Structural basis for bifunctional peptide recognition at human δ-opioid receptor
G Fenalti, NA Zatsepin, C Betti, P Giguere… - Nature structural & …, 2015 - nature.com
Nature structural & molecular biology, 2015•nature.com
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 …
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 …
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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