RESUMO
In a previous paper (C. André et al., submitted to J. Chromatogr. B) a mathematical model based on the Langmuir theory was developed to visualize the competition effect between testosterone and deshydroepiandrosterone (DHEA) for their identical human serum albumin (HSA) binding cavity. In this work, the thermodynamic mechanisms of (i) the binding of two hormones, DHEA and testosterone to HSA and (ii) the testosterone displacement of its HSA binding cavity by DHEA was studied by biochromatography. The Na+ cation effect used as physico-chemical marker of these binding processes was clearly described. The Gibbs free energy value (DeltaGo ) of the displacement equilibrium was always negative demonstrating that DHEA well displaced testosterone of its HSA binding cavity. The thermodynamic data also showed that this displacement equilibrium was enthalpically controlled. Moreover, the effect of (Mg2+) concentration (x') on the two binding mechanisms was analyzed. It appeared that for old men with a deficit of testosterone, Mg(2+) supplementation during treatment with DHEA can increased the free testosterone concentration and its biological effect. All these results must be confirmed by in vivo test.
Assuntos
Desidroepiandrosterona/farmacocinética , Sais/química , Albumina Sérica/farmacocinética , Testosterona/farmacocinética , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/métodos , Desidroepiandrosterona/química , Humanos , Magnésio/química , Ligação Proteica/fisiologia , Albumina Sérica/química , Sódio/química , Testosterona/química , TermodinâmicaRESUMO
The mechanism of the binding of D,L dansyl amino acids to teicoplanin was investigated. Na+ was used as an indicator of the interactions between the solutes and teicoplanin. The number (n) of sodium ions, Na+, excluded from the solute-teicoplanin interface when analyte transfer occurred was determined. A thermodynamic study and enthalpy-entropy compensation were performed to further explore the interaction mechanism. From these results, it was shown that teicoplanin was balanced between 2 conformational states characterized by distinct enantioselective properties. This approach indicates that liquid chromatography (LC) is a useful tool to extract physicochemical and molecular information from retention data. Thus, LC can be used as a complementary technique with the conventional techniques of molecular interaction analysis.