Shi Jie-Hua, Chen Jun, Wang Jing, Zhu Ying-Yao
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, China; State Key Laboratory Breeding Base of Green Chemistry Synthesis Technology, Zhejiang University of Technology, Hangzhou 310032, China.
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, China.
Spectrochim Acta A Mol Biomol Spectrosc. 2015 Feb 5;136 Pt B:443-50. doi: 10.1016/j.saa.2014.09.056. Epub 2014 Sep 28.
The binding interaction of sorafenib with calf thymus DNA (ct-DNA) was studied using UV-vis absorption spectroscopy, fluorescence emission spectroscopy, circular dichroism (CD), viscosity measurement and molecular docking methods. The experimental results revealed that there was obvious binding interaction between sorafenib and ct-DNA. The binding constant (Kb) of sorafenib with ct-DNA was 5.6×10(3) M(-1) at 298 K. The enthalpy and entropy changes (ΔH(0) and ΔS(0)) in the binding process of sorafenib with ct-DNA were -27.66 KJ mol(-1) and -21.02 J mol(-1) K(-1), respectively, indicating that the main binding interaction forces were van der Waals force and hydrogen bonding. The docking results suggested that sorafenib preferred to bind on the minor groove of A-T rich DNA and the binding site of sorafenib was 4 base pairs long. The conformation change of sorafenib in the sorafenib-DNA complex was obviously observed and the change was close relation with the structure of DNA, implying that the flexibility of sorafenib molecule played an important role in the formation of the stable sorafenib-ct-DNA complex.
采用紫外可见吸收光谱、荧光发射光谱、圆二色光谱（CD）、粘度测量和分子对接方法研究了索拉非尼与小牛胸腺DNA（ct-DNA）的结合相互作用。实验结果表明，索拉非尼与ct-DNA之间存在明显的结合相互作用。在298 K时，索拉非尼与ct-DNA的结合常数（Kb）为5.6×10³ M⁻¹。索拉非尼与ct-DNA结合过程中的焓变和熵变（ΔH⁰和ΔS⁰）分别为-27.66 KJ mol⁻¹和-21.02 J mol⁻¹ K⁻¹，表明主要的结合相互作用力为范德华力和氢键。对接结果表明，索拉非尼倾向于结合在富含A-T的DNA小沟上，索拉非尼的结合位点长度为4个碱基对。明显观察到索拉非尼-DNA复合物中索拉非尼的构象变化，且该变化与DNA结构密切相关，这意味着索拉非尼分子的柔韧性在稳定的索拉非尼-ct-DNA复合物形成中起重要作用。
