School of Chemistry and Environmental Science, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang, Henan 453007, PR China.
J Pharm Biomed Anal. 2011 Jul 15;55(5):1223-6. doi: 10.1016/j.jpba.2011.03.006. Epub 2011 Mar 10.
In this paper, binding interaction of 5-(ethoxycarbonyl)-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one (EMMD) with human serum albumin (HSA) under physiological conditions was investigated by using spectroscopy, isothermal titration calorimetry (ITC) and molecular modeling techniques. The results of spectroscopic studies suggested that EMMD have a strong ability to quench the intrinsic fluorescence of HSA through static quenching procedure. ITC investigations indicated that drug-protein complex was stabilized by hydrophobic forces and hydrogen bonds, which was consistent with the results of molecular modeling studies. Competitive experiments indicated the displacement of warfarin by EMMD, which revealed that the binding site of EMMD to HSA was located at subdomain IIA.
本文采用光谱法、等温滴定量热法（ITC）和分子模拟技术研究了生理条件下 5-(乙氧羰基)-6-甲基-4-(4-甲氧基苯基)-3,4-二氢嘧啶-2(1H)-酮（EMMD）与人血清白蛋白（HSA）的结合相互作用。光谱研究结果表明，EMMD 通过静态猝灭过程具有很强的猝灭 HSA 本征荧光的能力。ITC 研究表明，药物-蛋白质复合物是通过疏水作用力和氢键稳定的，这与分子模拟研究的结果一致。竞争实验表明，EMMD 置换了华法林，这表明 EMMD 与 HSA 的结合位点位于亚域 IIA。
