开发出专门与双链 RNA(而非双链 DNA)结合的阳离子寡二氨基半乳糖

IF 3.1 2区 化学 Q2 CHEMISTRY, ANALYTICAL
Hidetaka Torigoe , Sumire Nakayama , Tomomi Shiraishi , Kazuki Sato , Rintaro Iwata Hara , Takeshi Wada
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引用次数: 0

摘要

双链 RNA 的稳定对于人工沉默基因表达的应用非常重要。过量使用与双链 RNA 结合亲和力低的阳离子分子可能会由于非特异性结合而导致细胞毒性。与双链 RNA 有特异性结合的高亲和力阳离子分子是稳定双链 RNA 所必需的。在这里,紫外熔融和等温滴定量热分析表明,我们之前设计的阳离子寡二氨基半乳糖 4 mer(ODAGal4)能以约 105 M-1 的结合常数特异性地稳定双链 RNA,而不与双链 DNA 结合。热力学参数(包括负焓和负熵变化)的温度依赖性表明,与双链 RNA 结合的小分子的负热容量变化幅度相当大,这表明疏水效应对结合过程有影响。我们的研究结果表明,ODAGal4 是双链 RNA 结合特异性的关键分子,可防止任何非特异性结合,具有治疗作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Development of cationic oligodiaminogalactoses specifically binding to duplex RNA, but not to duplex DNA

Development of cationic oligodiaminogalactoses specifically binding to duplex RNA, but not to duplex DNA

Duplex RNA stabilization is important for the application in the artificial silencing of gene expression. Excess usage of cationic molecules with low binding affinity to duplex RNA may cause cytotoxicity due to nonspecific binding. Cationic molecules specifically binding to duplex RNA with high binding affinity are necessary for duplex RNA stabilization. Here, UV melting and isothermal titration calorimetric analyses revealed that our previously designed cationic oligodiaminogalactose 4 mer (ODAGal4) specifically stabilized duplex RNA by binding to it with approximately 105 M−1 binding constant, without binding to duplex DNA. Temperature dependence of thermodynamic parameters, including negative enthalpy and entropy changes, revealed that the magnitude of negative heat capacity change was quite large for small molecules binding to duplex RNA, suggesting the influence of the hydrophobic effect on the binding process. Our results suggest the therapeutic application of ODAGal4 as a key molecule for duplex RNA-binding specificity to prevent any nonspecific binding.

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来源期刊
Thermochimica Acta
Thermochimica Acta 化学-分析化学
CiteScore
6.50
自引率
8.60%
发文量
210
审稿时长
40 days
期刊介绍: Thermochimica Acta publishes original research contributions covering all aspects of thermoanalytical and calorimetric methods and their application to experimental chemistry, physics, biology and engineering. The journal aims to span the whole range from fundamental research to practical application. The journal focuses on the research that advances physical and analytical science of thermal phenomena. Therefore, the manuscripts are expected to provide important insights into the thermal phenomena studied or to propose significant improvements of analytical or computational techniques employed in thermal studies. Manuscripts that report the results of routine thermal measurements are not suitable for publication in Thermochimica Acta. The journal particularly welcomes papers from newly emerging areas as well as from the traditional strength areas: - New and improved instrumentation and methods - Thermal properties and behavior of materials - Kinetics of thermally stimulated processes
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