Binding of esketamine to human serum albumin for clinical implications

Abstract

The interaction of the newly approved pharmacon esketamine with HSA (human serum albumin) has been investigated by various spectrographic methods. The fluorescence quenching results of HSA by esketamine revealed that the 1:1 ground state complex has formed. The results of binding parameters lead to the conclusion that the reaction was exothermic. In the presence of esketamine, HSA was found to undergo partial unfolding, and thermodynamic parameters (ΔG° = − 2.08 × 10⁴ J·mol⁻¹, ΔS° = 35.7 J·mol⁻¹·K⁻¹, and ΔH° = − 1.20 × 10⁴ J·mol⁻¹ at 298 K) revealed that electrostatic forces dominated the stabilization of the complex. The qualitative and quantitative analyses of conformational changes of HSA were conducted using circular dichroism, three-dimensional, and synchronous fluorescence spectroscopy, revealing the loosening of skeleton structure and adaptive modifications of secondary structures. Fe³⁺ and Mg²⁺ may help prolong the storage time and improve the drug efficacy.