Exploring the interaction between the antiallergic drug, tranilast and human serum albumin: Insights from calorimetric, spectroscopic and modeling studies
Document Type
Article
Publication Date
1-1-2015
Abstract
The interaction of tranilast (TRN), an antiallergic drug with the main drug transporter in human circulation, human serum albumin (HSA) was studied using isothermal titration calorimetry (ITC), fluorescence spectroscopy and in silico docking methods. ITC data revealed the binding constant and stoichiometry of binding as (3.21 ± 0.23) × 106 M-1 and 0.80 ± 0.08, respectively, at 25 °C. The values of the standard enthalpy change (ΔH°) and the standard entropy change (ΔS°) for the interaction were found as -25.2 ± 5.1 kJ mol-1 and 46.9 ± 5.4 J mol-1 K-1, respectively. Both thermodynamic data and modeling results suggested the involvement of hydrogen bonding, hydrophobic and van der Waals forces in the complex formation. Three-dimensional fluorescence data of TRN-HSA complex demonstrated significant changes in the microenvironment around the protein fluorophores upon drug binding. Competitive drug displacement results as well as modeling data concluded the preferred binding site of TRN as Sudlow's site I on HSA.
Keywords
Tranilast, Human serum albumin, Isothermal titration calorimetry, Ligand binding, Molecular docking
Divisions
InstituteofBiologicalSciences
Funders
Ministry of Education, Government of Malaysia and the University of Malaya: High Impact Research MoE Grant UM.C/625/1/HIR/MoE/SC/02
Publication Title
International Journal of Pharmaceutics
Volume
491
Issue
1-2
Publisher
Elsevier