Investigation on the site-selective binding of bovine serum albumin by erlotinib hydrochloride.
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. An animated interactive 3D complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:26.
a The State Key Lab of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences , Fuzhou , Fujian , 350002 , P.R. China.
Yan
Y
Liu
Mingmao
M
Chen
Zhipu
Z
Luo
Jingjing
J
Lin
Ling
L
Song
D001665:Binding Sites; D002942:Circular Dichroism; D000069347:Erlotinib Hydrochloride; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011799:Quinazolines / Q000737:chemistry* / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
D011799:Quinazolines; D012710:Serum Albumin, Bovine; D000069347:Erlotinib Hydrochloride