title: Development of active center-directed inhibitors against plasmin.
abstract: Active center-directed inhibitors of plasmin were designed based on the structure of specific substrates of plasmin and then synthesized. Their effects on plasmin were examined and the structure-inhibitory activity relationship was studied. N alpha-trans-4-Aminomethylcyclohexanecarbonyllysine 4-benzoylanilide (Tra-Lys-BZA) inhibited plasmin activities toward S-2251 and fibrin with IC50 values of 15 and 6.1 microM, respectively and N alpha-trans-4-aminomethylcyclohexane-carbonyllysine 4-benzylpiperidine amide (Tra-Lys-BPP) did not show any detectable inhibitory activity. Moreover, it was revealed that Tra-Lys-4-methoxycarbonylanilide inhibited plasma kallikrein more potently than plasmin.
authors.affiliation: Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Teno
authors.forename: K
authors.initials: K
authors.lastname: Wanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuda
authors.forename: U
authors.initials: U
authors.lastname: Okamoto
authors.forename: A
authors.initials: A
authors.lastname: Hijikata-Okunomiya
authors.forename: T
authors.initials: T
authors.lastname: Naito
authors.forename: S
authors.initials: S
authors.lastname: Okamoto
mesh_terms: D001665:Binding Sites; D005341:Fibrinolysin / Q000037:antagonists & inhibitors*
chemical_list: D005341:Fibrinolysin