通过同位素标记的降解二甲基化和质谱碎片化的循环软点的快速和最终识别
Yu Feng1, Athanasia Qirjollari1, Maria V Fawaz2
1Nonclinical Drug Safety, MRL, Merck & Co., Inc., 770 Sumneytown Pike, West Point, Pennsylvania 19486, United States.
Analytical chemistry
|May 1, 2024
概括
在循环中识别软点对于口服药物开发至关重要. 这项研究引入了一种新型的同位素标记二甲基化方法,用于快速和明确地识别这些地点,简化药物发现.
科学领域:
- 生物化学 生物化学
- 药用化学 医学化学
- 分析化学 分析化学
背景情况:
- 循环是一种日益增长的治疗类.
- 口服需要具有高蛋白质溶解稳定性的.
- 识别胺键水解部位 (软点) 是优化循环候选药物的关键.
研究的目的:
- 开发一种快速而确定的方法来识别循环软点.
- 为了克服由氨基酸键水解产生的等离子序列的挑战.
- 在药物发现过程中帮助优化循环的结构.
主要方法:
- 使用同位素标记的还原性二甲基化.
- 使用的质谱碎片化 (MS/MS).
- 分析了独特的离子,用于N端氨基酸识别.
主要成果:
- 开发了一种创新策略,用于快速和明确的软点识别.
- 证明二甲基化离子提供增强的MS信号.
- 展示了软点识别工作流程的简化.
结论:
- 以同位素标记的二甲基化是一种用于循环药物发现的强大工具.
- 这种方法使软点的明确表征成为可能.
- 促进循环的高效优化,用于治疗开发.
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