Investigation on the site-selective binding of bovine serum albumin by erlotinib hydrochloride
Investigation on the site-selective binding of bovine serum albumin by erlotinib hydrochloride
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DOI：
10.1080/07391102.2012.726532
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发表时间：
2013-10-01
影响因子：
4.4
通讯作者：
Song, Ling
中科院分区：
文献类型：
--
作者：
Liu, Yan;Chen, Mingmao;Song, Ling
本研究旨在通过1H NMR、光谱、热力学和分子模拟方法研究靶向抗癌药物盐酸厄洛替尼（ET）与牛血清白蛋白（BSA）的位点选择性结合。ET对BSA的荧光猝灭是由于BSA与ET形成了高亲和力的复合物。结合等温滴定量热法的位点标记竞争研究表明，ET主要通过氢键和货车范德华力与BSA的位点II结合。进一步应用分子对接技术确定了ET与BSA的特异性结合位点。同步荧光光谱、圆二色谱和三维荧光光谱结果表明，ET的存在改变了BSA的构象。此外，NMR分析的复合物显示，在BSA的结合位点的芳香族质子贡献的结合能力可能大于脂肪族质子。一个动画交互式3D补充（I3DC）可在Proteopedia上获得，
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