| Abstract
| - Drug−receptor binding thermodynamics has proved to be a valid tool for pharmacological andpharmaceutical 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 agonistsand antagonists by thermodynamic methods. Since a single thermodynamic study oncytoplasmic 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. Thebinding at 25 °C appears enthalpy/entropy-driven (−53.0 ≤ ΔG° ≤ −48.6, −34.5 ≤ ΔH°≤ −19.9kJ/mol, 0.057 ≤ ΔS° ≤ 0.111, and −2.4 ≤ ΔCp° ≤ −1.7 kJ mol-1 K-1) and is interpreted interms of hydrophobic and hydrogen-bonded specific interactions. Results obtained for cytoplasmic receptors are extensively compared with those known for typical membrane receptors,in particular the adenosine A1 receptor, to investigate the thermodynamic bases of drug−receptor binding from the most general point of view.
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