Tyrosine-iodination converts the δ-opioid peptide antagonist TIPP to an agonist

Abstract The binding properties and pharmacological activities of H-Tyr(3′-I)-Tic-Phe-Phe-OH ([Tyr(3′-I) 1 ]TIPP) were studied. Similar to the δ-opioid receptor antagonist H-Tyr-Tic-Phe-Phe-OH (TIPP), [Tyr(3′-I) 1 ]TIPP is a selective and potent ligand at δ-opioid receptors. The displacement curve of [ 3 H]diprenorphine binding by [Tyr(3′-I) 1 ]TIPP was shifted to the right in the presence of Na + and 5t'-guanylylimidodiphosphate, suggesting that it acted as a δ-opioid receptor agonist. [Tyr(3′-I) 1 ]TIPP also behaved as a full agonist in the mouse vas deferens assay and its effect was both naloxone- and TIPP-reversible. These data show that monoiodination at the 3′-position of the N-terminal tyrosine aromatic ring of TIPP converted it from a potent and selective antagonist to a full agonist at δ-opioid receptors.