Non‐peptide inhibitors of HCV serine proteinase

FEBS Letters

Komoda, Keiko²  Shimotohno, Kunitada¹  Kakiuchi, Nobuko²  Tani, Tadato²  Okada, Satoshi²  Komoda, Yasumasa²  Takeshita, Norisue² 

[1] Institute for Virus Research, Kyoto University, Kyoto 606-01, Japan;HQL Research Laboratories, Sumitomo Metal Industries, Kyoto 619-02, Japan

关键词: Hepatitis C virus;    Proteinase inhibitor;    Non-peptide compound;    Ac;    acetyl;    Boc;    t-butyloxycarbonyl;    Bz;    benzoyl;    DMSO;    dimethyl sulfoxide;    Dns;    dansyl;    DTT;    dithiothreitol;    ELISA;    enzyme-linked immunosorbent assay;    HCV;    hepatitis C virus;    HPLC;    high-performance liquid chromatography;    MBP;    maltose binding protein;    MCA;    4-methyl-coumaryl-7-amide;    NS;    non-structural protein;    pNA;    p-nitroanilide;    Pyr;    l-pyroglutamyl;    SDS;    sodium dodecylsulfate;    Suc;    succinyl;    Z;    carbobenzoxy;   

DOI  :  10.1016/S0014-5793(97)01566-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We screened a chemical library of 2000 compounds for inhibitors of hepatitis C virus (HCV) serine proteinase using an in vitro screening method measuring the hydrolysis of the peptide substrate. Three compounds were found to be the most potent inhibitors (IC₅₀<10⁻⁵ M). Two of them had a similar structure, that of halogenated benzanilide, and were not inhibitory for common serine proteinases. They inhibited the enzyme non-competitively with the substrate. Together with the result of the analogous compounds in the chemical library, the presumed structural requirements of the inhibition are pointed out.

【 授权许可】

Unknown