TYROSINE-IODINATION CONVERTS THE DELTA-OPIOID PEPTIDE ANTAGONIST TIPP TO AN AGONIST

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 delta-opioid receptor antagonist H-Tyr-Tic-Phe-Phe-OH (TIPP), [Tyr(3'-I)(1)]TIPP is a selective and potent ligand at delta-opioid receptors. The displacement curve of [H-3]diprenorphine binding by [Tyr(3'-I)(1)]TIPP was shifted to the right in the presence of Na+ and 5'-guanylylimidodiphosphate, suggesting that it acted as a delta-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 delta-opioid receptors.