物理化学学报 >> 2010, Vol. 26 >> Issue (04): 1082-1086.doi: 10.3866/PKU.WHXB20100416

生物物理化学 上一篇    下一篇

电喷雾质谱法研究天然产物小分子识别人类端粒G-四链体及复合物的热稳定性

何湘伟, 龙海涛, 袁谷, 徐筱杰, 周亚伟   

  1. 北京大学化学与分子工程学院化学生物学系, 北京分子科学国家实验室, 生物有机与分子工程教育部重点实验室, 北京 100871; 北京大学化学与分子工程学院, 北京 100871; 北京大学世佳研究中心, 北京 100084
  • 收稿日期:2009-11-03 修回日期:2010-01-12 发布日期:2010-04-02
  • 通讯作者: 袁谷 E-mail:guyuan@pku.edu.cn

Investigation of Interaction of Small Natural Product Molecules and Human Telomeric G-Quadruplex and Thermal Stabilities of the Complexes by Electrospray Ionization Mass Spectrometry

HE Xiang-Wei, LONG Hai-Tao, YUAN Gu, Xu Xiao-Jie, ZHOU Ya-Wei   

  1. Beijing National Laboratory for Molecular Science, Key Laboratory of Bioorganic and Molecular Engineering of Education Ministry, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. China; College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. China; Baschoior Research Center, Peking University, Beijing 100084, P. R. China
  • Received:2009-11-03 Revised:2010-01-12 Published:2010-04-02
  • Contact: YUAN Gu E-mail:guyuan@pku.edu.cn

摘要:

利用电喷雾质谱(ESI-MS)研究了12种天然产物小分子与人类端粒G-四链体结构的非共价相互作用和识别功能, 比较了不同小分子与人类端粒G-四链体的结合强弱, 发现了一种新的识别小分子——防己诺林碱对人类端粒G-四链体有很好的结合. 通过质谱升温实验比较了小分子结合对G-四链体热稳定性的影响, 防己诺林碱的结合使G-四链体的离子的解离温度(T1/2)上升到200 ℃. 利用分子模拟对G-四链体DNA与小分子结合的模式以及稳定性进行了探讨, 给出了防己诺林碱可能的结合位点和结合模式, Autodock计算出来的结合能约为-31.5 kJ·mol-1. 同原来的平面型分子不同, 防己诺林碱是一类新型结构的分子, 为设计合成新型G-四链体识别分子提供了新的结构模型.

关键词: 分子模拟, 端粒, G-四链体DNA, 天然产物小分子, 电喷雾质谱

Abstract:

Electrospray ionization mass spectrometry (ESI-MS) was used to investigate the non-covalent interaction of human telomeric G-quadruplex (G4) DNA with 12 natural product molecules. We found that Fangchinoline, a new ligand of the human telomeric G-quadruplex, had the highest binding affinity among these molecules. The stabilities of the G-quadruplex and the complexes of the G-quadruplex with small molecules were investigated using a mass spectrometry heating experiment. By Fangchinoline binding, the dissociation temperature (T1/2) value of the complex of G-quadruplex with the ligand increased to 200 ℃. We studied the binding mode and stability of the G-quadruplex with the small molecules using Autodock. Possible binding sites were found and the binding energy was about -31.5 kJ·mol -1. Unlike the typical binding molecules with a planar structure, Fangchinoline is a new kind of G-quadruplex ligand and it gives us a different insight for the design of new G-quadruplex ligands.

Key words: Molecular modeling, Telomere, G-quadruplex DNA, Natural product molecule, Electrospray ionization mass spectrometry

MSC2000: 

  • O641