title: Inhibition of rat liver cathepsins B and L by the peptide aldehyde benzyloxycarbonyl-leucyl-leucyl-leucinal and its analogues.
abstract: Cathepsins B and L belong to the papain superfamily of cysteine proteases and play important roles in various physiological and pathological processes. In the course of studies on their inhibitors, we examined the inhibitory effects of the peptide aldehyde benzyloxycarbonyl-leucyl-leucyl-leucinal (ZLLLal) and its analogues. As a result, rat liver cathepsins B and L were shown to be strongly inhibited by them. The concentration required for 50% inhibition (IC(50)) by ZLLLal was 88 nM for cathepsin B and 163 nM for cathepsin L. Moreover, various analogues of ZLLLal, including 2-furancarbonyl-, nicotinyl-, isonicotinyl- and 4-morpholinylsuccinyl-LLLals, and some acetyl-Pro (AcP)-containing analogues, AcPLLLal and AcPPLLLal, were shown to inhibit both enzymes more strongly than ZLLLal. Among them, isonicotinyl-LLLal was most inhibitory against both cathepsins B (IC(50), 12 nM) and L (IC(50), 20 nM). Several of these inhibitors were indicated to be somewhat more soluble in aqueous media than ZLLLal.
authors.affiliation: Department of Chemistry, Faculty of Science and Engineering, Aoyama Gakuin University, Sagamihara, Kanagawa, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ito
authors.forename: Masafumi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yong-Tae
authors.initials: YT
authors.lastname: Kim
authors.forename: Kenji
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D003546:Cysteine Endopeptidases; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D007976:Leupeptins / Q000494:pharmacology*; D051381:Rats
chemical_list: D007976:Leupeptins; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde