高通量药物衍生和生物试验通过脱电喷射电离子化质谱法
Jyotirmoy Ghosh1, Nicolás M Morato1, Yunfei Feng1
1Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN, 47907, USA.
ChemPlusChem
|March 17, 2025
概括
高通量 (HT) 方法通过快速合成和改性药物的生物活性测试来加速药物发现. 这项研究展示了自动晚期功能化和生物测试,使用脱电喷雾电离化质谱法 (DESI MS).
科学领域:
- 药用化学 医学化学
- 分析化学 分析化学
- 药物发现 药物发现 药物发现
背景情况:
- 药物发现依赖于高效的合成和生物活性测试.
- 高通量 (HT) 方法对于加速这一过程至关重要.
- 晚期功能化 (LSF) 允许药物候选者的快速多样化.
研究的目的:
- 为了证明HT脱电喷雾电离质谱法 (DESI MS) 对药物的LSF的适用性.
- 快速生成和描述一个修改的阿片类药物库.
- 在一个单一的平台上将LSF与HT生物测试集成在一起,以加速药物发现.
主要方法:
- 使用自动化的HT-DESI MS平台进行药物修饰.
- 用于LSF的阿扎-迈克尔添加和硫 (VI) 化物交换反应.
- 在每秒 >1 个反应的反应产品特征进行了MS 分析.
- 使用DESI-MS.对原始反应混合物进行了无标签的HT生物测试.
主要成果:
- 通过使用HT-DESIMS成功证明了nor-opioid支架的LSF.
- 产生并描述了功能化阿片类类似物多样化的图书馆.
- 实现了快速的合成和分析,在滴滴飞行过程中发生反应.
- 集成的LSF和生物测试,允许直接评估结构-活动关系.
结论:
- 自动化的HT-DESI MS平台通过LSF加速创建各种药物库.
- 在同一平台上将加速LSF与直接生物测试相结合,显著加快了早期药物发现.
- 这种综合方法为新药开发提供了快速的结构-活性关系评估.
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