HIGH-PERFORMANCE POLYMER SUPPORTS FOR ENZYME-ASSISTED SYNTHESIS OF GLYCOCONJUGATES

Efficient and practical methodology for the construction of carbohydra tes, including oligosaccharide derivatives and sphingoglycolipids, was established on the basis of a water-soluble polymer supports having u nique linkers that can be cleaved by specific conditions. Novel glycom onomers for the construction of polymer supports were synthesized and copolymerized with acrylamide to give three types of water-soluble gly copolymers having primer sugars through the specific linkers containin g (i) p-substituted benzyl group, (ii) L-phenylalanine residue, and (i ii) ceramide-mimetic L-serine derivative, respectively. These glycopol ymers were employed for sugar elongation reactions with glycosyl trans ferases such as GlcNAc beta 1,4-galactosyl transferase, beta Gal1-->3/ 4GlcNAc alpha-2,6-sialyl transferase, and beta Gal1-->3/4GlcNAc alpha- 2,3-sialyl transferase in the presence of each sugar nucleotide as gly cosyl donor to afford polymers having N-acetyllactosamine, sialyl alph a-(2-->6) N-acetyllactosamine, and sialyl alpha-(2-->3) lactose residu es in excellent yield. Subsequent hydrogenolysis, hydrolysis with alph a-chymotrypsin, or transglycosylation to ceramide with ceramide glycan ase proceeds smoothly to give N-acetyllactosamine, a versatile sialyl alpha-(2-->6) N-acetyllactosamine derivative having a terminal amino g roup, and ganglioside GM3 in high yield. (C) 1998 Elsevier Science Ltd .