2006 Fiscal Year Final Research Report Summary
Functional design of artificial glycoconjugate by mimetics of living cell surface
| Project/Area Number |
16380077
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bioproduction chemistry/Bioorganic chemistry
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| Research Institution | Shizuoka University |
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Principal Investigator |
USUI Taich Shizuoka University, Faculty of Agriculture, Professor, 農学部, 教授 (50111802)
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| Co-Investigator(Kenkyū-buntansha) |
MURATA Takeomi Shizuoka University, Faculty of Agriculttre, Associate Professor, 農学部, 助教授 (30273171)
YAMAZAKI Masahito Shizuoka University, Faculty of Science, Professor, 理学部, 教授 (70200665)
YAMAMOTO Kenji Kyoto University, Graduate School of Biostndies, Professor, 大学院・生命科学研究科, 教授 (70109049)
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| Project Period (FY) |
2004 – 2006
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| Keywords | Glycotechnology / Glycoscience / Glycoconjugate / Glycomimetics / Molecular design / Artificial mucin / Neoglycolipid / Glycomaterial |
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| Research Abstract |
We have developed some facile synthetic methods for the preparation of biologically important glycan related oligosaccharides. Well-defined oligosaccharides, such as recognition signals, were introduced into polypeptide or lipid for constructing neoglycoconjugates to act as glycomimetics.
1. Artificial mucin
Mucins, highly glycosylated proteins that form the major component of mucosa, are known to play a physiological role as barrier to biomolecules. Highly water-soluble, artificial glycopolypeptides with a polyglutamic acid backbone carrying multivalent sialyloligosaccharide units, termed 'art+ficial mucins' have been chemoenzymatically synthesized as potential polymeric inhibitors of infection by bird and human influenza viruses. The pathway from N-acetyllactosamine or lactose was carried out by the following three steps : (1) enzymatic synthesis of a spacer-linked disaccharide glycosides ; (2) coupling of the resulting glycoside to γ-polyglutamic acid (γ-PGA) ; and (3) sialylation of
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the resulting polymers to produce highly water-soluble glycopolymers carrying clustered identical sialyldisaccharide segments. The sialylglycopolypeptides (artificial mucins) possessing Neu5Acα2-6LacNAc bound preferentially to human influenza A, whereas Neu5Acα2-3LacNAc/Lac bound to the avian influenza k The α-PGA-based sialylglycopolypeptides were useful probes for characterizing the sugar-binding specificity of hemagglutination (HA) of the Spanish influenza virus. H5N1 influenza A viruses have spread to numerous countries, infecting not only large numbers of poultry, but also an increasing number of humans.
2. Neoglycolipids
Neoglycolipids composed of a disaccharide glycoside and phospholipid were designed and prepared as mimetics of lactosylceramide. The lactosyl-and N-acetyl-lactosaminyl-phospholipids were enzymatically Synthesized from lactose and LacNAc respectively by cellulose-mediated condensation with 1,6-hexanediol, followed by conjugation of the resulting glycosides and dipalmitoylphosphatidyl choline mediated by Streptomyces phospholipase D. NMR spectroscopy indicated that the neoglycolipids in CDCl_3/CD_3OD (1/1) exist as a single molecule species, whereas in CDCl_3 they associate to form inverse micelles. X-ray diffraction showed that multilamellar vesicles (MLVs) of the neoglycolipids are in the bilayer gel phase at room temperature. These neoglycolipids have the ability to trap calcein, a chelating derivative of fluorecein, in MLVs and showed specific binding to lectin in plate assays using fluorescently labeled compounds. Such mimetics are especially attractive in the case of complex natural or synthetic glycolipids, which are expensive or difficult to obtain uniformly and /or in large amounts. Less
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