, and other nucleophiles, was performed for comparison to the antibody 21H3 catalyzed transesterification. The product inhibition and solvent effects were also discussed. (5) The regioselectivity of the transesterification of disaccharides catalyzed by enzymes such as subtilisin was investigated. Conditions were optimized to obtain either a 6 sp\prime -monoacetylated compound or a 6,6 sp\prime -diacetylated compound as the major product.