albumin - publications

1. Eur J Pharm Sci. 2012 Mar 29. [Epub ahead of print]

Insights into the binding of the drugs diclofenac sodium and cefotaxime sodium to
serum albumin: Calorimetry and spectroscopy.

Sharma R, Choudhary S, Kishore N.

Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400
076, India.

Understanding physical chemistry underlying drug-protein interactions is
essential to devise guidelines for the synthesis of target oriented drugs.
Binding of a non-steroidal anti-inflammatory drug, diclofenac sodium (DCF) and an
antibiotic drug, cefotaxime sodium (CFT) belonging to the family of
cephalosporins with bovine serum albumin (BSA) has been examined using a
combination of isothermal titration calorimetry (ITC), differential scanning
calorimetry (DSC), steady state and time resolved fluorescence and circular
dichroism spectroscopies. Binding affinity of both DCF and CFT with BSA is
observed to be of the order of 10(4)M(-1), with the binding profiles fitting well
to the single set of binding site model. The disagreement between calorimetric
and van't Hoff enthalpies indicates non-adherence to a two-state binding process
which could be attributed to changes in the conformation of the protein upon
ligand binding as well as with increase in the temperature. Circular dichroism
and the fluorescence results, however, do not show any major conformational
changes upon binding of these drugs to BSA, and hence the discrepancy could be
due to temperature induced conformational changes in the protein. The results of
ionic strength dependence and binding in the presence of anionic, cationic and
non-ionic surfactants indicate, involvement of more that a single type of
interaction in the binding process. The ITC results for the binding of these
drugs to BSA in presence of each other indicate that the binding sites for the
two drugs are different, and therefore binding of one is not influenced by the
other. The DSC results provide quantitative information on the effect of these
drugs on the stability of serum albumin. The combined calorimetric and
spectroscopic approach has provided a detailed analysis including thermodynamics
of the binding of DCF and CFT with BSA qualitatively and quantitatively.

Copyright © 2012 Elsevier B.V. All rights reserved.

PMID: 22483968 [PubMed - as supplied by publisher]