TIPP[PSI], A HIGHLY SELECTIVE DELTA-LIGAND

TIPP[Psi] is a new delta-selective opioid peptide antagonist. In the current study, we have explored its selectivity against the mu and kappa receptor subtypes. Against [H-3]DPDPE binding, TIPP[Psi] is quite potent, with a K-1 value of <1 nM, confirming its potent activity at delta receptors. In contrast, its K-1 values against mu(1), mu(2), kappa(1), kappa(2) and kappa(3) binding sites are all >5 mu M. DPDPE also is delta-selective. It labels delta sites > 25-fold more potently than mu(1) receptors and is even more selective against the other subtypes. However, this selectivity does not compare to the delta/mu(1) selectivity of TIPP[Psi] which exceeds 15,000. This far higher selectivity, coupled with its antagonist properties, gives TIPP[Psi] a number of advantages over previously reported delta-selective compounds. We have utilized these advantages to develop an improved mu(1) binding assay using TIPP[Psi].