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

• Published in: Biomacromolecules 2009-07, Vol.10 (7), p.1894-1903
• Main Authors: Ogata, Makoto, Hidari, Kazuya I. P. J, Kozaki, Wataru, Murata, Takeomi, Hiratake, Jun, Park, Enoch Y, Suzuki, Takashi, Usui, Taichi
• Format: Article
• Language: English
• Subjects: Alphainfluenzavirus - drug effects; Aminoacid polymers; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Applied sciences; Biological and medical sciences; Drug Design; Ducks; Exact sciences and technology; Hemagglutination Inhibition Tests; Humans; Influenza A Virus, H3N2 Subtype; Influenza in Birds - drug therapy; Influenza in Birds - prevention & control; Influenza virus; Influenza, Human - drug therapy; Influenza, Human - prevention & control; Medical sciences; Pharmacology. Drug treatments; Physicochemistry of polymers; Sambucus; Sialoglycoproteins - chemical synthesis; Sialoglycoproteins - pharmacology; Sialoglycoproteins - therapeutic use; Synthetic biopolymers
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm900300j

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.