Molecular Design of Spacer-N-Linked Sialoglycopolypeptide as Polymeric Inhibitors Against Influenza Virus Infection

Abstract

A series of spacer-N-linked glycopolymers carrying long/short α2,3/6 sialylated glycan were designed as polymeric inhibitors of influenza virus. Lactose (Lac) and N-acetyllactosamine (LN: Galβ1,4GlcNAc) were first converted to spacer-N-linked disaccharide glycosides, followed by consecutive enzymatic addition of GlcNAc and Gal residues to the glycosides. The resulting spacer-N-linked glycosides with di-, tetra-, and hexasaccharides carrying a Lac, LN, lacto-N-neotetraose (LNnT: Galβ1,4GlcNAcβ1,3Galβ1,4Glc), and LNβ1,3LNnT were coupled to the carboxy group of γ-polyglutamic acid (γ-PGA) and enzymatically converted to glycopolypeptides carrying α2,3/6 sialylated glycans. The interactions of a series of sialoglycopolypeptides with avian and human influenza virus strains were investigated using a hemagglutination inhibition assay. The avian virus A/Duck/HongKong/313/4/78 (H5N3) bound specifically, regardless of the structure of the asialo portion. In contrast, human virus A/Aichi/2/68 (H3N2) bound preferentially to long α2,6sialylated glycans with penta- or heptasaccharides in a glycan length-dependent manner. Furthermore, the Sambucus sieboldiana (SNA) lectin was also useful as a model of human virus hemagglutinin (HA) for understanding the carbohydrate binding properties, because the recognition motifs of the inner sugar in the receptor were very similar.

N -Glycolylneuraminic Acid on Human Epithelial Cells Prevents Entry of Influenza A Viruses That Possess N -Glycolylneuraminic Acid Binding Ability

“…Avian IAV specifically binds to Neu5Ac␣2,3Gal linkage regardless of the structure of the asialo portion. In contrast, human IAV preferentially binds to long Neu5Ac␣2,6Gal glycan with penta-or heptasaccharides in a glycan length-dependent manner (31). In our previous study, Neu5Ac and Neu5Gc binding abilities of human IAVs and HA mutant IAVs, including IAVs used in the present study, were determined by pentasaccharides containing terminal Neu5Ac or Neu5Gc (4,19).…”

Fluorescence polarization-based assay using N-glycan-conjugated quantum dots for screening in hemagglutinin blockers for influenza A viruses

“…It is well known that a variety of multivalent-type receptors bearing sialic acids show highly enhanced affinity to HAs (Feng et al, 2010;Ogata et al, 2009;Ohta et al, 2003).…”

Molecular Design of Multivalent Glycosides Bearing GlcNAc, (GlcNAc)2 and LacNAc - Analysis of Cross-linking Activities with WGA and ECA Lectins

“…Targets 12, 13 and 14 were purified by chromatography on a Bio-Gel P-2 column and an ODS column producing high yields of 71, www.intechopen.com Molecular Design of Multivalent Glycosides Bearing GlcNAc, (GlcNAc) 2 and LacNAc -Analysis of Cross-linking Activities with WGA and ECA Lectins 25 74 and 67%, respectively, based on the amount of EGTA added. The tetravalent glycosides were elucidated by 1 H and 13 C NMR analyses, as described previously [Misawa et al, 2008(b); Ogata et al, 2009]. Structures of tetravalent glycosides bearing (GlcNAc) 2 were used as a reference in the analysis of 1 H NMR spectra.…”