一个双特异单克隆抗体的两个域间二硫化物键变体的高阶结构特征
Ivan L Budyak1, Lihua Huang1, Rina K Dukor2
1Biopharmaceutical Research and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States.
Journal of pharmaceutical sciences
|May 16, 2024
概括
了解蛋白质高阶结构 (HOS) 对生物学至关重要. 这项研究使用了多种生物物理技术来分析抗体变体,揭示了二硫化物键混杂如何影响结构和稳定性.
科学领域:
- 生物化学 生化学
- 蛋白质科学 蛋白质科学
- 生物制药开发 生物制药开发
背景情况:
- 蛋白质高阶结构 (HOS) 对生物制剂的疗效至关重要.
- 在整个生物制药开发过程中,评估结构完整性至关重要.
研究的目的:
- 描述双特异单克隆抗体的两个折叠变体.
- 为了阐明二硫化键混杂对抗体结构和热稳定性的影响.
主要方法:
- 不同扫描热量计 (DSC)
- 循环二元化 (CD) 光谱学 循环二元化 (CD) 光谱学
- 福里埃转换红外光谱法 (FTIR)
- 拉曼和拉曼光学活动 (ROA) 光谱学.
主要成果:
- 鉴定了一种替代抗体配置,由于二硫化物键混杂,其强度降低.
- 证明了组合生物物理技术对HOS特征的实用性.
- 量化了结构变化对热稳定性的影响.
结论:
- 在scFv域中的二硫化键混杂显著影响双特异抗体结构和稳定性.
- 生物物理特征方法的选择对于检测HOS变化至关重要.
- 全面的HOS分析对于成功的生物制剂开发至关重要.
关键词:
圆形二重化 (CD) 是指一个圆形的二重化.不同扫描热量计 (DSC)里埃变换红外光谱法 (FTIR) 是一种方法.单克隆抗体 (monoclonal antibody) 是一种单克隆的抗体.拉曼光学活动 (ROA)拉曼光谱法 拉曼光谱法 拉曼光谱法mAb-scFvv 的意思是什么意思更多相关视频
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