PREPARATION AND BINDING-PROPERTIES OF RADIOIODINATED ANALOGS OF DERMORPHIN AND DELTORPHIN WITH HIGH SPECIFICITY FOR THE MU-OPIOID AND DELTA-OPIOID RECEPTORS

The synthesis, purification, chemical characterization, and binding pr operties of two I-125-labeled analogues of dermorphin and deltorphin-I are described, Native deltorphin-I and [Lys(7)]dermorphin sequences w ere elongated by an aminopentyl chain on their C-terminal amide functi on and alkylated with the I-125-labeled monoiodinated derivative of Bo lton - Hunter reagent (BH). The resulting radiolabeled peptides, epsi lon-BH [Lys(7)] dermorphin 5-aminopentylamide and omega-BH* deltorphi n-I 5-aminopentylamide, have kept most of the original properties of t he parent peptides. They bind with high selectivity and specificity to the mu- (dermorphin analogue) or delta- (deltorphin-I analogue) opioi d receptors from rat brain or from cells transfected with cDNAs encodi ng the mu and delta receptors, The autoradiographic distribution of sp ecific binding sites for the I-125-labeled dermorphin and deltorphin-I analogues in rat brain is in complete agreement with previously repor ted localizations of mu- and delta-opioid receptors, The two radiolabe led peptides are the best ligands of mu- and delta-opioid receptors cu rrently available in terms of sensitivity, specificity, and selectivit y.