The Relationship Between Structure and Activity Among Opioid Peptides |
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Authors: | Jeffrey R. Deschamps Clifford George Judith L. Flippen-Anderson |
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Affiliation: | (1) Laboratory for the Structure of Matter, Code 6030, Naval Research Laboratory, Washington, DC, 20375, U.S.A. |
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Abstract: | 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 -bend. More recent reports include a third conformation for Leu-enkephalin and constrained opioid peptides from two new classes (i.e. cyclic and all-aromatic 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. |
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Keywords: | enkephalin neuropeptide pharmacophore X-ray diffraction |
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