Investigation on the site-selective binding of bovine serum albumin by erlotinib hydrochloride

Abstract

The purpose of this study was to investigate the site-selective binding of erlotinib hydrochloride (ET), a targeted anticancer drug, to bovine serum albumin (BSA) through 1H NMR, spectroscopic, thermodynamic, and molecular modeling methods. The fluorescence quenching of BSA by ET was a result of the formation of BSA–ET complex with high binding affinity. The site marker competition study combined with isothermal titration calorimetry experiment revealed that ET binds to site II of BSA mainly through hydrogen bond and van der Waals force. Molecular docking was further applied to define the specific binding site of ET to BSA. The conformation of BSA was changed in the presence of ET, revealed by synchronous fluorescence, circular dichroism, and three-dimensional fluorescence spectroscopy results. Further, NMR analysis of the complex revealed that the binding capacity contributed by the aromatic protons in the binding site of BSA might be greater than the aliphatic protons.

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Keywords:

• erlotinib hydrochloride
• bovine serum albumin
• spectroscopic methods
• thermodynamic parameters
• molecular docking

Acknowledgments

The authors would like to thank the financial support from National Basic Research Program of China (No. 2010CB933501), State Key Lab of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry.