热和pH压力决定了单克隆抗体聚合的不同机制
Hoi Kong Meng1, Kuin Tian Pang2, Corrine Wan1
1Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
International journal of biological macromolecules
|October 20, 2024
概括
单克隆抗体 (mAbs) 中的蛋白质聚合受热和pH压力的影响. 酸性pH促进展开驱动的聚合,而热量通过集群-集群机制导致更大的聚合物,影响生物稳定性.
科学领域:
- 生物制药开发 生物制药开发
- 蛋白质化学 蛋白质化学
- 化学工程是化学工程的重要组成部分.
背景情况:
- 蛋白质聚合是单克隆抗体 (mAb) 发育中的一个关键挑战.
- 在生产过程中的压力条件可以显著加剧mAb聚合.
- 了解聚合机制对于确保生物稳定性和有效性至关重要.
研究的目的:
- 研究热和pH压力对mAb聚合机制的影响.
- 在不同的压力条件下阐明不同的聚合路径.
- 为评估在加速压力下 mAb 聚合提供一个定量框架.
主要方法:
- mAb聚合的实验性表征.
- 聚合路径的动态建模.
- 在不同的pH值和温度下分析聚合物的尺寸和性能.
主要成果:
- 热和pH压力之间的复杂相互作用显著影响mAb稳定性.
- 酸性pH主要通过mAb展开驱动聚合.
- 更高的温度通过单体独立的集群-集群聚合促进了更大的聚合物形成.
结论:
- 外在的压力条件是mAb聚合倾向的关键决定因素.
- 在不同的压力条件下,不同的机制是mAb聚合的基础.
- 这些发现为通过管理压力条件开发更稳定的生物制剂提供了一个框架.
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