Design of plasma kallikrein inhibitors: functional and structural requirements of plasma kallikrein inhibitors.
The synthetic plasma kallikrein (PK) inhibitor trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyme thylanilide (PKSI-527) consists of three parts. Each part was replaced by analogues in an attempt to improve the potency and the selectivity of PKSI-527. Among the peptides examined, trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyan ilide (peptide 16) inhibited PK with a high selectivity and an IC50 value of 2.7 microM, being as potent as PKSI-527.
Tsuda
Y
Y
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Nishi-ku, Japan.
Wanaka
K
K
Tada
M
M
Okamoto
S
S
Hijikata-Okunomiya
A
A
Okada
Y
Y
D015195:Drug Design; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000187:drug effects; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014148:Tranexamic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D015842:Serine Proteinase Inhibitors; C064866:PKSI 527; D010649:Phenylalanine; D014148:Tranexamic Acid; D007610:Kallikreins