Stopped-flow studies on drug-protein binding |
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Authors: | N Rietbrock A Laßmann |
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Institution: | (1) Abteilung für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-6000 Frankfurt/Main, Federal Republic of Germany |
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Abstract: | Summary We have studied the binding of warfarin to human serum albumin (HSA) with the stopped-flow method. At 37°C the rate constant for the velocity of dissociation of the stable warfarin-HSA complex is 10s–1 (t
50%=0.07 s). Concentration and temperature dependent association constants for warfarin binding to HSA have been measured (2.5·105 M–1 s–1 at 6°C, 9.8·105 M–1 s–1 at 22°C and 15.3·105 M–1 s–1 at 37°C). Our experimentally obtained relaxation constants are best explained by the existence of 5 equivalent low affinity binding sites for warfarin on the HSA molecule, each capable of conversion into a high affinity site. The measured energy of activation for this conversion is 57.5 kJ M–1. |
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Keywords: | Protein binding-kinetics Warfarin Human Serum Albumin Stopped-flow Energy of activation |
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