From the Potent and Selective μ Opioid Receptor Agonist H-Dmt-d-Arg-Phe-Lys-NH2 to the Potent δ 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.