作为聚酸盐氧化过程的关键元素,化聚氧乙烯链的微粒溶剂可访问性:密度功能理论,分子动力学模拟和液体染色学/质谱研究
Johanna Weber1, Leonardo Pedri2, Luis P Peters2
1Institute of Pharmacy, Faculty of Biosciences, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, Halle 06120, Germany.
Molecular pharmaceutics
|February 3, 2025
概括
聚酸盐 (PS) 的氧化裂变损害了蛋白质的稳定性. 这项研究确定了聚酸盐20的关键降解部位,揭示了氧化如何影响两性和蛋白质保护.
科学领域:
- 制药科学 制药科学
- 物理化学 物理化学
- 生物化学 生物化学
背景情况:
- 聚酸盐 (PS) 是蛋白质稳定的关键辅助剂.
- 它们的两性阻止了蛋白质的聚合.
- 对于生物制药配方来说,PS的氧化降解是一个重大问题.
研究的目的:
- 确定驱动聚酸盐氧化裂变的因素.
- 确定聚酸盐分子内的首选降解点.
- 了解降解对蛋白质颗粒形成的影响.
主要方法:
- 概念密度函数理论 (DFT) 的计算.
- 分子动力学 (MD) 模拟.分子动力学 (MD) 模拟.
- 在氧化应激 (Fe2+,光) 和不同的储存条件下对聚酸盐20的试验性降解研究.
主要成果:
- MD模拟显示,未化聚氧乙烯 (POE) 链最容易被水接入,容易氧化.
- 氧化的POE链的氧化裂变,特别是在环附近,不利于蛋白质的稳定.
- 降解产品表明聚酸盐的基本两性丧失.
结论:
- 这项研究阐明了聚酸盐中关键的氧化降解途径.
- 了解这些途径对于预测和预防PS降解至关重要.
- 这些知识支持开发更稳定的生物制药配方.
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