冰状态下的蛋白质聚合是由下降应力诱导的
Tetsuo Torisu1, Ayuko Maeda1, Shuhei Ito1
1Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
概括
意外掉落的冷蛋白质药物可以导致聚集在-30°C由于局部的热量产生. 使用Poloxamer-188或快速冷等配方策略可以在运输过程中防止这种蛋白质聚合.
科学领域:
- 生物制药开发 生物制药开发
- 蛋白质的稳定性 蛋白质的稳定性
- 物理化学 物理化学
背景情况:
- 生物制药中的蛋白质聚合物可能会导致免疫性,降低药物的疗效和安全性.
- 在运输和处理过程中,减压对冷蛋白质药物的物理稳定性的影响仍未得到充分研究.
研究的目的:
- 为了研究压力下降对冷Fc融合蛋白的物理稳定性的影响.
- 确定冷蛋白质中压力下降诱导的聚合背后的机制.
- 评估防止压力下降引起的聚合的策略.
主要方法:
- 在不同温度 (-30°C和-60°C) 上,将冷的Fc融合蛋白瓶子置于下降应力下.
- 量化聚合物度的增加,特别是微米大小的聚合物.
- 分析蛋白质吸附到瓶子表面的情况.
- 调查局部热量产生和解压力的作用.
- 评估Poloxamer-188和快速冷在防止聚合中的有效性.
主要成果:
- 在-30°C时观察到微米大小的聚合物显著增加,但在-60°C时没有.
- 降落应激诱导蛋白质聚合主要是通过局部热量产生引起结解应激,而不是瓶表面脱离.
- 波洛克萨默-188有效地减轻了在-30°C下降应力引起的聚合.
- 快速冷也抑制了压力下降引起的聚合.
结论:
- 压力下降会损害蛋白质的稳定性,即使在冷状态下也是如此.
- 降落事件期间的局部热量产生是冷解诱导蛋白质聚合的关键因素.
- 配方和冷过程的优化,包括使用Poloxamer-188等辅助剂和快速冷,对于在运输过程中保持蛋白质稳定至关重要.
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