THERMODYNAMICS OF LIGAND-BINDING TO THE CLONED DELTA-OPIOID RECEPTOR

The goal of this study was to determine the relative contribution of e ntropy and enthalpy to the free energies of binding to recombinant mou se delta-opioid receptors for the peptide agonist, DPDPE ([D-Pen(2),D- Pen(5)]enkephalin), the peptide antagonist, TIPP(Psi) (Tyr-Tic Psi[CH2 NH]Phe-Phe-OH), the nonpeptide agonist, SNC80 ((+)-4-[(alpha ipeazinyl )-3-methoxybenzyl]-N,N-diethylbenzamide), and the nonpeptide antagonis t, naltrindole. Competitive binding studies were carried out using [H- 3]naltrindole at 0 degrees C, 12 degrees C, 25 degrees C and 37 degree s C, the affinities calculated and van't Hoff plots constructed for ea ch ligand. The temperature dependence of binding and van't Hoff plots indicated that the entropy contribution is the major component of the free energy, for all four ligands, independent of its activity or chem ical nature.