Title
Probing the binding reaction of cytarabine to human serum albumin using multispectroscopic techniques with the aid of molecular docking
Author
Liang Xu, Yan-Xi Hu, Jin Li, Yu-Feng Liu, Li Zhang, Hai-Xin Ai, Hong-Sheng Liu
Year
2017
Journal
Journal of Photochemistry and Photobiology B: Biology
Abstract
Cytarabine is a kind of chemotherapy medication. In the present study, the molecular interaction between cytarabine and human serum albumin (HSA) was investigated via fluorescence, UV–vis absorption, circular dichroism (CD) spectroscopy and molecular docking method under simulative physiological conditions. It was found that cytarabine could effectively quench the intrinsic fluorescence of HSA through a static quenching process. The apparent binding constants between drug and HSA at 288, 293 and 298 K were estimated to be in the order of 103 L·mol− 1. The thermodynamic parameters ΔH°, ΔG°and ΔS° were calculated, in which the negative ΔG°suggested that the binding of cytarabine to HSA was spontaneous, moreover the negative ΔS°and negative ΔH°revealed that van der Waals force and hydrogen bonds were the major forces to stabilize the protein-cytarabine (1:1) complex. The competitive binding experiments showed that the primary binding site of cytarabine was located in the site I (subdomain IIA) of HSA. In addition, the binding distance was calculated to be 3.4 nm according to the Förster no-radiation energy transfer theory. The analysis of CD and three-dimensional (3D) fluorescence spectra demonstrated that the binding of drug to HSA induced some conformational changes in HSA. The molecular docking study also led to the same conclusion obtained from the spectral results.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Ligand binding, Biochemistry