Studies of angiotensin I converting enzyme: effects of kinins, bacitracin, γ-aminobutyric and ε-aminocaproic acids, and related compounds on substrate binding and catalysis in vitro

Abstract

Bradykinin and 22 of its analogs were evaluated for their abilities to inhibit the hydrolysis of [3H]hippurylglycylglycine by purified porcine kidney angiotensin I converting enzyme. The mean inhibitory concentration (IC50) for bradykinin was 1.2 ± 0.2 × 10−6 M. Except for Ile-Ser-bradykinin and [Sar4]-bradykinin, none of the kinin analogs were more potent in this regard than bradykinin. Bacitracin, γ-aminobutyric acid, ε-aminocaproic acid, and structurally related compounds were also tested. The IC50 value for bacitracin was 1.9 ± 0.4 × 10−4 M, γ-aminobutyric acid, 83.4 ± 7.2 mM, and for ε-aminocaproic acid, 7.0 ± 1.4 mM. Compounds were also evaluated for their abilities to prevent 125I-labelled [Tyr1]-kallidin binding to angiotensin I converting enzyme inhibited by EDTA. The IC50 values for bradykinin, bacitracin, γ-aminobutyric acid, and ε-aminocaproic acid were 1.6 ± 0.3 × 10−8 M, 2.6 ± 0.9 × 10−6 M, >291 mM, and 13.2 ± 3.9 mM, respectively.