A facile synthetic approach to L- and P-selectin blockers via copolymerization of vinyl monomers constructing the key carbohydrate modules of Sialyl Lewis^x mimics

A highly practical synthetic approach is described for artificial L- and P-selectin blockers. The synthesis involves radical bi- and terpolymerizations of p-(N-acrylamido)phenyl 3- or/and 6-sulfo-β-D-galactoside with allyl α-L-fucoside in the presence of acrylamide. Each of the two glycosyl monomers constructs a key carbohydrate module responsible for selectins/sulfated sialyl Lewis^x (sLe^x) bindings. Whereas an acrylamide copolymer carrying 3-sulfo-galactoside showed no activity for any selectins, the fucosylated terpolymer showed a potent activity to block both of P- and L-selectins/sLe^x binding at a concentration of a few micrograms per milliliter. The enhanced activity is apparently ascribed to the cooperative binding effects of the fucoside and the 3-sulfo-galactoside residues.