差分移动光谱学声学弹射质谱仪系统用于选异构化介导酶药物标
Samad Bazargan1, Patricia Dranchak2, Chang Liu1
1SCIEX, Concord, Ontario L4K 4V8, Canada.
Analytical chemistry
|December 19, 2024
概括
我们开发了DAEMS,这是一种结合离子流动性和质谱学的新型高通量选方法. 该系统有效地分离和量化代谢异构体,对于在传染病中识别新药标至关重要.
科学领域:
- 分析化学 分析化学
- 生物化学 生物化学
- 代谢学 代谢学 代谢学
背景情况:
- 代谢学涉及许多结构异构体,需要先进的分离技术.
- 目前的方法难以以高通量分离异构代谢产物.
- 异构酶酶在新陈代谢中至关重要,并代表潜在的药物点.
研究的目的:
- 引入和验证高通量查的DAEMS (差分移动光谱与声喷射质谱相结合).
- 证明DAEMS在复杂的生物样本中分离和量化结构异构体的能力.
- 通过分析异构酶活性来展示DAEMS作为识别药物标的工具.
主要方法:
- 微分移动谱学 (DMS) 与声弹射质谱学 (AEMS) 的整合.
- 开发超高吞吐量样本引入技术.
- 应用DAEMS用于同时量化基质和异构酶反应产物.
主要成果:
- 对糖酸盐和酸盐/异酸盐异构体实现了高分辨率 (1588年和1948年),超过了之前的代谢学研究.
- 成功证明了DAEMS用于分离iPGM,chorismate mutase和trio-phosphate isomerase的基板和产物.
- 由于与AEMS兼容的高速分离,没有内部标准的验证量化.
结论:
- 戴姆斯为需要异构体和异构体分离的高通量质谱学提供了独特的解决方案.
- 该系统可以有效地选异构酶活动,用于药物发现,特别是针对病原体特定的标.
- 在代谢分析和药物开发方面,DAEMS代表了一项重大进展.
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