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通过小角度中子散射测量NISTmAb的-交换动力学

Róisín B Donnelly^1,2, Sai Venkatesh Pingali³, Luke Heroux³

¹Department of Biomedical Engineering, College of Engineering, University of Delaware, Newark, Delaware 19711, United States.

Molecular pharmaceutics

|November 14, 2023

概括

小角度中子散射 (SANS) 为-交换 (HDX) 分析提供了一种新的,非侵入性的方法. 这种技术量化了蛋白质动态和结构稳定性,这对于生物制药开发至关重要.

科学领域:

生物物理化学生物物理化学
蛋白质科学蛋白质科学
分析化学分析化学

背景情况:

蛋白质动力学和结构稳定性对于生物制药研究至关重要.
-交换 (HDX) 是研究这些特性的一个关键方法.
传统的HDX方法通常依赖于水平的质谱法.

研究的目的:

探索和验证小角度中子散射 (SANS) 作为一个补充的,非侵入性的HDX技术.
使用HDX-SANS. 评估蛋白质的结构波动和稳定性.
研究配方条件,特别是霍夫迈斯特盐对蛋白质稳定性的影响.

主要方法:

使用-交换与小角度中子散射 (HDX-SANS) 相结合.
在长时间内,HDX-SANS监测了模型治疗抗体 (NISTmAb) 中的交换过程.
差分扫描热量计 (DSC) 用于在各种盐配方下探测热稳定性.

主要成果:

HDX-SANS成功地直接在抗体溶液中量化了HDX动力学.
在交换期间检测到三级和四级结构的微妙变化.
破坏稳定的盐 (例如,甲,硫酸盐) 增加了结构动态,即使在变质温度以下.

结论:

HDX-SANS是一种敏感且非侵入性的技术,用于评估蛋白质结构波动.
这种方法为抗体构造动力学和不同配方的稳定性提供了新的见解.
HDX-SANS显示出作为评估生物制药配方蛋白质稳定性的工具的巨大潜力.

关键词:

这就是为什么HDX HDX HDX 没有一个NISTmAbAb.没有SANS,就没有SANS.这是一种单克隆抗体.蛋白质动力学蛋白质动力学稳定的稳定性稳定的稳定性

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