Thermodynamic properties of GAPDH inhibitors by isothermal titration calorimetry

Abstract

The isothermal titration calorimetry (ITC) is a powerful thermodynamic technique that is employed in various stages of discovery and development of drugs. In this project, this technique will be used to obtain the association constant (Ka) and Gibbs free energy (deltaG) corresponding reaction stoichiometry (n), enthalpy (deltaH) and entropy (deltaS) for Trypanosoma cruzi and human GAPDH inhibitors. The thermodynamic signature of enzyme-ligand interactions and their analysis is essential for the complete understanding of the thermodynamic process of interaction. The determination of enzyme stability is accomplished by nano-differential scanning calorimetry (n-DSC), which is obtained through the temperature of protein denaturation and changing the heat capacity of the system. Through the description of the thermodynamic profile of known inhibitors of GAPDH, a profile of the inhibitors will be drawn with the goal of identifying the essential characteristics necessary for the description of the thermodynamic reasons for bimolecular interaction. (AU)