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Calorimetric and spectroscopic studies on the interaction of anticancer drug mitoxantrone with human serum albumin

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Title Calorimetric and spectroscopic studies on the interaction of anticancer drug mitoxantrone with human serum albumin
 
Creator KESWANI, N
KISHORE, N
 
Subject PLASMA-PROTEIN BINDING
MASS-SPECTROMETRY
CHROMATOGRAPHY
ULTRAFILTRATION
ACID
Human serum albumin
Mitoxantrone
Isothermal titration calorimetry
Drug-protein interactions
Thermodynamics
Spectroscopy
 
Description Binding of the anticancer drug mitoxantrone with the protein human serum albumin (HSA) has been studied by using isothermal titration calorimetry (ITC), in combination with fluorescence, UV-visible, and circular dichroism spectroscopy. The thermodynamic parameters of binding have been evaluated from ITC and spectroscopic results and compared. The ITC results demonstrate that the binding of mitoxantrone with HSA occurs according to two sets of binding sites on the protein as opposed to the fluorescence and UV-visible spectroscopic results. Blockage of one binding site on HSA for mitoxantrone in the presence of NaCl indicates strong involvement of electrostatic interactions in the binding of the drug with the protein. An insignificant temperature dependence of the association constant observed in fluorescence measurements suggests a very low enthalpy of binding which is in close agreement with the results obtained from ITC measurements. Fluorescence life time measurements suggest formation of a static complex between mitoxantrone and HSA. The discrepancies in the ITC and fluorescence results suggest that one of the binding sites on the protein for mitoxantrone does not contain tryptophan residue in its immediate vicinity. The calorimetric and spectroscopic results have provided quantitative information on the binding of mitoxantrone with HSA and suggest that the binding is dominated by electrostatic interactions. (C) 2011 Elsevier Ltd. All rights reserved.
 
Publisher ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
 
Date 2012-06-26T07:13:02Z
2012-06-26T07:13:02Z
2011
 
Type Article
 
Identifier JOURNAL OF CHEMICAL THERMODYNAMICS,43(9)1406-1413
0021-9614
http://dx.doi.org/10.1016/j.jct.2011.04.003
http://dspace.library.iitb.ac.in/jspui/handle/100/14105
 
Language English