title: Synthesis of trans-4-aminomethylcyclohexanecarbonyl-L- and -D-phenylalanine-4-carboxymethylanilide and examination of their inhibitory activity against plasma kallikrein.
abstract: Based on studies of structure-activity relationship, trans-4-aminomethylcyclohexanecarbonyl-L-phenylalanine-4-carbox ymethylanilide (Tra-Phe-APAA) was designed as a selective plasma kallikrein inhibitor and synthesized. Tra-Phe-APAA inhibited plasma kallikrein with a Ki value of 0.81 microM, while it inhibited glandular kallikrein, plasmin, urokinase, factor Xa and thrombin with Ki values of greater than 500, 390, 200, greater than 500, and greater than 500 microM, respectively. However, its stereoisomer, Tra-D-Phe-APPA did not exhibit any detectable inhibitory activity against the above enzymes.
authors.affiliation: Kobe Research Projects on Thrombosis and Haemostasis, Japan.
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: S
authors.initials: S
authors.lastname: Okamoto
mesh_terms: D000818:Animals; D002417:Cattle; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism; D014148:Tranexamic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: C064866:PKSI 527; D010649:Phenylalanine; D014148:Tranexamic Acid; D007610:Kallikreins