Thermodynamics of the interaction of benzodiazepines with human serum albumin

Janssen, Lambert H.M.; Dröge, J. H. M.; Durlinger, F.J.

doi:10.1016/0040-6031(90)80574-i

Cited by 8 publications

(5 citation statements)

References 10 publications

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“…This finding is consistent with earlier results showing that the basic conformation of HSA has a relatively stronger affinity for hydrophobic ligands, i.e. warfarin [14], diazepam [15,16] and bilirubin [17,18]. By measuring the binding constant of HSA for warfarin at varying pH Wilting et al .…”

Section: Discussionsupporting

confidence: 92%

Structural heterogeneity of the binding sites of HSA for phenyl‐groups and medium‐chain fatty acids

Lund

Bjerrum

1999

European Journal of Biochemistry

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A new facet of the very heterogeneous albumin molecule is described. Chromatography at pH 6±9 of human serum albumin (HSA) on a phenyl-sepharose column separates it into two nonconvertible conformations that are, in turn, in equilibrium with its binding and nonbinding forms. The hydrophobic interaction of HSA with phenyl-sepharose depends on ionic strength, pH, and time of contact with the immobilized ligand. Binding as a function of pH shows a minimum at pH 6.5, and the binding profile at pH 7±9 fits the titration of a weak monoprotic acid with a pK a of 7.3. There was no observable difference in the CD spectra or the masses of the two forms. The equilibrium between the albumin forms was examined under defined conditions and cannot be explained by a simple two-state model. Thus rechromatography of the nonbinding fraction derived from a sample in which 50% of the protein was originally retained resulted only in 10±20% bound protein. Correspondingly only 70±80% of the binding form was retained. A model explaining the observations can be derived if two species, I and II, exist in the solution, both being in an equilibrium with a binding and a nonbinding form, but in which I is not in equilibrium with II. The rate of conversion between the binding and nonbinding conformations was determined to be faster than 15 s at room temperature.

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Section: Discussionsupporting

confidence: 92%

Structural heterogeneity of the binding sites of HSA for phenyl‐groups and medium‐chain fatty acids

Lund

Bjerrum

1999

European Journal of Biochemistry

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“…Of these two components, the greatest contribution to the total change in free energy at 37 • C was the change in enthalpy. The decrease in entropy seen upon the binding of carbamazepine to HSA is somewhat unusual in that most drugs and small solutes show an increase in entropy when they bind to this protein [18,24,[40][41][42][43]. However, a decrease in entropy has been noted in some cases, such as in the binding of benzodiazepines or heptacarboxyl porphyrin to HSA [41].…”

Section: Thermodynamic Studiesmentioning

confidence: 90%

Chromatographic analysis of carbamazepine binding to human serum albumin

Kim

Hage

2005

Journal of Chromatography B

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“…The decrease in entropy seen upon the binding of carbamazepine to HSA is somewhat unusual in that most drugs show an increase in entropy when binding to this protein [38]. However, a decrease in entropy has been noted in some previous cases, such as binding of benzodiazepines or heptacarboxyl porphyrin to HSA [39][40][41].…”

Section: Thermodynamic Studiesmentioning

confidence: 97%