title: Stapled peptide-based membrane fusion inhibitors of hepatitis C virus.
abstract: The strategy of peptide stapling was used to develop new molecules to inhibit the hepatitis C virus infection via disrupting the binding of HCV envelope glycoprotein E2 with human cell surface protein CD81. The peptide sequence was designed based on the large extra-cellular loop of CD81 with known importance in the HCV E2 binding interaction. Our results showed that the stapled peptides exhibited significantly higher α-helicity and proteolytic stability as compared to their linear peptide counterpart. The optimal compound was found to have an EC50 value of ca. 17-39μM against different HCV subtypes and represented a new HCV membrane fusion inhibitor.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Hong-Kui
authors.initials: HK
authors.lastname: Cui
authors.forename: Jie
authors.initials: J
authors.lastname: Qing
authors.forename: Ye
authors.initials: Y
authors.lastname: Guo
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Wang
authors.forename: Li-Jia
authors.initials: LJ
authors.lastname: Cui
authors.forename: Tian-Hua
authors.initials: TH
authors.lastname: He
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
mesh_terms: D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides