在肠道环境中Fab抗体聚合的整个过程及其聚合调节:从静态和度扰动聚合的洞察力
Minquan Xia1, Lixian Ding2, Dong Uk Ahn3
1College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; College of Food Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China.
International journal of biological macromolecules
|February 8, 2025
概括
在模拟的肠液中,Fab抗体的聚合取决于度,由结构变化驱动. 诸如PEG 10000和Tween 20之类的辅助剂抑制聚合,有助于口服抗体治疗的发展.
科学领域:
- 生物化学 生物化学
- 制药科学 制药科学
- 蛋白质化学 蛋白质化学
背景情况:
- 口服抗体治疗由于胃肠道环境中的蛋白质聚合而面临挑战.
- 了解Fab抗体聚合的机制对于开发稳定的口服配方至关重要.
研究的目的:
- 为了阐明模拟肠液中Fab抗体的聚合和聚合抑制机制.
- 确定提高Fab抗体稳定性的策略,用于口服输送.
主要方法:
- 使用了静态和度扰动聚合试验.
- 随着时间的推移 (0-240分钟) 监测Fab抗体聚合.
- 用分子对接和分子动力学模拟来研究抑制剂相互作用.
主要成果:
- 法布聚合是度依赖的,受β-sheet堆叠和β-strand扭曲的影响.
- 聚合涉及构造性重新排列,扩大疏水核和扩展β片结构.
- 辅助剂 (Arg,PEG 10000,Poloxamer 188,Tween 20) 降低了潜在能量,并增强了固体阻碍,抑制了聚合.
结论:
- 在模拟的肠液中描述了Fab抗体聚合机制.
- 特定的辅助剂显示出稳定Fab抗体抗聚合的潜力.
- 这些发现支持开发基于Fab的口服抗体疗法.
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