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通过超分子主客体相互作用对G-四链体结构和酶促反应进行可逆操纵。

Reversible manipulation of the G-quadruplex structures and enzymatic reactions through supramolecular host-guest interactions.

作者信息

Tian Tian, Song Yanyan, Wei Lai, Wang Jiaqi, Fu Boshi, He Zhiyong, Yang Xi-Ran, Wu Fan, Xu Guohua, Liu Si-Min, Li Conggang, Wang Shaoru, Zhou Xiang

机构信息

College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei Province, China.

College of Chemical Engineering and Technology, Wuhan University of Science and Technology, Wuhan 430081, Hubei Province, China.

出版信息

Nucleic Acids Res. 2017 Mar 17;45(5):2283-2293. doi: 10.1093/nar/gkx025.

DOI:10.1093/nar/gkx025
PMID:28115627
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5389557/
Abstract

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.

摘要

超分子化学研究分子间作用力,因此具有很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,尚未有关于G4超分子操纵的报道。本研究首次揭示了一种用于可逆控制人类端粒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。通过各种方法,我们表明葫芦[7]脲通过超分子相互作用优先锁定并包封拉佐带正电荷的哌啶。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景的途径,并在化学生物学的未来研究中展现出潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5389557/630997a9980b/gkx025fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5389557/7bd69dddecbd/gkx025fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5389557/c423e4ed0955/gkx025fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5389557/18402ea39505/gkx025fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5389557/b10a3d27e253/gkx025fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5389557/2052bbfa75a8/gkx025fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5389557/630997a9980b/gkx025fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5389557/7bd69dddecbd/gkx025fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5389557/c423e4ed0955/gkx025fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5389557/18402ea39505/gkx025fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5389557/b10a3d27e253/gkx025fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5389557/2052bbfa75a8/gkx025fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b2e/5389557/630997a9980b/gkx025fig6.jpg

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