Optical, structural and thermodynamic studies of the association of an anti-leucamic drug imatinib mesylate with transport protein.

The interaction of an anti-leukemic drug, imatinib mesylate (IMT) with human serum albumin (HSA) was investigated by fluorescence, synchronous fluorescence, three-dimensional fluorescence, circular dichroism and UV-vis absorption techniques under physiological condition. The process of binding of IMT on HSA was observed to be through a spontaneous molecular interaction procedure. IMT effectively quenched the intrinsic fluorescence of HSA via static quenching. The values of binding constant, number of molecules that interact simultaneously with the binding site and thermodynamic parameters were evaluated by carrying out the interactions at three different temperatures. Based on thermodynamic parameters and displacement studies with site probes, it was proposed that the drug bound at Sudlow's site I of subdomain IIA. The change in the conformation of HSA was evident from synchronous, three-dimensional fluorescence and circular dichroism studies. The distance between the donor (protein) and acceptor (drug) was calculated based on the Foster's theory of resonance energy stransfer and it was found to be 1.30 nm. The effect of different metal ions on the binding of the drug to protein was also investigated.