Synthesis of [ [formula omitted]-ALA 2, 4′- 125I-PHE 3, GLU 4] deltorphin and characterization of its δ opioid receptor binding properties

Abstract

Both [ d -Ala 2, Glu 4]Deltorphin and [ d -Ala 2, 4′-I-Phe 3, Glu 4]Deltorphin are highly selective ligands for δ, relative to μ, opioid receptors. Radiolabeled [ d -Ala 2, 4′- 125I-Phe 3, Glu 4]Deltorphin ([ 125I]Deltorphin) was prepared with a specific activity of 2200 Ci/mmol from [ d -Ala 2, 4′-NH 2-Phe 3, Glu 4]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.