title: Development of selective inhibitors against plasma kallikrein.
abstract: Specific plasma kallikrein inhibitors were designed and synthesized and their structure-activity relationship was studied. trans-4-Aminomethylcyclohexanecarbonyl (Tra)-lysyl-4-ethoxycarbonylanilide inhibited plasma kallikrein and plasmin with IC50 values of 23 and 210 microM, respectively, indicating that this compound is fairly specific to plasma kallikrein. Tra-arginyl-4-ethoxycarbonylanilide inhibited plasma kallikrein and plasmin with IC50 values of 16 and 480 microM, respectively. Tra-homoarginyl-4-carboxyanilide inhibited plasma kallikrein and plasmin with IC50 values of 14 microM and 1 mM, respectively. Finally, Tra-Arg(Mts)-4-acetylanilide (ACA) exhibited potent and selective inhibitory activity against plasma kallikrein (IC50 value for plasma kallikrein: 2 microM and for plasmin: 42 microM).
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: D000595:Amino Acid Sequence; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000097:blood; D008969:Molecular Sequence Data; D013917:Thrombin / Q000037:antagonists & inhibitors
chemical_list: D007610:Kallikreins; D013917:Thrombin; D005341:Fibrinolysin