Formation of LacNAc mimetics employing novel donor substrates for enzymatic β1→4 galactosylation

Abstract

In examining C-6 modified 4-nitrophenyl beta-D-galactopyranosides as donor structures the beta-galactosidase (Bacillus circulans) revealed an unexpectedly broad substrate specificity which allowed successful syntheses of various disaccharide components.

Combined Application of Galactose Oxidase and β‐N‐Acetylhexosaminidase in the Synthesis of Complex Immunoactive N‐Acetyl‐D‐galactosaminides

“…[4,16] The problem of using galactose oxidase is the oxygen supply. Although a simple diffusive gas transport through the solution surface is mostly used in the literature, [9,17] the yields turned to be unsatisfactory in our hands. Bubbling by air or oxygen quickly deactivates the enzyme, probably due to denaturation in the gas/liquid interphase area.…”

“…They tolerate environmental stress and have a broad substrate specificity towards a variety of acceptors. [5,7,9] The introduction of a highly reactive functionality such as the aldehyde group brings about the possibility of further modifications, e.g., reduction, oxidation or conjugation (e.g., with amines or hydrazides). [1b,4] The first papers presenting the use of modified glycosyl donors with glycosidases were published in the late 1990 s, [5,6] the first use of a b-N-acetylhexosaminidase was demonstrated by Hušáková et al [7] in a reaction with 6-O-acetylated glycosyl donors.…”

“…Their application is somehow limited in respect of glycosyl donors contrary to glycosyl transferases where a large number of modified substrates -nucleotide sugars -were employed for synthetic purposes. [4c] It was already demonstrated that some galactosidases can tolerate the aldehyde group [5,9] and are able to use such modified substrates for transglycosylation reactions. A series of b-Nacetylhexosaminidases with a broad substrate specificity was identified in a recent study dealing with p-nitrophenyl 2-acylamido-2-deoxy-b-d-glucopyranosides.…”

“…However, a large group of well-accepted modifications in the pyranose ring are those at the C-6 position. [5,7,9] The introduction of a highly reactive functionality such as the aldehyde group brings about the possibility of further modifications, e.g., reduction, oxidation or conjugation (e.g., with amines or hydrazides). The latter has recently been accomplished by the use of biotinylated nucleotide sugars as substrates for glycosyl transferases.…”

Glycosidases in Carbohydrate Synthesis: When Organic Chemistry Falls Short

“…6). [39c] Weingarten and Thiem [42] also developed this topic by presenting nine C(6) modified glycosides (e.g. 7, 8) as potential substrates for the b-galactosidase from Bacillus circulans.…”