Large-Scale Chemical and Enzymatic Synthesis of a Clostridium difficile Toxin A Binding Trisaccharide [1]

Abstract

Trisaccharide 1, 8-methoxycarbonyloctyl-O-(α-d-galactopyranosyl)-(1→3)-(β-d-galactopyranosyl)-(1→4)-β-d-glucopyranoside, linked to a solid support can be used to remove Clostridium difficile toxin A from the intestinal tract. Therefore, multi-gram chemical and enzymatic synthesis of the toxin binding trisaccharide 1 from 8-methoxycarbonyloctyl β-lactoside disaccharide 2 were explored. Chemical conversion in 30% overall yield could be achieved in seven steps. Alternatively a single step enzymatic conversion of the lactoside using recombinant α(1→3)-galactosyltransferase with UDP-galactose or UDP-glucose/UDP-Glc epimerase gave 1 in 85-90% yield.

Key words

Clostridium difficile toxin A - galactosyltransferase - iso-globo trisaccharide - Gal(α1,3)Gal epitope

1

Presented, in part, at the 4th Carbohydrate Bioengineering Meeting Stockholm Sweden, June 10-13, 2001.

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1

Presented, in part, at the 4th Carbohydrate Bioengineering Meeting Stockholm Sweden, June 10-13, 2001.