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酸胺酶及其辅因子在生物治疗中的作用
Sisi Zhang1, Christopher Sevinsky1, Jared Watson1
1Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, New York 10591-6706, United States.
Molecular pharmaceutics
|December 9, 2025
概括
活性酸胺酶降解聚酸盐 (PSs),导致蛋白质药物的不稳定性. 有效的净化方法,如柱子再生和UF/DF过,可以防止这种降解.
科学领域:
- 生物化学 生物化学
- 制药科学 制药科学
- 蛋白质治疗药物 蛋白质治疗药物
背景情况:
- 聚酸盐 (PSs) 是生物制药配方中的关键辅助剂.
- 脂酶和酶活性可以降解PSs,导致蛋白质药物不稳定性和颗粒形成.
- 酸胺酶以前没有被认为是一种降解PS的酶.
研究的目的:
- 为了研究酸胺酶降解聚酸盐的潜力.
- 识别激活酸胺酶并影响其PS降解活性的因素.
- 确定在蛋白质药物净化过程中防止PS降解的方法.
主要方法:
- 对老化水相互作用色谱 (HIC) 列上的酸amidase活性进行分析.
- 评估素D对酸胺酶活性的影响.
- 超过/透过 (UF/DF) 对于索巴辛D去除的评估.
主要成果:
- 酸胺酶可以在老化的HIC柱上被激活,使得聚酸盐降解.
- 素D增强了激活酸amidase的脂酶活性,加速了PS的降解.
- 有效的HIC柱再生阻止了酸amidase的激活;UF/DF去除了saosin D.
结论:
- 激活的酸胺酶,特别是素D,在净化过程中对聚酸盐的稳定性构成风险.
- 标准的净化方案,包括有效的柱子再生和UF/DF过,可以减轻PS降解的风险.
- 这些发现表明,在根据当前指导方针净化产品中,被激活的酸胺酶降解聚酸盐不太可能.
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