Stapled peptide-based membrane fusion inhibitors of hepatitis C virus

被引：60

作者：

Cui, Hong-Kui ^{[1
]}

Qing, Jie ^{[1
]}

Guo, Ye ^{[1
]}

Wang, Yu-Jia ^{[1
]}

Cui, Li-Jia ^{[2
,3
]}

He, Tian-Hua ^{[2
,3
]}

Zhang, Linqi ^{[2
,3
]}

Liu, Lei ^{[1
]}

机构：

[1] Tsinghua Univ, Dept Chem, Tsinghua Peking Ctr Life Sci,Minist Educ, Key Lab Bioorgan Phosphorus Chem & Chem Biol, Beijing 100084, Peoples R China

[2] Tsinghua Univ, Sch Med, Comprehens AIDS Res Ctr, Beijing 100084, Peoples R China

[3] Tsinghua Univ, Sch Med, Res Ctr Publ Hlth, Beijing 100084, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 12期

基金：

中国国家自然科学基金;

关键词：

Hepatitis C virus; Stapled peptide; Protein-protein interaction; CELL-CULTURE SYSTEMS; B TYPE-I; OLEFIN METATHESIS; ALPHA-HELICES; BH3; HELIX; CD81; ENTRY; INFECTION; PROTEINS; RECEPTOR;

D O I：

10.1016/j.bmc.2013.02.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 alpha-helicity and proteolytic stability as compared to their linear peptide counterpart. The optimal compound was found to have an EC50 value of ca. 17-39 mu M against different HCV subtypes and represented a new HCV membrane fusion inhibitor. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：3547 / 3554

页数：8

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