油对治疗抗体的结构,稳定性和聚合性的影响
Vaibhav Upadhyay1, Sudipta Panja1, Yogita Krishnamachari2
1Center for Pharmaceutical Biotechnology, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 E Montview Blvd, MS C238-V20, Aurora, CO 80045, United States.
Journal of pharmaceutical sciences
|May 25, 2025
概括
预装注射器中的油与dupilumab的结合很弱,但不会改变其结构. 然而,它在热应力下加速蛋白质聚合,影响治疗蛋白质的稳定性.
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:
- 预装注射器中的油涂层有助于蛋白质治疗的设备功能.
- 蛋白质聚合是治疗疗效和安全的关键问题.
- 了解蛋白质-油相互作用对于生物制药发展至关重要.
研究的目的:
- 为了研究油和模型蛋白质dupilumab之间的结合相互作用.
- 评估油对杜比卢马布的结构和形状稳定性的影响.
- 阐明油影响蛋白质聚合的机制.
主要方法:
- 异热定位热量计 (ITC) 用于结合分析.
- 循环二重化 (CD) 和内在光用于结构稳定性.
- 核磁共振 (NMR) 光谱检测形状变化.
- 前面光,流量成像和动态光散射 (DLS) 用于总体表征.
主要成果:
- 在油和dupilumab之间观察到微弱的疏水性相互作用 (毫米相亲).
- 没有检测到dupilumab的结构或形状稳定性的显著变化.
- 油在热应力下加速蛋白质聚合,可能通过降低体稳定性或诱导部分展开.
结论:
- 油不会破坏dupilumab本源结构的稳定性.
- 在特定的压力条件下,油可以促进蛋白质聚合.
- 需要进一步的研究,以减轻蛋白质疗法中油诱导的聚合.
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