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Structural basis for bifunctional peptide recognition at human δ-opioid receptor
Gustavo Fenalti1, Nadia A Zatsepin2, Cecilia Betti3
1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
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.
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