Binding thermodynamics as a tool to investigate the mechanisms of drug-receptor interactions: thermodynamics of cytoplasmic steroid/nuclear receptors in comparison with membrane receptors.

Drug-receptor binding thermodynamics has proved to be a valid tool for pharmacological and pharmaceutical characterization of molecular mechanisms of receptor-recognition phenomena. The large number of membrane receptors so far studied has led to the discovery of enthalpy-entropy compensation effects in drug-receptor binding and discrimination between agonists and antagonists by thermodynamic methods. Since a single thermodynamic study on cytoplasmic receptors was known, this paper reports on binding thermodynamics of estradiol, ORG2058, and R1881 bound to estrogen, progesterone, and androgen steroid/nuclear receptors, respectively, as determined by variable-temperature binding constant measurements. The binding at 25 degrees C appears enthalpy/entropy-driven (-53.0