Chemoenzymatic synthesis and application of glycopolymers containing multivalent sialyloligosaccharides with a poly(L-glutamic acid) backbone for inhibition of infection by influenza viruses

K. Totani
2002 Glycobiology  
Highly water-soluble glycopolymers with poly(a-L-glutamic acid) (PGA) backbones carrying multivalent sialyl oligosaccharides units were chemoenzymatically synthesized as polymeric inhibitors of infection by human influenza viruses. p-Aminophenyl disaccharide glycosides were coupled with g-carboxyl groups of PGA side chains and enzymatically converted to Neu5Aca2-3Galb1-4GlcNAcb-, Neu5Aca2-6Galb1-4GlcNAcb-, Neu5Aca2-3Galb1-3GalNAca-, and Neu5Aca2-3Galb1-3GalNAcb-units, respectively, by a2,3or
more » ... 6-sialytransferases. The glycopolymers synthesized were used for neutralization of human influenza A and B virus infection as assessed by measurement of the degree of cytopathic inhibitory effect in virus-infected MDCK cells. Among the glycopolymers tested, a2,6-sialo-PGA with a high molecular weight (260 kDa) most significantly inhibited infection by an influenza A virus, strain A/Memphis/1/71 (H3N2), which predominantly binds to a2-6 Neu5Ac residue. The a2,6-sialo-PGA also inhibited infection by an influenza B virus, B/Lee/40. The binding preference of viruses to terminal sialic acids was affected by core determinants of the sugar chain, Galb1-4GlcNAcb-or Galb1-3GalNAca/b-units. Inhibition of infection by viruses was remarkably enhanced by increasing the molecular weight and sialic acid content of glycopolymers.
doi:10.1093/glycob/cwg032 pmid:12626382 fatcat:tqxbkpkm2vbqdgkfubdgy7mxbm