Increased expression of the selectin ligand sialyl-Lewis(x) by biochemical engineering of sialic acids

Abstract

Sialylation of glycoproteins and glycolipids plays an important role during development, regeneration and pathogenesis of several diseases. The precursor of all physiological sialic acids is N-acetyl-d-mannosamine. Using N-propanoyl mannosamine, a novel precursor of sialic acid, we showed earlier that sialic acids with a prolonged N-acyl side chain (e.g., N-propanoyl neuraminic acid) are incorporated into cell surface glycoconjugates. In this study, we report the structural and functional consequences of the incorporation of the nonphysiological sialic acid, N-propanoyl neuraminic acid, into glycoconjugates of HL60-I cells. These cells do not express UDP-GlcAc-2-epimerase, the key enzyme of the biosynthesis of N-acetyl-d-mannosamine. Therefore, they do not express sialyl-Lewis(x) structures and consequently do not bind to selectins. Application of N-acetyl-d-mannosamine leads to the expression of sialyl-Lewis(x) structures and to binding to selectins. Surprisingly, incorporation of N-propanoyl neuraminic acid into glycoconjugates of these cells leads to a dramatic increase of sialyl-Lewis(x) structures and to increased adhesion to selectins.