Unravelling the molecular interaction of diselenodipropionic acid (DSePA) with human serum albumin (HSA)

Abstract

Diselenodipropionic acid (DSePA), a selenocystine derivative, has emerged as a promising pharmacologically active organoselenium compound. In order to fully utilize its activity, there is a need to understand its transport mechanism as well as interaction with circulatory proteins like human serum albumin (HSA). Accordingly, interaction between DSePA and HSA has been investigated in this study by employing integrated spectroscopic and docking methods. Both absorption and fluorescence spectra of HSA showed significant changes on addition of DSePA. From these changes the binding constant (K_b) has been estimated to be (2.5 ± 0.1) × 10⁵ M⁻¹ and (3.2 ± 0.3) × 10⁵ M⁻¹, respectively by employing Benessi-Hildebrand and modified Stern-Volmer equations. The molecular interaction was also corroborated by isothermal titration calorimetry (ITC) with mono-model fitting, from which binding constant (K_b) value was also estimated. The HSA-DSePA complex was analyzed by small angle X-ray scattering and circular dichroism techniques. Molecular docking studies suggested that DSePA binds at domain IIA with specific molecular interactions at Trp214, Lys199, Arg222, Ala291, Leu238, Arg257 amino acid residues. These results provide evidence for the interaction between DSePA and HSA and similar tools can be extrapolated to understand interaction with many other proteins during its metabolic process.