Bovine serum albumin binding study to erlotinib using surface plasmon resonance and molecular docking methods

Publication year: 2018
Authors: Taghipour P. 1, Zakariazadeh M. 2, Sharifi M. 3, Ezzati Nazhad Dolatabadi J. 4, Barzegar A. 5
Affiliations:

1 - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Research Institute for Fundamental Sciences (RIFS), University of Tabriz, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
2 - Research Institute for Fundamental Sciences (RIFS), University of Tabriz, Tabriz, Iran
3 - Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4 - Research Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
5 - Research Institute for Fundamental Sciences (RIFS), University of Tabriz, Tabriz, Iran

Published in: Journal of Photochemistry and Photobiology B, 2018, Vol. 183, p. 11-15
doi: 10.1016/j.jphotobiol.2018.04.008

Bovine serum albumin (BSA) is the most abundant protein in the blood circulation and it is commonly used for drug delivery in blood. Therefore, we aim to study BSA interaction with erlotinib as an anticancer drug using surface plasmon resonance (SPR) and molecular modeling methods under physiological conditions (pH = 7.4). BSA immobilized on carboxymethyl dextran hydrogel Au chip (CMD) after activation with N-hydroxysuccinimide and N-ethyl-N-(3-diethylaminopropyl) carbodiimide and then the erlotinib binding to BSA at different concentrations was evaluated. Increasing of erlotinib concentration led to dose-response sensorgrams of BSA. The amount of equilibrium constant (KD) at 25 °C (4.25 × 10-9) showed the high affinity of erlotinib to BSA. Thermodynamic parameters were attained at four different temperatures. The positive value of enthalpy and entropy showed that hydrophobic forces play major role in the interaction of erlotinib with BSA. Besides, the positive value of Gibbs free energy demonstrated that the interaction of erlotinib with BSA was nonspontaneous and enthalpy driven and the complexion of drug were dependent on endothermic process. According to the molecular docking study, the most favorable binding sites of erlotinib on the BSA were subdomain IIIA and IB. Moreover, molecular docking study results showed that hydrogen binding has a role in intermolecular force that stabilize erlotinib-BSA complex.


MP-SPR keywords: binding in different temperatures, CMD sensor slides, molecular docking studies, protein amino coupling, small molecule – protein interaction, thermodynamic study