RECOGNITION OF SYNTHETIC DEOXY AND DEOXYFLUORO ANALOGS OF THE ACCEPTOR ALPHA-L-FUCP-(1-]2)-BETA-D-GALP-OR BY THE BLOOD-GROUP-A AND BLOOD-GROUP-B GENE-SPECIFIED GLYCOSYLTRANSFERASES

The disaccharide alpha-L-Fuc p-(1 --> 2)-beta-D-Gal p-O-(CH2)7CH3 (6), is an acceptor for both glycosyl-transferases responsible for the bio synthesis of the A and B blood-group antigens. These enzymes transfer GalNAc and Gal, respectively, with an alpha-linkage to OH-3 of the Gal residue in 6. All six possible deoxy and deoxyfluoro analogs of 6, wi th modifications on the target Gal residue, were chemically synthesize d and kinetically evaluated as both substrates and inhibitors for the A and B glycosyltransferases. Both enzymes will tolerate replacement o f the hydroxyl groups at the 3 and 6 positions of the Gal residue. Sub stitution of OH-4 of the Gal residue, however, abolishes recognition b y these glycosyltransferases. The 6-deoxy and 6-fluoro compounds are s ubstrates for both enzymes while the 3-deoxy and 3-fluoro compounds ar e competitive inhibitors, with K(i) values in the range 14-110 muM. Ki netic constants have been determined for the 6-deoxy and 6-fluoro deri vatives.