albumin - publications
Predict more albumin - ligand interactions now!
1. Eur J Pharm Sci. 2012 Mar 29. [Epub ahead of print]Insights into the binding of the drugs diclofenac sodium and cefotaxime sodium toserum albumin: Calorimetry and spectroscopy.Sharma R, Choudhary S, Kishore N.Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.Understanding physical chemistry underlying drug-protein interactions isessential to devise guidelines for the synthesis of target oriented drugs.Binding of a non-steroidal anti-inflammatory drug, diclofenac sodium (DCF) and anantibiotic drug, cefotaxime sodium (CFT) belonging to the family ofcephalosporins with bovine serum albumin (BSA) has been examined using acombination of isothermal titration calorimetry (ITC), differential scanningcalorimetry (DSC), steady state and time resolved fluorescence and circulardichroism spectroscopies. Binding affinity of both DCF and CFT with BSA isobserved to be of the order of 10(4)M(-1), with the binding profiles fitting wellto the single set of binding site model. The disagreement between calorimetricand 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 uponligand binding as well as with increase in the temperature. Circular dichroismand the fluorescence results, however, do not show any major conformationalchanges upon binding of these drugs to BSA, and hence the discrepancy could bedue to temperature induced conformational changes in the protein. The results of ionic strength dependence and binding in the presence of anionic, cationic andnon-ionic surfactants indicate, involvement of more that a single type ofinteraction in the binding process. The ITC results for the binding of thesedrugs to BSA in presence of each other indicate that the binding sites for thetwo drugs are different, and therefore binding of one is not influenced by theother. The DSC results provide quantitative information on the effect of thesedrugs on the stability of serum albumin. The combined calorimetric andspectroscopic 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]