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.
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.
Balboni
Gianfranco
G
Department of Toxicology, University of Cagliari, I-09124, Cagliari, Italy. gbalboni@unica.it
Cocco
Maria Teresa
MT
Salvadori
Severo
S
Romagnoli
Romeo
R
Sasaki
Yusuke
Y
Okada
Yoshio
Y
Bryant
Sharon D
SD
Jinsmaa
Yunden
Y
Lazarus
Lawrence H
LH
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
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