Effect of New Peptide Inhibitors on the Ratio of Angiotensin I-Converting and Kinin-Degrading Activity of Dipeptidyl Carboxypeptidase (Angiotensin-Converting Enzyme)

E. V. Kalinina,¹ V. F. Posdnev,¹ N. V. Komissarova,¹ and O. A. Gomazkov^1,2

¹Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya ul. 10, Moscow, 119832 Russia; fax: (7-095) 245-08-57.

²To whom correspondence should be addressed.

Submitted April 2, 1996; revision submitted December 16, 1996.

The effect of N^alpha-carboxyalkylated dipeptides on angiotensin-converting and kinin-degrading activity of angiotensin-converting enzyme (ACE, dipeptidyl carboxypeptidase) was studied. These inhibitors selectively affected ACE-induced hydrolysis of angiotensin I-like and bradykinin-like (hippuryl-His-Leu and hippuryl-Phe-Arg, respectively) substrates in microsomal fractions of rat lungs and kidneys and rat blood serum. The inhibition constants of both types of activity were determined for these enzyme preparations and also for ACE from porcine seminal fluid and highly purified ACE from porcine lung. In all cases high inhibition selectivity of angiotensin-generating and kininase activities of ACE was found.

KEY WORDS: angiotensin-converting enzyme, kininase II, bradykinin, inhibitors.

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