药学学报, 2021, 56(10): 2779-2786
引用本文:
汪泓, 尹红锐, 陈益乐, 方欣欣, 徐明明, 田橙, 徐进, 陈钢, 邵泓. 治疗类糖蛋白的糖基化分析[J]. 药学学报, 2021, 56(10): 2779-2786.
WANG Hong, YIN Hong-rui, CHEN Yi-le, FANG Xin-xin, XU Ming-ming, TIAN Cheng, XU Jin, CHEN Gang, SHAO Hong. Glycosylation analysis of therapeutic proteins[J]. Acta Pharmaceutica Sinica, 2021, 56(10): 2779-2786.

治疗类糖蛋白的糖基化分析
汪泓1, 尹红锐1, 陈益乐2, 方欣欣1, 徐明明1, 田橙2, 徐进3, 陈钢1, 邵泓1*
1. 上海市食品药品检验研究院, 国家药品监督管理局治疗类单抗质量控制重点实验室, 上海 201203;
2. 上海药明生物技术有限公司分析科学部, 上海 200131;
3. 上海张江生物技术有限公司, 抗体药物与靶向治疗国家重点实验室, 国家药品监督管理局治疗类单抗质量控制重点实验室, 上海 201203
摘要:
糖基化作为至关重要的一种蛋白质翻译后修饰,在治疗类糖蛋白的安全性、有效性、质量可控性中起到关键性作用。然而,糖基化为非模板依赖性的酶促修饰,具有天然的异质性,使得糖基化的分析成为治疗类糖蛋白表征及质控的一个挑战。为了推动治疗类糖蛋白的技术法规建立及质控水平提高,本文从治疗类糖蛋白糖基化分析的核心理念、分析策略、良好分析的实施以及技术趋势4个方面进行深入探讨,力图为我国工业界治疗类糖蛋白糖基化分析提供参考,推动我国糖蛋白类生物医药产业的发展。
关键词:    治疗类糖蛋白      糖基化分析      核心理念     
Glycosylation analysis of therapeutic proteins
WANG Hong1, YIN Hong-rui1, CHEN Yi-le2, FANG Xin-xin1, XU Ming-ming1, TIAN Cheng2, XU Jin3, CHEN Gang1, SHAO Hong1*
1. Shanghai Institute for Food and Drug Control, NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai 201203, China;
2. Analytical Sciences, WuXi Biologics (Shanghai) Co., Ltd., Shanghai 200131, China;
3. State Key Laboratory of Antibody Medicine and Targeted Therapy, NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai Zhangjiang Biotechnology Co., Ltd., Shanghai 201203, China
Abstract:
As one of the most critical post-translational modifications, glycosylation of therapeutic proteins has a profound impact on their safety, efficacy and consistent. However, glycosylation is not a template-driven process, therefore variability in the glycosylation pattern of a protein can arise. This makes challenges of glycan analysis and control. Here, we review the overall control strategy, basic requirements for standardized protocols and the novel technologies of glycosylation analysis to accelerate the development of therapeutic glycoproteins.
Key words:    therapeutic glycoprotein    glycosylation analysis    overall control strategy   
收稿日期: 2021-04-17
DOI: 10.16438/j.0513-4870.2021-0579
基金项目: 国家自然科学基金青年科学基金资助项目(81803422);上海市科委技术标准项目(20DZ2200700).
通讯作者: 邵泓,Tel:86-21-50798176,E-mail:shaohong@smda.sh.cn
Email: shaohong@smda.sh.cn
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