化学空间的快速探索 通过高吞吐量吸附电喷射电离质谱
Kai-Hung Huang1, Nicolás M Morato1, Yunfei Feng1
1Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United States.
Journal of the American Chemical Society
|November 19, 2024
概括
吸附电喷离 (DESI) 能够快速合成和分析药物类型. 这种高吞吐量方法探索了药物发现的广化学空间,
科学领域:
- 分析化学
- 有机合成
- 药物发现
背景情况:
- 在微滴的溶液/空气界面加速的化学反应是探索化学空间的关键.
- 吸附电喷离 (DESI) 提供了一个快速合成和分析的平台.
研究的目的:
- 利用DESI进行高吞吐量合成和药物模拟化学空间的探索.
- 研究DESI介导反应的效率和范围,以产生多种药物衍生物.
主要方法:
- 使用DESI产生微滴以加速低纳米级反应.
- 在药物分子上进行多种化学转换 (电友/核友,氧化还原,C-H功能化,合).
- 使用质谱 (MS) 直接检测和表征产品,包括协同MS.
主要成果:
- 合成的药物类似物每秒速达1次反应混合物 (>3000次反应/小时).
- 在环境,毫秒条件下成功转化多种药物功能.
- 确定了3000多种独特的衍生品,其中1000多种还具有协同MS的特征.
结论:
- 高速的DESI-MS反应屏幕可以快速访问广泛的药物类型,用于生物活性测试.
- 这种方法加快了有机合成预测,并使未来的在线生物测试和扩大微滴合成成为可能.
- 通过快速选化合物库,为传统的药物发现工作流提供潜在的优势.
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