使用电荷状态操纵,碰撞激活和离子移动性质谱法量差异化抗体
Theresa A Gozzo1, Matthew F Bush1
1Department of Chemistry, University of Washington, Box 351700, Seattle, Washington 98195-1700, United States.
Analytical chemistry
|December 26, 2023
概括
将阴离子转离子反应 (CAPTR) 与离子流动性质谱学 (IM-MS) 结合起来,可以改善抗体治疗的特征和差异化. 这种先进的技术增强了结构分析,以便更好地开发药物.
科学领域:
- 生物化学 生物化学
- 分析化学 分析化学
- 制药科学 制药科学
背景情况:
- 抗体疗法越来越重要,但也带来了特征化的挑战.
- 离子移动性质谱法 (IM-MS) 有助于更高层次的结构分析.
- 能源依赖的IM-MS (例如,碰撞引起的展开) 检测到微妙的结构变化.
研究的目的:
- 研究离子转离子反应 (CAPTR) 和依赖能量的IM-MS对抗体气相结构的联合作用.
- 增强人类IgG1κ和IgG4κ髓瘤蛋白质的特征和差异化.
- 评估CAPTR在改善电荷状态赋值和解决干扰物种方面的实用性.
主要方法:
- 利用阴离子转阳子转移反应 (CAPTR) 来降低电荷.
- 采用了依赖能源的离子移动性质谱法 (IM-MS).
- 在不同的溶液条件下分析了人类IgG1κ和IgG4κ髓瘤蛋白.
- 应用相似度评分用于对碰撞横截面分布的定量比较.
主要成果:
- CAPTR提高了对充电状态赋值的信心,并解决了干扰蛋白种.
- 确定了电荷减小抗体产物的碰撞横截面分布.
- 与能量依赖的IM-MS结合CAPTR,与单独的IM-MS相比,显著增强了抗体分化.
结论:
- 阴离子转离子反应 (CAPTR) 对抗体表征有很大的好处.
- 将CAPTR与能源依赖的IM-MS集成,为区分抗体结构提供了一个强大的方法.
- 这种综合方法推进了用于抗体治疗开发的分析工具包.
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