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.
Department of Bioscience, Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga ward, Shizuoka 422-8529, Japan.
Makoto
M
Ogata
Kazuya I P J
KI
Hidari
Wataru
W
Kozaki
Takeomi
T
Murata
Jun
J
Hiratake
Enoch Y
EY
Park
Takashi
T
Suzuki
Taichi
T
Usui
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