On the fundamental difference in the thermodynamics of agonist and antagonist interactions with β-adrenergic receptors and the mechanism of entropy-driven binding

Several investigations point to a fundamental difference between the molecular interactions of agonists and antagonists with the beta -adrenergic receptor. Whereas beta -agonists bind with large decreases in enthalpy and entropy, the binding of beta -antagonists is characterized by a small change of...

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Veröffentlicht in:Biochemical pharmacology 1990-08, Vol.40 (4), p.663-669
Hauptverfasser: Miklavc, Adolf, Kocjan, Darko, Mavri, Jonez, Koller, Jože, Hadži, Dušan
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Sprache:eng
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Zusammenfassung:Several investigations point to a fundamental difference between the molecular interactions of agonists and antagonists with the beta -adrenergic receptor. Whereas beta -agonists bind with large decreases in enthalpy and entropy, the binding of beta -antagonists is characterized by a small change of enthalpy and a large increase in entropy. Moreover, the difference in binding is reflected in the temperature dependence of the affinities. Agonists display large increases in affinity with temperature decreases, whereas the affinities of antagonists change little. The negative entropy change in agonist binding is usually ascribed to a supposed conformational change of the receptor. The increase of entropy in antagonist binding is assumed to be due to a hydrophobic binding mechanism. In this commentary, after a review of the experimental results, we critically assess the current interpretation, giving reasons as to why it may not be correct, and propose an alternative interpretation of the thermodynamic data in question, including the temperature dependence.
ISSN:0006-2952
1873-2968
DOI:10.1016/0006-2952(90)90299-Z