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

BALBONI, GIANFRANCO;COCCO M. T.;SALVADORI S.;ROMAGNOLI R.;SASAKI Y.;OKADA Y.;BRYANT S. D.;JINSMAA Y.;LAZARUS L. H.

2005-01-01

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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.