Molecular design of spacer-N-linked sialoglycopolypeptide as polymeric inhibitors against influenza virus infection.
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.
Ogata
Makoto
M
Department of Bioscience, Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga ward, Shizuoka 422-8529, Japan.
Hidari
Kazuya I P J
KI
Kozaki
Wataru
W
Murata
Takeomi
T
Hiratake
Jun
J
Park
Enoch Y
EY
Suzuki
Takashi
T
Usui
Taichi
T
D000818:Animals; D015195:Drug Design; D004372:Ducks; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype; D005585:Influenza in Birds / Q000188:drug therapy* / Q000517:prevention & control; D007251:Influenza, Human / Q000188:drug therapy* / Q000517:prevention & control*; D029521:Alphainfluenzavirus / Q000187:drug effects*; D012795:Sialoglycoproteins / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use
D012795:Sialoglycoproteins