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Science 22 April 1977:
Vol. 196. no. 4288, pp. 441 - 444
DOI: 10.1126/science.191908
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Articles

Science, Vol 196, Issue 4288, 441-444
Copyright © 1977 by American Association for the Advancement of Science

articles

Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents

MA Ondetti, B Rubin, and DW Cushman

A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, has enabled us to design a new class of potent and specific inhibitors. These compounds, carboxyalkanoyl and mercaptoalkanoyl derivatives of proline, inhibit the contractile response of guinea pig ileal strip to angiotensin I and augment its response to bradykinin. When administered orally to rats, these agents inhibit the pressor effect of angiotensin I, augment the vasodepressor effect of bradykinin, and lower blood pressure in a model of renovascular hypertension.


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