Tetrapeptides as potent protease inhibitors of hepatitis C virus full-length NS3 (protease-helicase/NTPase)

被引：34

作者：

Johansson, A

Poliakov, A

Åkerblom, E

Lindeberg, G

Winwarter, S

Samuelsson, B

Danielson, UH

Hallberg, A

机构：

[1] Univ Uppsala, Dept Med Chem, BMC, SE-75123 Uppsala, Sweden

[2] Univ Uppsala, Dept Biochem, BMC, SE-75123 Uppsala, Sweden

[3] Medivir AB, SE-14144 Huddinge, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2002年 / 10卷 / 12期

关键词：

D O I：

10.1016/S0968-0896(02)00310-3

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：

A library of tetrapeptides,vas evaluated for Hepatitis C Virus NS3 protease inhibitor activity in an in vitro assay system comprising the native bifunctional full-length NS3 (protease-helicase, NTPase) protein. Tetrapeptides with K-i values in the high nanomolar range were identified, for example Suc-Chg-Glu-2-Nal-Cys (K-i = 0.27+/-0.03 muM) and Suc-Dif-Glu-Glu-Cys (K-i = 0.40+/-0.10 muM). Furthermore. it as shown that the inhibitory potencies Lire not affected significantly by assay ionic strength. As suggested by molecular modelling. potential binding interactions of the tetrapeptide inhibitors with the helicase domain might explain the data and structure-activity relationships thus obtained. Hence, we postulate that the full-length NS3 assay is a relevant system for inhibitor identification. offering new opportunities for inhibitor design. (C) 2002 Elsevier Science Ltd. All rights reserved.

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页码：3915 / 3922

页数：8

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