使用光超极化 (CIDNP) NMR 的超快断片查
Felix Torres1,2, Matthias Bütikofer1, Gabriela R Stadler1
1ETH, Swiss Federal Institute of Technology, Laboratory of Physical Chemistry, Vladimir-Prelog-Weg 2, CH-8093 Zürich, Switzerland.
Journal of the American Chemical Society
|May 25, 2023
概括
光化学诱导的动态核极化 (光CIDNP) 增强了基于片段的药物设计的NMR. 该方法使用低度检测弱结合剂,并显著加快选速度.
科学领域:
- 生物化学
- 化学生物学
- 药物发现
背景情况:
- 核磁共振 (NMR) 是基于片段的药物设计的一个关键技术.
- 高通量NMR查受到低灵敏度的限制,需要高样本度和长时间的采集时间.
研究的目的:
- 通过超极化改进NMR的灵敏度和效率,用于基于片段的药物设计.
- 证明光化学诱导的动态核极化 (光CIDNP) 适用于检测水溶液中的弱结合物.
主要方法:
- 使用光化学诱导的动态核极化 (光CIDNP) 来增强NMR灵敏度.
- 开发了一种用于高通量选的自动流通平台.
- 选了一个包含212个组合的CIDNP片段库.
主要成果:
- 在低微分子连接物 (5 μM) 和目标 (2 μM) 度下检测到具有毫米相亲的弱结合物.
- 通过利用光 CIDNP 增加 1-2 个数量级的信号噪声.
- 通过极化火识别结合,在2-5秒单扫描实验中比标准技术提高了100倍.
结论:
- 照片CIDNP提供了一种灵敏和高效的方法,用于在水溶液中基于片段的药物发现.
- 开发的自动化平台可以快速查每天1500个样本.
- 这种方法为使用光CIDNP进行基于片段的综合选铺平了道路.
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