Sialic Acid-Mimic Peptides As Hemagglutinin Inhibitors for Anti-Influenza Therapy
Sialic Acid-Mimic Peptides As Hemagglutinin Inhibitors for Anti-Influenza Therapy
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DOI：
10.1021/jm1002183
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发表时间：
2010-06-10
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;Onishi, Ai;Sato, Toshinori
流感是一种由流感病毒引起的传染病，每年有许多人患有这种疾病。甲型流感病毒膜上的血凝素(HA)在感染过程的最初阶段识别宿主细胞表面的唾液酸糖结合受体，因此，HA抑制剂被认为是潜在的抗病毒药物。我们通过从噬菌体展示的随机多肽文库中进行多序列选择，鉴定了与受体结合位点结合的多肽。以H1株和H3株的血凝素为靶蛋白，获得了与两株HAS结合的多肽。通过从相应的亚库中进行二级和三级选择，这些H AS的多肽的结合亲和力得到了改善。对接模拟表明，与唾液酸类似，这些多肽是由HA中的受体结合部位识别的，这表明这些多肽模仿唾液酸结构。N-硬脂酰多肽可抑制A/波多黎各/8/34(H1N1)和A/Aichi/2/68(H3N2)流感病毒株的感染。这些HA抑制剂是很有希望成为新型抗病毒药物的候选药物。
Influenza is an infectious disease caused by the influenza virus, and each year many people suffer from this disease. Hemagglutinin (HA) in the membrane of type A influenza viruses recognizes sialylglyco-conjugate receptors on the host cell surface at an initial step in the infection process; consequently, HA inhibitors are considered potential candidates for antiviral drugs. We identified peptides that bind to receptor-binding sites through a multiple serial selection from phage-displayed random peptide libraries. Using the HA of the H1 and H3 strains as target proteins, we obtained peptides that bind to both H As. The binding affinities of peptides for these H As were improved by secondary and tertiary selections from the corresponding sublibraries. A docking simulation suggested that, similar to sialic acid, the peptides are recognized by the receptor-binding site in HA, which indicates that these peptides mimic the sialic acid structure. N-stearoyl peptides inhibited infections by the A/Puerto Rico/8/34 (H1N1) and A/Aichi/2/68 (H3N2) strains of influenza virus. Such HA-inhibitors are promising candidates for novel antiviral drugs.