Biophysical study on the interaction of etomidate and the carrier protein in vitro

Abstract

Etomidate is a unique drug used for induction of general anesthesia and sedation, and is usually used through intravenous injection clinically. Before targeting to the receptor, etomidate binds proteins in blood when it comes into veins. Thus to study the interaction of etomidate and serum albumin would be of great toxicological and pharmacological importance. In this study, the interaction between etomidate and human serum albumin (HSA) was studied using fluorescence spectroscopy, UV–vis absorption spectroscopy, Fourier transform infrared spectroscopy (FT-IR), circular dichroism (CD) spectroscopy, site maker displacement and molecular modeling methods. Investigations of the binding constant (K = 3.55 × 105 M−1, 295 K), the number of binding sites (n = 1.16), thermodynamic parameters (ΔG = 3.13 × 104 J·mol−1, ΔS = 364 J·mol−1·K−1 and ΔH = −6.85 × 105 J·mol−1) for the reaction and changes to the binding sites and conformation in HSA in response to etomidate were presented. Results show that etomidate can bind HSA tightly through electrostatic forces, and the protein skeleton conformation and secondary structure changes thereby. This is the first spectroscopic report for etomidate–HSA interactions which illustrates the complex nature of this subject.