Kinetics of the inhibition of human renin by an inhibitor containing a hydroxyethylene dipeptide isostere
- 1 December 1987
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 26 (24), 7621-7626
- https://doi.org/10.1021/bi00398a014
Abstract
We have studied the inhibition of both human and hog renins by compound 1 [Boc-Pro-Phe-N.alpha.-MeHis-Leu.psi.(CHOHCH2)Val-Ile-(aminomethyl)pyridine] using kinetics. The inhibition of human renin was shown to be time-dependent and followed a minimal two-step mechanism. A loosely bound EI complex was formed rapidly with a dissociation constant, K1, of 12 nM. A second EI complex was slowly formed and was found to be 64-fold more strongly bound with an overall KI* of 0.19 nM. The inhibition of human renin was shown to be competitive by both initial and final steady-state velocities. Compound 1 was also shown to be a competitive inhibitor of hog renin with a K1 of 12 nM, but no evidence for time-dependent inhibition was detected. The differences in overall KI and inhibition kinetics may be a consequence of the similarities in structure between 1 and human angiotensinogen.This publication has 5 references indexed in Scilit:
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