EXCLUSIVE AFFINITY-LABELING OF MU-OPIOID RECEPTORS BY MORPHICEPTIN ANALOGS CONTAINING S-(3-NITRO-2-PYRIDYLTHIO)CYSTEINE

The S-(3-nitro-2-pyridylthio) (Npys) group only reacts with a free mer capto group to form a disulfide bond. A series of morphiceptin analogs containing SNpys-cysteine were designed and synthesized for specific affinity-labeling of mu opioid receptors. Affinity-labeling of opioid receptors was monitored and evaluated by radioligand receptor binding assays using rat brain membranes and specific tritium-labeled ligands of enkephalin analogs. It was found that analogs with Cys(Npys) at pos ition 4 or 5 bind covalently to mu receptors, but not to delta recepto rs, resulting in a discriminative and exclusive affinity labeling of m u opioid receptor subtype.