Thermodynamics of ligand binding to the cloned δ-opioid receptor

Abstract The goal of this study was to determine the relative contribution of entropy and enthalpy to the free energies of binding to recombinant mouse δ-opioid receptors for the peptide agonist, DPDPE ([ d -Pen 2 , d -Pen 5 ]enkephalin), the peptide antagonist, TIPP(ψ) (Tyr-Ticψ[CH 2 NH]Phe-Phe-OH), the nonpeptide agonist, SNC80 ((+)-4-[(α R )-α-((2 S ,5 R )-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]- N,N -diethylbenzamide), and the nonpeptide antagonist, naltrindole. Competitive binding studies were carried out using [ 3 H]naltrindole at 0°C, 12°C, 25°C and 37°C, the affinities calculated and van't Hoff plots constructed for each 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 chemical nature.

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