Inhibition of Influenza Virus Infections by Sialylgalactose-Binding Peptides Selected from a Phage Library
Inhibition of Influenza Virus Infections by Sialylgalactose-Binding Peptides Selected from a Phage Library
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DOI：
10.1021/jm801570y
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发表时间：
2009-07-23
影响因子：
7.3
通讯作者：
Sato, Toshinori
中科院分区：
文献类型：
--
作者：
Matsubara, Teruhiko;Sumi, Machiko;Sato, Toshinori
流感病毒血凝素在感染过程的初始阶段识别糖蛋白和糖脂的唾液寡糖作为细胞表面受体。我们证明了与唾液基半乳糖结构结合的五肽（Neu5Ac-Gal）抑制流感病毒对细胞的感染。利用神经节苷脂Neu5Ac α 2-3Gal β 1-4Glc β 1-1'Cer （GM3）单层，通过亲和选择从噬菌体展示的随机肽库中鉴定出五肽。这些肽被发现对GM3有亲和力，丙氨酸扫描显示了7个氨基酸残基有助于碳水化合物识别。在唾液酸存在或神经氨酸酶消化细胞表面唾液残基时，多肽与细胞表面的结合被显著抑制。斑块实验表明，烷基化多肽的分子组装抑制了流感病毒对Madin-Darby犬肾细胞的感染。抑制碳水化合物与病毒相互作用的碳水化合物结合肽显示出抑制活性。这些结果可能会导致抗病毒药物设计的新方法。
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 Neu5Ac alpha 2-3Gal beta 1-4Glc beta 1-1'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 or 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.