ACCEPTOR HYDROXYL GROUP MAPPING FOR CALF THYMUS ALPHA-(1-]3)-GALACTOSYLTRANSFERASE AND ENZYMATIC-SYNTHESIS OF HA-D-GALP-(1-]3)-BETA-D-GALP-(1-]4)-BETA-D-GLCPNAC ANALOGS

The epitope of the acceptor substrate for alpha-(1-->3)-galactosyItran sferase from calf thymus has been mapped by using a series of mono-deo xygenated and mono-O-alkylated Type II (beta-D-Galp-(1-->4)-beta-D-Glc pNAc) disaccharides. The 4-OH group of the beta-D-galactopyranosyl res idue is a key polar group essential for glycosyl transfer, tolerating neither deoxygenation nor O-alkylation. Substitution at positions 6 an d 6' by a variety of polar alkyl substituents was readily tolerated, a llowing the preparative enzymatic synthesis of a series of trisacchari de derivatives carrying polar substituents on each of these hydroxyl g roups. These new analogs are potential inhibitors of Clostridium diffi cile toxin A and of a human anti-alpha-Gal antibody. (C) 1998 Elsevier Science Ltd.