CYCLIC ENKEPHALIN ANALOGS WITH EXCEPTIONAL POTENCY AND SELECTIVITY FOR DELTA-OPIOID RECEPTORS

Superpotent and highly delta-opioid receptor selective cyclic peptides of the general formula H-Tyr-c[D-Pen-Gly-Phe(p-X)-Pen]-Phe-OH (where X = hydrogen or halogen) have been synthesized. In the binding assays the most selective and most potent compound is the p-bromophenylalanin e-4 analogue (IC50 value = 0.19 nM, selectivity ratio = 21 000 for del ta vs mu). In the GPI and MVD bioassays the most selective and most po tent analogue is the p-fluoro-substituted analogue Tyr-[D-Pen-Gly-Phe( p-F)-Pen]-Phe-OH. In the MVD assay it has an exceptionally low IC50 va lue of 0.016 nM and a delta vs mu selectivity ratio of 45 000.