Quantitative Analysis of Nucleic Acid Stability with Ligands Under High Pressure to Design Novel Drugs Targeting G-Quadruplexes

Q4 Chemistry
Shuntaro Takahashi, Naoki Sugimoto
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引用次数: 3

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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current Protocols in Nucleic Acid Chemistry
Current Protocols in Nucleic Acid Chemistry Chemistry-Organic Chemistry
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期刊介绍: Published in association with International Society for Nucleosides, Nucleotides & Nucleic Acids (IS3NA) , Current Protocols in Nucleic Acid Chemistry is equally valuable for biotech, pharmaceutical, and academic labs. It is the resource for designing and running successful research projects in the rapidly growing and changing field of nucleic acid, nucleotide, and nucleoside research.
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