调整i-motif折叠和稳定性与非循环酸盐结合 (ZNA) 酸丁残留物
Marlies Derden1, Sten Reynders1, Jérôme Rihon1
1KU Leuven, Rega Institute for Medical Research, Medicinal Chemistry Herestraat 49-Box 1041 3000 Leuven Belgium elisabetta.groaz@kuleuven.be eveline.lescrinier@kuleuven.be.
RSC advances
|October 9, 2025
概括
研究人员修改了i-Motifs (iM),一个四链DNA结构,使用新型核酸来增强稳定性. 用5 - 化素 (5F-C) 进行的修改改变了跨pH范围的IM稳定性,显示了生物医学应用的潜力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 核酸化学的核酸化学
背景情况:
- i-Motifs (iMs) 是非正规的DNA结构,由半质子化细胞因子:细胞因子对稳定.
- 在非酸性pH值下的细胞因子脱会导致IM展开,限制它们的应用.
- 需要进行修改,以扩大iM的稳定性,以应用于潜在的生物医学用途.
研究的目的:
- 研究与细胞因子 (C) 或5-细胞因子 (5F-C) 结合的非循环酸盐结合核酸 (ZNA) 对IM稳定性的影响.
- 探索ZNA的修改,以在更广泛的环境条件下实现IM形成.
- 分析ZNA替代对脊椎动物端粒IMS的结构动态的影响.
主要方法:
- 紫外线化和核磁共振 (NMR) 谱学以评估iM的稳定性和结构.
- 分子动力学 (MD) 模拟以可视化本地和修改的IMs中的循环动力学.
- 合成和纳入ZNA-C和ZNA-5F-C的 (R) 和 (S) 异构体到一个22-mer脊椎动物端粒iM序列中.
主要成果:
- 加入ZNA-C降低了IM的稳定性.
- 含有ZNA的5F-C在各种pH水平上改变了iM的稳定性.
- 模拟MD显示了修改iMS的循环动态变化,与稳定性降低相关.
- 对于 (R) 和 (S) -ZNA修改,都观察到稳定的基配对.
结论:
- ZNA的修改,特别是5F-C,可以在不同的pH条件下调节iM的稳定性.
- 修改后的IMS中变化的循环动力学有助于降低它们的稳定性.
- 这些发现提供了设计IMS用于特定的生物医学应用的见解,通过调整其环境稳定性.
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