TYROSINE-IODINATION CONVERTS THE DELTA-OPIOID PEPTIDE ANTAGONIST TIPPTO AN AGONIST

The binding properties and pharmacological activities of H-Tyr(3'-I)-T ic-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 d isplacement curve of [H-3]diprenorphine binding by [Tyr(3'-I)(1)]TIPP was shifted to the right in the presence of Na+ and 5'-guanylylimidodi phosphate, 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 d eferens assay and its effect was both naloxone- and TIPP-reversible, T hese data show that monoiodination at the 3'-position of the N-termina l tyrosine aromatic ring of TIPP converted it from a potent and select ive antagonist to a full agonist at delta-opioid receptors.