Sha Yijie, Chen Xu, Niu Bing, Chen Qin
Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, P. R. China.
Experimental Center for Life Science, Shanghai University, Shanghai, P. R. China.
Chem Biodivers. 2017 Oct;14(10). doi: 10.1002/cbdv.201700133. Epub 2017 Sep 27.
Quercetin, a ubiquitous flavanoid, has numerous pharmacological effects, such as antioxidant and antitumor. Previous studies showed nucleic acids were the potential biological targets for antitumor medicine. For exploring the mechanism of DNA-target medicine, the interaction between quercetin and calf thymus DNA was studied based on the method of spectrometry and simulation in our study. Firstly, the interaction between quercetin and calf thymus DNA was confirmed by fluorescence spectrometry. Furthermore, circular dichroism, fluorescence polarization, competitive displacement assay, and salt concentration dependence assay were applied to search the interaction mode of quercetin-calf thymus DNA, which proved the existence of groove binding and electrostatic interaction. Meanwhile, quenching constant K , binding constant K and the number of binding sites n was calculated, inferring that the fluorescence quenching occurred by static quenching process, and the main acting force was hydrogen bond. Finally, molecular docking was used to simulate and analyze the interaction between quercetin and calf thymus DNA.
槲皮素是一种普遍存在的类黄酮，具有多种药理作用，如抗氧化和抗肿瘤作用。先前的研究表明核酸是抗肿瘤药物潜在的生物学靶点。为了探究DNA靶向药物的作用机制，本研究采用光谱法和模拟方法研究了槲皮素与小牛胸腺DNA之间的相互作用。首先，通过荧光光谱法证实了槲皮素与小牛胸腺DNA之间的相互作用。此外，应用圆二色光谱、荧光偏振、竞争置换实验和盐浓度依赖性实验来探寻槲皮素与小牛胸腺DNA的相互作用模式，结果证明存在沟槽结合和静电相互作用。同时，计算了猝灭常数K、结合常数K和结合位点数n，推断荧光猝灭是由静态猝灭过程引起的，主要作用力是氢键。最后，利用分子对接技术对槲皮素与小牛胸腺DNA之间的相互作用进行了模拟和分析。
