title: From the potent and selective mu opioid receptor agonist H-Dmt-d-Arg-Phe-Lys-NH(2) to the potent delta antagonist H-Dmt-Tic-Phe-Lys(Z)-OH.
abstract: H-Dmt-d-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA) binds with high affinity and selectivity to the mu opioid receptor and is a potent and long-acting analgesic. Substitution of d-Arg in position 2 with Tic and masking of the lysine amine side chain by Z protection and of the C-terminal carboxylic function instead of the amide function transform a potent and selective mu agonist into a potent and selective delta antagonist H-Dmt-Tic-Phe-Lys(Z)-OH. Such a delta antagonist could be used as a pharmacological tool.
authors.affiliation: Department of Toxicology, University of Cagliari, I-09124, Cagliari, Italy. gbalboni@unica.it
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Balboni
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Cocco
authors.forename: Severo
authors.initials: S
authors.lastname: Salvadori
authors.forename: Romeo
authors.initials: R
authors.lastname: Romagnoli
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Okada
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Bryant
authors.forename: Yunden
authors.initials: Y
authors.lastname: Jinsmaa
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Lazarus
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013574:Synaptosomes / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
chemical_list: C504527:2',6'-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinolinecarbonyl-phenylalanyl-(N(epsilon)-benzyloxycarbonyl)lysine; C424424:2',6'-dimethyltyrosyl-arginyl-phenylalanyl-lysinamide; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu