From the potent and selective mu opioid receptor agonist H-Dmt-D-Arg-Phe-Lys-NH2 to the potent delta antagonist H-Dmt-Tic-Phe-Lys(Z)-OH

H-Dmt-D-Arg-Phe-Lys-NH2 ([Dmt1]DALDA) binds with high affinity and selectivity to the í 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 í agonist into a potent and selective ä antagonist H-Dmt-Tic-Phe-Lys(Z)-OH. Such a ä antagonist could be used as a pharmacological tool.