对于DNA编码图书馆合成的squaramide形成
Antoine Douchez1, Julien Poupart1, Gaoqiang Yang1
1Drug Discovery Unit, Institute of Research in Immunology and Cancer, Université de Montréal, Montréal, Quebec H3C 3J7, Canada.
Bioconjugate chemistry
|June 14, 2024
概括
用DNA编码的图书馆 (DEL) 允许发现小分子. 一种新的,温和的squaramide反应是DNA安全的,并且与DELs兼容,扩大了药物发现的可访问化学支架.
科学领域:
- 药用化学 医学化学
- 化学生物学 化学生物学
- 有机合成 有机合成
背景情况:
- DNA编码库 (DEL) 是发现生物活性的小分子的强大工具.
- 在DEL的关键挑战包括开发水相反应,最大限度地减少DNA损伤,并纳入各种化学构件.
- 在DEL中获得药物化学的新型支架通常受到DNA支持的化学约束的限制.
研究的目的:
- 开发一种新的,与DNA兼容的化学转换,用于DNA编码图书馆合成.
- 建立一个强大的方胺形成反应,适合在DNA化学.
- 扩大使用DEL技术用于药物发现的可访问化学支架的范围.
主要方法:
- 设计和优化了一种两步方胺形成反应.
- 评估了反应与水条件的兼容性和DNA完整性.
- 评估了反应对各种功能组的耐受性及其产量.
主要成果:
- 成功开发了一种温和高产的两步方胺形成反应.
- 该反应对广泛的功能群体表现出极好的耐受性.
- 该方法被证明对DNA是安全的,导致最小的改变.
- 该反应适合集成到DNA编码库工作流程中.
结论:
- 开发的正方体形成反应是DNA编码库的理想方法.
- 这种进步扩大了通过DELs可访问的化学支架的范围.
- 这种反应有助于发现具有潜在生物应用的新型小分子.
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