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通过小分子DNA结合剂实现可编程的动态DNA化学

Junpeng Xu^1,2, Guan Alex Wang¹, Lu Gao¹

¹Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu, Sichuan, 610064, P. R. China.

Nature communications

|July 17, 2023

概括

与DNA结合的小分子可以编程动态DNA反应. 这种结合剂诱导的核酸移位 (BIND) 方法加速了DNA结合化合物的发现和表征.

科学领域:

生物化学生物化学
分子生物学分子生物学
化学生物学化学生物学

背景情况:

通过介质或小沟结合与DNA相互作用的小分子可以改变DNA的稳定性和功能.
这些相互作用是开发治疗剂和生物传感器的基础.

研究的目的:

引入和验证一种新的方法,即结合剂诱导的核酸移位 (BIND),用于编程动态DNA反应.
为了证明BIND在特征DNA结合剂和发现新的生物活性小分子方面的实用性.

主要方法:

利用小分子DNA结合剂定量调节的DNA链位移反应.
开发一个单一的,公正的分子平台,以全面描述DNA结合剂,评估亲和力和序列选择性.
设计一个双联BIND系统,用于复合库的高通量选.

主要成果:

使用小分子DNA结合剂对DNA链位移反应进行了量化控制.
在没有专门的设备的情况下,成功地描述了现有的和确定了新的DNA结合剂.
在700种化合物的库中发现了8种新的DNA结合剂,使用了并联结合测试.

结论:

BIND提供了一种创新的方法,可以加速发现和描述针对DNA的生物活性小分子.
BIND平台提供了一种无偏见的,无需设备的方法来评估关键的DNA绑定器参数.
BIND促进了新型DNA结合化合物的高通量选,证明了其在药物发现和化学生物学中的潜力.

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