Conversion of complex sialooligosaccharides into polymeric conjugates and their anti-influenza virus inhibitory potency

To investigate the specificity of various influenza virus strains we have prepared polyacrylic type conjugates of undecasaccharide (Neu5Ac alpha2-6Gal beta1-4GlcNAc beta 2Man alpha1)(2)-3,6Man beta1 1-4GlcNAc beta1-4GlcNAc (YDS), and trisaccharides 6'-sialyl-N-acetyllactosamine (6' SLN), 6'-sialyllactose (6' SL), and 3'-sialyllactose (3' SL). Free oligosaccharides were transformed to glycosylamine-1-N-glycyl derivatives by sequential action of NH4HCO3, chloroacetic anhydride, and aqueous NH3. The known derivatization protocol has been optimized for these sialooligosaccharides. Coupling of obtained amino-spacered derivatives with poly(4-nitrophenyl acrylate) gave rise to two types of conjugates, namely with polyacrylic acid and polyacrylamide backbones; the conversion proceeded quantitatively and without destruction of the oligosaccharides. The content of oligosaccharides in the conjugates was 10, 20, and 30% mol for 3' SL, 6' SL, 6' SLN, and 2, 5 and 10% mol for YDS. Free oligosaccharides and the glycoconjugates were tested as inhibitors of influenza virus adhesion, and also as blockers of virus infectivity in MDCK cell culture. Biantennary YDS demonstrated similar activity to trisaccharide 6' SLN both as the free form and neoglycoconjugate.