Opioid infidelity: novel opioid peptides with dual high affinity for delta- and mu-receptors.
Deltorphins represent the paragon of delta-opioid-receptor ligands of natural origin, since they exceed the affinity and selectivity of the endogenous enkephalins by orders of magnitude. A series of opioid peptides have been developed in which the change in a single amino acid causes an extraordinary increase in mu-receptor binding while maintaining high affinity for the delta-receptor. The peptides appear to have a similar extended conformation in solution with a type-I beta-turn in the N-terminus region, suggesting that tertiary architecture plays a pivotal role in enabling the peptide to bind indiscriminately to mu- and delta-receptors. These dual-affinity peptide ligands can serve to mask delta- and mu-receptors while mapping kappa-receptors in the nervous system, to provide an understanding of the differences and similarities in the structure of the binding domains of delta- and mu-receptors, and might lead to a comprehensive new regime for the clinical management of acute and chronic pain.
Lazarus
L H
LH
Peptide Neurochemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Bryant
S D
SD
Salvadori
S
S
Attila
M
M
Sargent Jones
L
L
D001667:Binding, Competitive; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects*
D009842:Oligopeptides; D018847:Opioid Peptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C059567:deltorphin