High performance polymer supports for enzyme-assisted synthesis of glycoconjugates

Abstract

Efficient and practical methodology for the construction of carbohydrates, including oligosaccharide derivatives and sphingoglycolipids, was established on the basis of a watersoluble polymer supports having unique linkers that can be cleaved by specific conditions. Novel glycomonomers for the construction of polymer supports were synthesized and copolymerized with acrylamide to give three types of water-soluble glycopolymers having primer sugars through the specific linkers containing (i) p-substituted benzyl group, (ii) l-phenylalanine residue, and (iii) ceramide-mimetic l-serine derivative, respectively. These glycopolymers were employed for sugar elongation reactions with glycosyl transferases such as GlcNAc β1,4-galactosyl transferase, βGall → 3/4GlcNAc α-2,6-sialyl transferase, and βGall → 3/4GlcNAc α-2,3-sialyl transferase in the presence of each sugar nucleotide as glycosyl donor to afford polymers having N-acetyllactosamine, sialyl α-(2 → 6) N-acetyllactosamine, and sialyl α-(2 → 3) lactose residues in excellent yield. Subsequent hydrogenolysis, hydrolysis with α-chymotrypsin, or transglycosylation to ceramide with ceramide glycanase proceeds smoothly to give N-acetyllactosamine, a versatile sialyl α-(2 → 6) N-acetyllactosamine derivative having a terminal amino group, and ganglioside GM3 in high yield.