Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5398490 | Journal of Luminescence | 2016 | 34 Pages |
Abstract
The interaction of SB202190, a p38 mitogen-activated protein kinase inhibitor with the main drug transporter in human circulation, human serum albumin (HSA) was studied using fluorescence spectroscopy and in silico docking methods. The association constant, Ka of the binding reaction was determined to be 3.24±0.07Ã104 Mâ1 at 25 °C based on fluorescence quenching titration results. The values of enthalpy change and entropy change for the interaction were found as â8.54 kJ molâ1 and 58.01 J molâ1 Kâ1, respectively. Both thermodynamic data and docking results suggested the involvement of hydrophobic and van der Waals forces in the complex formation. Three-dimensional fluorescence data of SB202190-HSA complex demonstrated significant changes in the microenvironment around the protein fluorophores upon drug binding. Comparison of HSA thermograms obtained in the absence and the presence of SB202190 suggested improved protein thermal stability upon complexation with the drug. Competitive drug displacement results as well as modeling data concluded the preferred binding site of SB202190 on HSA as Sudlow׳s site I.
Keywords
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Physical Sciences and Engineering
Chemistry
Physical and Theoretical Chemistry
Authors
Ahmad N. Nasruddin, Shevin R. Feroz, Abdul K. Mukarram, Saharuddin B. Mohamad, Saad Tayyab,