title: Novel epoxysuccinyl peptides. Selective inhibitors of cathepsin B, in vitro.
abstract: 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-proli ne (compound CA-030) and N-(L-3-trans-propylcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-prol ine (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 the 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.
authors.affiliation: Research Center, Taisho Pharmaceutical Co., Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Murata
authors.forename: S
authors.initials: S
authors.lastname: Miyashita
authors.forename: C
authors.initials: C
authors.lastname: Yokoo
authors.forename: M
authors.initials: M
authors.lastname: Tamai
authors.forename: K
authors.initials: K
authors.lastname: Hanada
authors.forename: K
authors.initials: K
authors.lastname: Hatayama
authors.forename: T
authors.initials: T
authors.lastname: Towatari
authors.forename: T
authors.initials: T
authors.lastname: Nikawa
authors.forename: N
authors.initials: N
authors.lastname: Katunuma
mesh_terms: D000818:Animals; D002154:Calpain / Q000737:chemistry; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D056655:Cathepsin H; D056668:Cathepsin L; D002403:Cathepsins / Q000737:chemistry; D003546:Cysteine Endopeptidases; D004151:Dipeptides / Q000494:pharmacology*; D010450:Endopeptidases; D066298:In Vitro Techniques; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats
chemical_list: D004151:Dipeptides; C068249:N-(3-ethoxycarbonyloxirane-2-carbonyl)-isoleucyl-proline; C068250:N-(3-propylcarbamoyloxirane-2-carbonyl)-isoleucyl-proline; D002403:Cathepsins; D010450:Endopeptidases; D002154:Calpain; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat; D056655:Cathepsin H; C534128:Ctsh protein, rat; D007930:Leucine; C024974:E 64