Thermodynamic study of indoxylsulfate interaction with human serum albumin and competitive binding with p-cresylsulfate

Indoxylsulfate (IS) and p-cresylsulfate (PCS) are natural compounds endowed with toxicity. These molecules are harmful to the environment and removed by the procedure of dialysis. Knowledge of their interaction with biologic compounds such as proteins and particularly human serum albumin (HSA) is limited. This study was therefore designed to determine the thermodynamic parameters of the interaction of IS with HSA and in competition with PCS. Results showed that IS binding is moderate (K _a = 1,750 ± 39 M^?1). The interaction is mainly electrostatic (?H° = ?36.2 ± 1.7 kJ mol^?1) and yields a modification of conformation upon binding (?_conf S° < 0). The thermodynamic parameters obtained at different temperatures show an enthalpy–entropy compensation process. Competition with PCS reveals that affinity for IS decreased by 36 %, with profound modification of the binding forces involved and a release of PCS from the binding site.