一种双分子同时宏循环化策略,以合成循环二核类同类物与核酸间关联的关联
Di Xie1, Jiwei Tang1, Tingting Zhang1
1Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, P. R. China.
研究人员开发了一种新的9步方法,用于合成具有guanidinium链接的循环二核酸 (CDN) 类似物. 这些新型CDN类似物显示出作为STING激动剂和细菌生物膜抑制剂的潜力,其中一种化合物抑制了大肠杆菌生物膜的形成.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 分子生物学分子生物学
背景情况:
- 核酸间瓜尼迪尼链接模仿聚,增强了寡核酸的特性.
- 目前用于循环二核酸 (CDN) 模拟合成的方法是漫长而复杂的.
研究的目的:
- 为了开发一个更有效的合成CDN类似物与瓜尼尼链接.
- 评估这些CDN类似物作为STING激动剂和抗菌剂的潜力.
主要方法:
- 采用了一种新的9步双分子同时宏循环化 (BSM) 协议.
- 一个共享密钥中间体被用来合成CDN类似物与各种核基.
- 测试了CDN类似物,以检测哺乳动物细胞中的STING激动性和细菌中的生物膜抑制.
主要成果:
- 该BSM协议显著减少了合成步骤从26到9.
- 化合物13c证明了对大肠杆菌的强烈生物膜抑制 (54%在78μM).
结论:
- 开发的BSM协议为CDN模拟合成提供了一种简化方法.
- 有关关 guanidinium 链接的 CDN 类型对治疗应用,包括抗微生物策略具有前景.
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