Acceptor hydroxyl group mapping for calf thymus α-(1 → 3) - galactosyltransferase and enzymatic synthesis of [formula omitted][formula omitted] analogs

Abstract

The epitope of the acceptor substrate for α-(1 → 3)-galactosyltransferase from calf thymus has been mapped by using a series of mono-deoxygenated and mono- O-alkylated Type II (β- d- Galp-(1 → 4)-β- d- Glcp NAc) disaccharides. The 4-OH group of the β- d-galactopyranosyl residue is a key polar group essential for glycosyl transfer, tolerating neither deoxygenation nor O-alkylation. Substitution at positions 6 and 6′ by a variety of polar alkyl substituents was readily tolerated, allowing the preparative enzymatic synthesis of a series of trisaccharide derivatives carrying polar substituents on each of these hydroxyl groups. These new analogs are potential inhibitors of Clostridium difficile toxin A and of a human anti-α-Gal antibody.