Novel epoxysuccinyl peptides A selective inhibitor of cathepsin B, in vivo

FEBS Letters

Towatari, Takae¹  Katunuma, Nobuhiko¹  Tamai, Masaharu²  Murata, Mitsuo²  Nikawa, Takeshi¹  Hanada, Kazunori²  Yokoo, Chihiro² 

[1] Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Tokushima 770 Japan;Research Center, Taisho Pharmaceutical Co. Ltd., 1-403 Toshino-chow, Ohmiya, Saitama 330, Japan

关键词: Cysteine proteinase inhibitory E-64 derivative;    Cathepsin B;    Cathepsin L;    Cathepsin H;    Cysteine proteinase;    Z;    benzyloxycarbonyl;    MCA;    methylcoumarylamide;    BCA;    bicinchoninic acid;    E-64-a;    N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucine-4-aminobutylamide;    E-64-c;    N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucine-3-methylbutylamide;    CA-028;    N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-isoleucyl-L-proline;    CA-030;    N-(L-3-trans-Ethoxycarbonyloxirane-2-carbonyl)-L-isoleucyl-L-proline;    CA-074;    N-(L-3-trans-Propylcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-proline;    tES;    L-trans-epoxysuccinyl;    IAA;    isoamylamide;    Pr11NH;    n-propylamide;   

DOI  :  10.1016/0014-5793(91)80319-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

New derivatives of E-64 (compound CA-030 and CA-074) were tested in vitro and in vivo for selective inhibition of cathepsin B. They exhibited 10000–30000 times greater inhibitory effects on purified rat cathepsin B than on cathepsin H and L; their initial K ₁ values for cathepsin B were about 2–5 nM, like that of E-64-c, whereas their initial K ₁ values for cathepsins H and L were about 40–200 μM. In in vivo conditions, such us intraperitoneal injection of compound CA-030 or CA-074 into rats, compound CA-074 is an especially potent selective inhibitor of cathepsin B, whereas compound CA-030 does not show selectivity for cathepsin B, although both compounds CA-030 and CA-074 show complete selectivity for cathepsin B in vitro.

【 授权许可】

Unknown