Synthesis of [d-ALA², 4′-¹²⁵I-PHE³, GLU⁴] deltorphin and characterization of its δ opioid receptor binding properties

Both [d-Ala², Glu⁴]Deltorphin and [d-Ala², 4′-I-Phe³, Glu⁴]Deltorphin are highly selective ligands for δ, relative to μ, opioid receptors. Radiolabeled [d-Ala², 4′-¹²⁵I-Phe³, Glu⁴]Deltorphin ([¹²⁵I]Deltorphin) was prepared with a specific activity of 2200 Ci/mmol from [d-Ala², 4′-NH₂-Phe³, Glu⁴]Deltorphin through a diazonium salt intermediate. The inhibition of [¹²⁵I]Deltorphin binding to rat brain membranes by ligands selective for μ, δ, and κ opioid receptors is consistent with binding by the radioligand to a single site having the properties of a δ opioid receptor. The results of these studies are in good agreement with those obtained by structurally different δ opioid receptor ligands. The similarity between the δ receptor site labeled by [¹²⁵I]Deltorphin and those labeled by other δ receptor agonists, in contrast to differences seen by in vivo studies of their analgesic effects, is discussed.