Li Wei, Zhang Ming, Zhang Jin-li, Li Hui-qing, Zhang Xiao-chen, Sun Qian, Qiu Chun-mei
Department of Chemical Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
FEBS Lett. 2006 Sep 4;580(20):4905-10. doi: 10.1016/j.febslet.2006.08.007. Epub 2006 Aug 14.
The potential interaction of daidzin, an ingredient of soy isoflavones, with human telomeric antiparallel G-quadruplex dAG(3)(T(2)AG(3))(3) was studied using ESI-MS, PAGE, CD and molecular simulation. Experimental studies indicated that daidzin molecules interacted with dAG(3)(T(2)AG(3))(3) and formed DNA-daidzin complex with the stoichiometric ratio of 1:1 and 1:2. The transition temperature of the G-quadruplex increased at higher ratio of daidzin to DNA. Under molecular crowding conditions the interactions between daidzin and the G-quadruplex become much stronger. Combining computational simulation and experimental results, it is demonstrated that the dAG(3)(T(2)AG(3))(3)/daidzin complex with a stoichiometric ratio of 1:1 is stabilized through the pi-pi conjugacy interactions and hydrogen bondings between daidzin and the bases of G-quadruplex. This work provides guidance not only on exploring the molecular anti-cancer mechanism of dietary isoflavones, but also searching small natural products as promising anticancer candidates that can inhibit telomerase activity.
采用电喷雾电离质谱（ESI-MS）、聚丙烯酰胺凝胶电泳（PAGE）、圆二色光谱（CD）和分子模拟等方法，研究了大豆异黄酮成分大豆苷与人类端粒反平行G-四链体dAG(3)(T(2)AG(3))(3)之间的潜在相互作用。实验研究表明，大豆苷分子与dAG(3)(T(2)AG(3))(3)相互作用，形成化学计量比为1:1和1:2的DNA-大豆苷复合物。大豆苷与DNA比例越高，G-四链体的转变温度越高。在分子拥挤条件下，大豆苷与G-四链体之间的相互作用变得更强。结合计算模拟和实验结果表明，化学计量比为1:1的dAG(3)(T(2)AG(3))(3)/大豆苷复合物通过大豆苷与G-四链体碱基之间的π-π共轭相互作用和氢键得以稳定。这项工作不仅为探索膳食异黄酮的分子抗癌机制提供了指导，也为寻找有潜力抑制端粒酶活性的天然抗癌候选小分子提供了指导。
