Investigating the Antagonistic Action Between Aspirin and Tamoxifen with HSA: Identification of Binding Sites in Binary and Ternary Drug-Protein Systems by Spectroscopic and Molecular Modeling Approaches

Title: Investigating the Antagonistic Action Between Aspirin and Tamoxifen with HSA: Identification of Binding Sites in Binary and Ternary Drug-Protein Systems by Spectroscopic and Molecular Modeling Approaches

Volume: 18 Issue: 3

Author(s): Sanaz Pourgonabadi, Mohammad Reza Saberi and Jamshid Khan Chamani

Affiliation:

Keywords: HAS, aspirin, tamoxifen, spectroscopy, fluorescence quenching, circular dichroism, resonance light scattering, molecular dynamicsHAS, aspirin, tamoxifen, spectroscopy, fluorescence quenching, circular dichroism, resonance light scattering, molecular dynamics

Abstract: The combination of several drugs is often necessary, especially during long-term therapy. A competitive binding of the drugs can cause a decrease of the amount of drugs actually bound to the protein and increase the biologically active fraction of the drug. The aim of this study has been to analyze the interactions of tamoxifen (TMX) and aspirin (ASA) with human serum albumin (HSA) and to evaluate the mechanism of a simultaneous binding of TMX and ASA to the protein. Fluorescence analysis was used to estimate the effect of the drugs on the protein fluorescence and to define the binding and quenching properties of drug-HSA complexes. The binding sites for TMX and ASA were identified in ternary structures of HSA by means of spectrofluroscence. The analysis of the fluorescence quenching of HSA in binary and ternary systems pointed at TMX and ASA having an effect on the HSA-ASA and HSA-TMX complexes. Furthermore, the results of synchronous fluorescence, resonance light scattering and circular dichroism of the binary and ternary systems showed that the binding of TMX and ASA to HSA could induce conformational changes in HSA. Moreover, the simultaneous presence of TMX and ASA during binding to HSA should be taken into account in multi-drug therapy, as it induces the necessity of a monitoring therapy owing to the possible increase of uncontrolled toxic effects. Competitive site marker experiments demonstrated that the binding site of ASA and TMX to HSA differed in the binary system as opposed to in its ternary counterpart. Finally, molecular modeling of the possible binding sites of TMX and ASA in binary and ternary systems to HSA confirmed the experimental results.

Cite this article as:

Pourgonabadi Sanaz, Reza Saberi Mohammad and Khan Chamani Jamshid, Investigating the Antagonistic Action Between Aspirin and Tamoxifen with HSA: Identification of Binding Sites in Binary and Ternary Drug-Protein Systems by Spectroscopic and Molecular Modeling Approaches, Protein & Peptide Letters 2011; 18 (3) . https://dx.doi.org/10.2174/092986611794578350

DOI https://dx.doi.org/10.2174/092986611794578350	Print ISSN 0929-8665
Publisher Name Bentham Science Publisher	Online ISSN 1875-5305