Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A new class of angiotensin-converting enzyme inhibitors


Much current attention focuses on the renin–angiotensin system in relation to mechanisms controlling blood pressure and renal function. Recent demonstrations (ref 1, ref. 2 and refs therein) that angiotensin-converting enzyme inhibitors show promising clinical antihypertensive properties have been of particular interest. We now report on the design of a novel series of substituted N-carboxymethyl-dipeptides which are active in inhibiting angiotensin-converting enzyme at nanomolar levels. We suggest that these compounds are transition-state inhibitors and that extensions of this design to other metalloendopeptidases merit further study.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Gavras, H. et al. New Engl. J. Med. 291, 817–821 (1974).

    CAS  Article  Google Scholar 

  2. 2

    Atkinson, A. B. & Robertson, J. I. S. Lancet ii, 836–839 (1979).

    Article  Google Scholar 

  3. 3

    Skeggs, L. T., Marsh, W. H., Kahn, J. R. & Shumway, N. P. J. exp. Med. 99, 275–282 (1954).

    CAS  Article  Google Scholar 

  4. 4

    Yang, H. Y. T., Erdös, E. G. & Levin, Y. Biochim. biophys. Acta 214, 374–376 (1970).

    CAS  Article  Google Scholar 

  5. 5

    Ondetti, M. A., Rubin, B. & Cushman, D. W. Science 196, 441–444 (1977).

    ADS  CAS  Article  Google Scholar 

  6. 6

    Cushman, D. W., Cheung, H. S., Sabo, E. F. & Ondetti, M. A. Biochemistry 16, 5484–5491 (1977).

    CAS  Article  Google Scholar 

  7. 7

    Levine, W. G. in The Pharmacological Basis of Therapeutics 5th edn (eds Goodman, L. S. & Gilman, A.) 919–920 (Macmillan, New York, 1975).

    Google Scholar 

  8. 8

    Cushman, D. W., Cheung, H. S., Sabo, E. F. & Ondetti, M. A. Fedn Proc. 33, 2778–2782 (1979).

    Google Scholar 

  9. 9

    Soffer, R. L. A. Rev. Biochem. 45, 73–94 (1976).

    CAS  Article  Google Scholar 

  10. 10

    Cheung, H. S., Wang, F. L., Ondetti, M. A., Sabo, E. F. & Cushman, D. W. J. biol. Chem. 255, 401–407 (1980).

    CAS  PubMed  Google Scholar 

  11. 11

    Beckner, C. F. & Caprioli, R. M. Biochem. biophys. Res. Commun. 93, 1290–1296 (1980).

    CAS  Article  Google Scholar 

  12. 12

    Stability Constants of Metal Ion Complexes 520 (Spec. Publ. no. 17, The Chemical Society, London, 1964).

  13. 13

    Wolfenden, R. A Rev. Biophys. Bioengng 5, 271–306 (1976).

    CAS  Article  Google Scholar 

  14. 14

    Sweet, C. S. et al. J. Pharmac. exp. Ther. (submitted).

  15. 15

    Gross, D. M. et al. J. Pharmac. exp. Ther. (submitted).

  16. 16

    Biollaz, J. et al. Clin. Pharmac. Ther. (submitted).

  17. 17

    Dorer, F. E., Kahn, J. R., Lentz, K. E., Levine, M. & Skeggs, L. T. Circulation Res. 34, 824–827 (1974).

    CAS  Article  Google Scholar 

  18. 18

    Piquilloud, Y., Reinharz, A. & Roth, M. Biochim. biophys. Acta 206, 136–142 (1970).

    CAS  Article  Google Scholar 

  19. 19

    Allinger, N. L. J. Am. chem. Soc. 81, 232 (1959).

    CAS  Article  Google Scholar 

  20. 20

    Rubin, B. et al. J. Pharmac. exp. Ther. 204, 271 (1978).

    CAS  Google Scholar 

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

Patchett, A., Harris, E., Tristram, E. et al. A new class of angiotensin-converting enzyme inhibitors. Nature 288, 280–283 (1980).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing