Preparation and binding properties of radioiodinated analogues of dermorphin and deltorphin with high specificity for the mu- and delta-opioid receptors.

The synthesis, purification, chemical characterization, and binding properties of two 125I-labeled analogues of dermorphin and deltorphin-I are described. Native deltorphin-I and [Lys7] dermorphin sequences were elongated by an aminopentyl chain on their C-terminal amide function and alkylated with the 125I-labeled monoiodinated derivative of Bolton-Hunter reagent (BH*). The resulting radiolabeled peptides, epsilon-BH* [Lys7] dermorphin 5-aminopentylamide and omega-BH* deltorphin-I 5-aminopentylamide, have kept most of the original properties of the parent peptides. They bind with high selectivity and specificity to the mu- (dermorphin analogue) or delta- (deltorphin-I analogue) opioid receptors from rat brain or from cells transfected with cDNAs encoding the mu and delta receptors. The autoradiographic distribution of specific binding sites for the 125I-labeled dermorphin and deltorphin-I analogues in rat brain is in complete agreement with previously reported localizations of mu- and delta-opioid receptors. The two radiolabeled peptides are the best ligands of mu- and delta-opioid receptors currently available in terms of sensitivity, specificity, and selectivity.