Skip to main content

Thank you for visiting nature.com. 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.

Highly active cyclic and bicyclic somatostatin analogues of reduced ring size

Abstract

THE biological activity of an organic compound represents the sum of several properties, including solubility, absorption, transport, plasma protein binding, metabolism and receptor binding. The degree of molecular flexibility may affect these properties in different ways. Our approach to the design of somatostatin analogues with reduced susceptibility to metabolic inactivation has been both to eliminate those amino acids which are not required for biological activity and to increase the rigidity of the molecule. We report here the preparation of conformationally constrained analogues of somatostatin (Fig. 1, IIa and III) which are highly active inhibitors of the release of insulin, glucagon and growth hormone in vivo. Analogue III (Fig. 1), which retains only four of the amino acids of the natural hormone (sequence 7–10), is relatively resistant to the action of trypsin in vitro.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. Veber, D. F. et al. Proc. natn. Acad. Sci. U.S.A. 75, 2636–2640 (1979).

    Article  ADS  Google Scholar 

  2. Sarantakis, D., McKinley, W. A., Jaunakais, I., Clark, D. & Grant, N. H. Clin. Endocr. 5, 275–278S (1976).

    Article  Google Scholar 

  3. Rudinger, J. & Jost, K. Experientia 20, 570–571 (1964).

    Article  CAS  Google Scholar 

  4. Jost, K. & Rudinger, J. Colln Czech, chem. Commun. Engl. Edn 32, 1229–1241 (1967).

    Article  CAS  Google Scholar 

  5. Vale, W., Rivier, J., Ling, N. & Brown, M. Metabolism 27, Suppl. 1, 1391–1401 (1978).

    Article  CAS  Google Scholar 

  6. Arison, B. H., Hirschmann, R. & Veber, D. F. Bioorg. Chem. 7, 447–451 (1978).

    Article  CAS  Google Scholar 

  7. Rivier, J., Brown, M. & Vale, W. Biochem. biophys. Res. Commun. 65, 746–751 (1975).

    Article  CAS  Google Scholar 

  8. Torchiana, M. L., Cook, P. G., Weise, S. R., Saperstein, R. & Veber, D. F. Archs int. Pharmac. Ther. 235, 170–176 (1978).

    CAS  Google Scholar 

  9. Schonbrunn, A. & Tashjian, A. H. Jr J. biol. Chem. 253, 6473–6483 (1978).

    CAS  PubMed  Google Scholar 

  10. Craig, L. C., Hausmann, W. & Weisiger, J. R. J. Am. chem. Soc. 76, 2839 (1954).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

VEBER, D., HOLLY, F., NUTT, R. et al. Highly active cyclic and bicyclic somatostatin analogues of reduced ring size. Nature 280, 512–514 (1979). https://doi.org/10.1038/280512a0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/280512a0

This article is cited by

Comments

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.

Search

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