Novel epoxysuccinyl peptides Selective inhibitors of cathepsin B, in vitro

FEBS Letters

Towatari, Takae²  Hatayama, Katsuo¹  Katunuma, Nobuhiko²  Murata, Mitsuo¹  Nikawa, Takeshi²  Miyashita, Satsuki¹  Tamai, Musaharu¹  Hanada, Kazunori¹  Yokoo, Chihiro¹ 

[1]Research Center, Taisho Pharmaceutical Co., 1-403 Yoshino-cho, Omiya, Saitama 330 Japan

[2]Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Tokushima, Japan

关键词: Epoxysuccinyl peptide;    Cathepsin B;    Cysteine proteinase;    Specific inhibitor;    Z;    benzyloxycarbonyl;    MCA;    methylcoumarylamide;    E-64-c (Ep-475);    N-(L-3-trans-Carboxyoxirane-2-carbonyl)-L-leucine-3-methylbutylamide;    E-64-d (EST or Loxistatin);    N-(L-3-trans-Ethoxycarbonyloxirane-2-carbonyl)-L-leucine-3-methylbutylamide;   

DOI  :  10.1016/0014-5793(91)80318-W

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A series of new epoxysuccinyl peptides were designed and synthesized to develop a specific inhibitor of cathepsin B. Of these compounds, N-(L-3-trans-ethoxycarbonyloxirane-2-carbonyl)-L-isoleucyl-L-proline (compound CA-030) and N-(L-3-trans-propylcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-proline (compound CA-074) were the most potent and specific inhibitors of cathepsin B in vitro. The carboxyl group of proline and the ethyl ester group or n-propylamide group in the oxirane ring were necessary, the ethyl ester group or the n-propylamide group being particularly effective for distinguishing cathepsin B from other cysteine proteinases such as cathepsins L and H, and calpains.

【 授权许可】

Unknown