Abstract
Bifunctional μ- and δ-opioid receptor (OR) ligands are potential therapeutic alternatives, with diminished side effects, to alkaloid opiate analgesics. We solved the structure of human δ-OR bound to the bifunctional δ-OR antagonist and μ-OR agonist tetrapeptide H-Dmt-Tic-Phe-Phe-NH2 (DIPP-NH2) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt and Tic. The observed receptor-peptide interactions are critical for understanding of the pharmacological profiles of opioid peptides and for development of improved analgesics.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Binding Sites
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Crystallography, X-Ray
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HEK293 Cells
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Humans
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Models, Molecular
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Oligopeptides / chemistry
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Protein Structure, Tertiary
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Receptors, Opioid, delta / antagonists & inhibitors
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Receptors, Opioid, delta / chemistry*
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Tetrahydroisoquinolines / chemistry
Substances
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2',6'-dimethyltyrosyl-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalaninamide
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Oligopeptides
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Receptors, Opioid, delta
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Tetrahydroisoquinolines