Recognition of synthetic deoxy and deoxyfluoro analogs of the acceptor α- l-Fuc p-(1 → 2)-β- d-Gal p-OR by the blood-group A and B gene-specified glycosyltransferases

Abstract

The disaccharide α- l-Fuc p-O-(CH 2) 7CH 3 (6), is an acceptor for both glycosyltransferases responsible for the biosynthesis of the A and B blood-group antigens. These enzymes transfer GalNAc and Gal, respectively, with an α-linkage to OH-3 of the Gal residue in 6. All six possible deoxy and deoxyfluoro analogs of 6, with modifications on the target Gal residue, were chemically synthesized and kinetically evaluated as both substrates and inhibitors for the A and B glycosyltransferases. Both enzymes will tolerate replacement of the hydroxyl groups at the 3 and 6 positions of the Gal residue. Substitution of OH-4 of the Gal residue, however, abolishes recognition by these glycosyltransferases. The 6-deoxy and 6-fluoro compounds are substrates for both enzymes while the 3-deoxy and 3-flouro compounds are competitive inhibitors, with K i values in the range 14–110 μM. Kinetic constants have been determined for the 6-deoxy and 6-fluoro derivatives.