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Design of angiotensin converting enzyme inhibitors

Nature Medicine volume 5, pages 1110–1112 (1999)Cite this article

Specific inhibitors of angiotensin-converting enzyme, known to the lay public as ACE inhibitors, have now been embraced by the medical community as first-line therapy for hypertensive disease and congestive heart failure. However, it is important for historical and scientific perspective to note that in the late 1960s, the so-called renin–angiotensin system, of which ACE is a component, was a poorly understood enzyme system that was not widely accepted as being important for blood pressure regulation. Renin was discovered in the late 19th century as a hypertensive substance in blood, and was shown in 1934 to be an enzyme that was elevated in the blood of renal hypertensive rats1. The potent blood pressure-elevating octapeptide angiotensin II, produced in blood by the action of renin, was isolated in the late 1930s (ref. 2). But ACE, which cleaves a His–Leu dipeptide from the inactive decapeptide renin product angiotensin I to form angiotensin II, was not identified until 1954 (ref. 3).

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu Angiotensin I

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Figure 1: The known active site of carboxypeptidase A and a hypothetical model of the active site of ACE.
Figure 2

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  1. 20 Lake Shore Drive, West Windsor , 08550, NJ

    David W. Cushman

  2. 79 Hemlock Circle, Princeton, 08540, NJ

    Miguel A. Ondetti

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Cushman, D., Ondetti, M. Design of angiotensin converting enzyme inhibitors. Nat Med 5, 1110–1112 (1999). https://doi.org/10.1038/13423

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