Interaction between HSA and a thiosemicarbazide derivative: Analysis of the effect of a methyl group in the binding ability

Abstract

The interaction between the methyl thiosemicarbazide derivative ETS2 and Human Serum Albumin (HSA) - the main vehicle of biodistribution of small molecules in the human bloodstream - was evaluated by multiple spectroscopic techniques (circular dichroism, steady state, time-resolved, synchronous and 3D fluorescence) under physiological conditions, combined with theoretical calculations (molecular docking). The interaction HSA:ETS2 is spontaneous, moderate and is already present in the ground state (static association). Increasing the temperature leads to an increase in binding and the association is entropically driven. The secondary structure of the protein does not suffer significant perturbation upon ligand binding, however, there is a perturbation on the microenvironment around the Trp-214 residue. Sudlow’s site I is the main binding site and molecular docking results suggest hydrogen bonding and hydrophobic interactions as the main binding forces. Overall, the presence of the methyl group in the ligand structure does not change significantly the protein structure, however, the presence of this group changed the thermodynamic profile, which strongly suggests that the methyl group decreases the binding ability of the thiosemicarbazide towards serum albumin.