疏水表面活性剂-DNA复合物 (Surf-DNA) 在无水条件下使DNA编码-图书馆兼容的脱碳氧化化能够实现
Pratik R Chheda1, Nicholas Simmons1, Zhicai Shi2
1Discovery Chemistry, Janssen Research & Development, LLC, San Diego, California 92121, United States.
Organic letters
|May 14, 2024
概括
用DNA编码的图书馆 (DEL) 能够发现药物,但受到水相容化学的限制. 这项研究引入了一种使用DNA - 阴离子表面活性剂复合用于有机溶剂中的反应的新工作流,扩大了DEL的化学多样性.
科学领域:
- 药用化学 医学化学
- 有机化学 有机化学
- 生物技术是生物技术.
背景情况:
- 用DNA编码的库 (DEL) 对于识别小分子候选药物至关重要.
- 目前的DEL化学局限于水态条件,限制了化学多样性.
- 扩大对有机溶剂的DEL反应兼容性对于更广泛的命中发现至关重要.
研究的目的:
- 开发一种新的工作流程,使无水有机溶剂中的DNA编码库反应成为可能.
- 扩大可用于DNA编码图书馆选的化学空间.
- 促进新型小分子疗法的发现.
主要方法:
- 利用DNA - 阴离子表面活性剂复合,使得在有机溶剂中溶解和对DNA的反应.
- 在无水条件下开发了一种DEL兼容的光氧解碳化C(sp2) -C(sp3) 合反应.
- 优化了工作流程,以适用于大规模DEL生产的96井格式.
主要成果:
- 在无水有机溶剂中成功证明了DNA的反应.
- 建立了一个与DEL技术相容的新型光氧解碳化合反应.
- 该工作流允许有效选和优化有机介质中的反应.
结论:
- 呈现的工作流显著扩大了DNA编码库的化学空间.
- 这种方法可以使用各种有机反应进行DEL选.
- 这种方法准备加速在药物发现中发现新的小分子命中药物的发现.
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