Stapled peptide-based membrane fusion inhibitors of hepatitis C virus

被引：61
|
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
收藏
页码：3547 / 3554
页数：8
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