Recognition of synthetic O-methyl, epimeric, and amino analogues of the acceptor α-L-Fuc p-(1→)-β-D-Galp-OR by the blood-group A and B gene-specified glycosyltransferases

The disaccharide α-L-Fuc p-(1→2)-β-D-Galp-O-(CH 2 ) 7 CH 3 (6) is an acceptor for the glycosyltransferases responsible for the biosynthesis of the A and 13 blood-group antigens. These enzymes respectively transfer GalNAc and Gal in an α linkage to OH-3 of the Gal residue in 6. All eight possible O-methyl, epimeric, and amino analogues of 6 having modifications on the target Gal residue were chemically synthesized and kinetically evaluated both as substrates and inhibitors for the A and B glycosyltransferases. The results support earlier findings that both enzymes will tolerate replacement of the hydroxyl groups at the 3 and 6 positions of the Gal residue. Substitution at or replacement of OH-4 of the Gal residue, however abolishes recognition. The 6-O-methyl and 6-amino compounds are substrates for both enzymes while the 3-epimeric (10) and 3-amino (12) compounds are inhibitors