論文 - 詳細
| RRC ID | 37670 |
|---|---|
| 著者 | Matsubara T, Sumi M, Kubota H, Taki T, Okahata Y, Sato T. |
| タイトル | Inhibition of influenza virus infections by sialylgalactose-binding peptides selected from a phage library. |
| ジャーナル | J Med Chem |
| Abstract |
Influenza virus hemagglutinin recognizes sialyloligosaccharides of glycoproteins and glycolipids as cell surface receptors in the initial stage of the infection process. We demonstrate that pentadecapeptides that bind to a sialylgalactose structure (Neu5Ac-Gal) inhibited the infection of cells by influenza virus. The pentadecapeptides were identified through affinity selection from a phage-displayed random peptide library using a monolayer of the ganglioside Neu5Acalpha2-3Galbeta1-4Glcbeta1-1'Cer (GM3). The peptides were found to have affinity for GM3, and alanine scanning showed seven amino acid residues that contribute to carbohydrate recognition. The binding of peptides to the cell surface was significantly inhibited in the presence of sialic acid or by the digestion of cell surface sialyl residues by neuraminidase. Plaque assays indicated that a molecular assembly of alkylated peptides inhibited the infection of Madin-Darby canine kidney cells by influenza virus. Carbohydrate-binding peptides that inhibit carbohydrate-virus interaction showed inhibitory activity. These results may lead to a new approach to the design of antiviral drugs. |
| 巻・号 | 52(14) |
| ページ | 4247-56 |
| 公開日 | 2009-7-23 |
| DOI | 10.1021/jm801570y |
| PMID | 19558186 |
| MeSH | Alkylation Amino Acid Sequence Animals Antiviral Agents / chemistry Antiviral Agents / metabolism* Antiviral Agents / pharmacology* Bacteriophages / metabolism Carbohydrate Sequence Cell Line Dogs Drug Evaluation, Preclinical Enzyme-Linked Immunosorbent Assay Gangliosides / chemistry Humans Influenza A virus / drug effects* Influenza A virus / physiology* Mice Molecular Sequence Data Mutagenesis Orthomyxoviridae Infections / drug therapy Peptide Library* Peptides / chemistry Peptides / genetics Peptides / metabolism* Peptides / pharmacology* Sialoglycoproteins / chemistry Sialoglycoproteins / metabolism* Virus Attachment / drug effects |
| IF | 6.205 |
| 引用数 | 42 |
| WOS 分野 | CHEMISTRY, MEDICINAL |
| リソース情報 | |
| ヒト・動物細胞 | MDCK(RCB0995) |