Reversible manipulation of the G-quadruplex structures and enzymatic reactions through supramolecular host-guest interactions.
Reversible manipulation of the G-quadruplex structures and enzymatic reactions through supramolecular host-guest interactions.
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通过超分子主客体相互作用可逆操纵G-四链体结构和酶反应
DOI：
10.1093/nar/gkx025
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发表时间：
2017-03-17
影响因子：
14.9
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Tian T;Song Y;Wei L;Wang J;Fu B;He Z;Yang XR;Wu F;Xu G;Liu SM;Li C;Wang S;Zhou X
超分子化学解决了分子间力的问题，因此具有极大的灵活性和精确性。生物系统常常是超分子研究的灵感来源。 G-四链体（G4）属于核酸中最重要的二级结构之一。直到最近，G4 的超分子操纵尚未见报道。本研究首次公开了可逆控制人类端粒G4的超分子开关。此外，这种超分子开关已成功用于操纵酶促反应。使用各种方法，我们证明葫芦[7]脲通过超分子相互作用优选地锁定和封装Razo带正电荷的哌啶。它们可以在柔性状态和刚性 G4 之间切换 DNA 抑制剂的构象，因此负责凝血酶活性的可逆控制。因此，我们的研究结果开辟了一条有前途的途径，并在未来的化学生物学研究中展示了潜在的应用。
Supramolecular chemistry addresses intermolecular forces and consequently promises great flexibility and precision. Biological systems are often the inspirations for supramolecular research. The G-quadruplex (G4) belongs to one of the most important secondary structures in nucleic acids. Until recently, the supramolecular manipulation of the G4 has not been reported. The present study is the first to disclose a supramolecular switch for the reversible control of human telomere G4s. Moreover, this supramolecular switch has been successfully used to manipulate an enzymatic reaction. Using various methods, we show that cucurbit[7]uril preferably locks and encapsulates the positively charged piperidines of Razo through supramolecular interactions. They can switch the conformations of the DNA inhibitor between a flexible state and the rigid G4 and are therefore responsible for the reversible control of the thrombin activity. Thus, our findings open a promising route and exhibit potential applications in future studies of chemical biology.