Letter | Published:

Synthesis and conformations of hypothalamic hormone releasing factors: two QRF-analogues containing backbone N-methyl groups

Naturevolume 256pages750751 (1975) | Download Citation

Subjects

  • An Erratum to this article was published on 25 September 1975
  • An Erratum to this article was published on 09 October 1975

Abstract

SINCE its isolation and characterisation1,2, the hypothalamic hormone-releasing factor TRF (pGlu–His–Pro–NH2) has been the subject of several conformational studies. Most investigations have indicated that the steric characteristics of the three adjacent rings strongly limit the backbone conformational flexibility and support a preference for an extended structure. The importance of each functional group in the molecule in terms of biological potency has been systematically investigated (for review, see ref. 3). With one exception (methylation of the histidyl side chain in the Nτ position) all the chemical modifications which have been made to date were accompanied by a substantial loss of biological activity. We have shown4 that most of these modifications do not significantly affect the preferred backbone conformation of the hormone, emphasising the critical role of each functional group in TRF for optimal binding to the receptor sites.

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References

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    Burgus, R., Dunn, T. F., Desiderio, D., Ward, D., Vale, W., and Guillemin, R., Nature, 226, 321–325 (1970).

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    Vale, W., Grant, G., and Guillemin, R., in Frontiers in Neuroendocrinology (edit. by Ganong, W. F., and Martini, L.), 11 (Oxford University Press, New York and London, 1973).

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Author information

Affiliations

  1. Department of Chemistry, University of California, San Diego, La Jolla, California, 92037

    • B. DONZEL
    •  & M. GOODMAN
  2. The Salk Institute for Biological Studies, La Jolla, California, 92037

    • J. RIVIER
    • , N. LING
    •  & W. VALE

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https://doi.org/10.1038/256750a0

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