Chemoenzymatic Synthesis of Well-Defined α(2,8)- and α(2,9)-linked Oligosialosides

Abstract

A chemoenzymatic strategy is described that can readily provide well-defined α(2,8)- and α(2,9)-linked oligosialic acids of different length. It employs the recombinant bacterial sialic acid polymerases, NmC-PST and NmB-PST, in combination with cytidine 5’-monophosphate N-acetylneuraminic acid (CMP-Neu5Ac) derivatives that have a benzoyl ester at C-9 or thioethyl ether at the C-5 acetamide of Neu5Ac. It results in products that lack glycosyl accepting properties and hence prevent polymerization. The benzoyl ester can be removed by mild basic hydrolysis and the thioethyl ether by reductive desulfurization to give natural Neu5Ac than can be extended in a next cycle of enzymatic sialylation and unmasking. The resulting oligosialosides are attractive materials for the development of bacterial vaccine and as probes to investigate the roles of oligosialosides in human physiology.