Letters in Peptide Science

, Volume 5, Issue 5–6, pp 337–340 | Cite as

The relationship between structure and activity among opioid peptides

  • Jeffrey R. Deschamps
  • Clifford George
  • Judith L. Flippen-Anderson
Article
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Summary

Since the discovery and isolation of the endogenous opioid peptides Leu- and Met-enkephalin, structural studies have been focused on deducing the bioactive conformation of the peptide ligands. Theoretically, linear peptides can have many different backbone conformations, yet early, X-ray studies on enkephalin and its analogues showed only two different backbone conformations: extended and single β-bend. More recent reports include a third conformation for Leu-enkephalin and constrained opioid peptides from two ‘new’ classes (i.e. cyclic and ‘allaromatic’ peptides). In this report the relationship between solid-state X-ray structure and opioid peptide activity is examined. The N-terminal amine nitrogen and the two aromatic rings have previously been identified as structural features important to the biological activity of opioid peptides. From X-ray studies we find that the distances between the centroids of the aromatic rings, and between the N-terminal amine nitrogen and the centroid of the phenylalanine ring, vary over a large range. There is a discernible relationship, however, between the separation of the two rings and their orientation that correlates with activity.

Key words

enkephalin neuropeptide pharmacophore X-ray diffraction 
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Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Jeffrey R. Deschamps
    • 1
  • Clifford George
    • 1
  • Judith L. Flippen-Anderson
    • 1
  1. 1.Laboratory for the Structure of MatterNaval Research LaboratoryWashington, DCU.S.A.

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