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{"title":"Quantitative Analysis of Nucleic Acid Stability with Ligands Under High Pressure to Design Novel Drugs Targeting G-Quadruplexes","authors":"Shuntaro Takahashi, Naoki Sugimoto","doi":"10.1002/cpnc.39","DOIUrl":null,"url":null,"abstract":"<p>Nucleic acids (DNA and RNA) can form various non-canonical structures. Because some serious diseases are caused by the conformational change of G-quadruplex DNA structures, the development of ligands that bind and stabilize G-quadruplex DNA is of interest to the field of nucleic acid chemistry. Volumetric changes (Δ<i>V</i>) in the biomolecular reaction include the structural change of biomolecules and hydration behaviors, which provide information about the tertiary interaction between G-quadruplex DNA and ligands. Thus, it is valuable to investigate Δ<i>V</i> values to understand the mechanism of interaction between non-canonical structures and their ligands. This unit describes methods that can be used to quantitatively analyze the interaction between G-quadruplex DNA and ligands by using high-pressure UV melting. The combination of thermodynamic parameters (Δ<i>G</i>, Δ<i>H</i>, Δ<i>S</i>, and Δ<i>V</i>) is a powerful tool to elucidate the mechanism of ligand binding to G-quadruplex without real structural analysis by NMR and X-ray spectroscopy, and gives useful information to design novel drugs. © 2017 by John Wiley & Sons, Inc.</p>","PeriodicalId":10966,"journal":{"name":"Current Protocols in Nucleic Acid Chemistry","volume":"70 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2018-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cpnc.39","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Protocols in Nucleic Acid Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cpnc.39","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Chemistry","Score":null,"Total":0}
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Abstract
Nucleic acids (DNA and RNA) can form various non-canonical structures. Because some serious diseases are caused by the conformational change of G-quadruplex DNA structures, the development of ligands that bind and stabilize G-quadruplex DNA is of interest to the field of nucleic acid chemistry. Volumetric changes (ΔV ) in the biomolecular reaction include the structural change of biomolecules and hydration behaviors, which provide information about the tertiary interaction between G-quadruplex DNA and ligands. Thus, it is valuable to investigate ΔV values to understand the mechanism of interaction between non-canonical structures and their ligands. This unit describes methods that can be used to quantitatively analyze the interaction between G-quadruplex DNA and ligands by using high-pressure UV melting. The combination of thermodynamic parameters (ΔG , ΔH , ΔS , and ΔV ) is a powerful tool to elucidate the mechanism of ligand binding to G-quadruplex without real structural analysis by NMR and X-ray spectroscopy, and gives useful information to design novel drugs. © 2017 by John Wiley & Sons, Inc.
高压下配体核酸稳定性定量分析设计靶向g -四联体药物
核酸(DNA和RNA)可以形成各种非规范结构。由于一些严重的疾病是由g -四重体DNA结构的构象变化引起的,因此开发结合和稳定g -四重体DNA的配体是核酸化学领域的研究热点。生物分子反应中的体积变化(ΔV)包括生物分子的结构变化和水合行为,它提供了g -四重体DNA与配体之间的三级相互作用的信息。因此,研究ΔV值对于理解非规范结构与其配体之间的相互作用机制是有价值的。本单元介绍了通过高压紫外熔融定量分析g -四重体DNA与配体之间相互作用的方法。热力学参数(ΔG, ΔH, ΔS, ΔV)的组合是一个强大的工具来阐明配体与g -四联体结合的机制,而不需要通过核磁共振和x射线光谱进行真正的结构分析,并为设计新药提供有用的信息。©2017 by John Wiley &儿子,Inc。
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