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A new class of angiotensin-converting enzyme inhibitors

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Abstract

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.

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References

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

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

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

    Article  CAS  Google Scholar 

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

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

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

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

Download references

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Patchett, A., Harris, E., Tristram, E. et al. A new class of angiotensin-converting enzyme inhibitors. Nature 288, 280–283 (1980). https://doi.org/10.1038/288280a0

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