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.