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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2010, Vol. 30 Issue (04): 101-109    
综述     
蛋白药物的聚乙二醇定点修饰策略与最佳位点
王旭东1,李晓晖1,苏志国2,修志龙1**
1.大连理工大学环境与生命学院 大连 116024
2.中国科学院过程工程研究所生化工程国家重点实验室 北京 100190
Site-specific PEGylation Strategies and Suitable Modified Sites of Protein Drugs
WANG Xu-dong1,LI Xiao-hui1,SU Zhi-guo2,XIU Zhi-long1
1.School of Environmental and Biological Science and Technology, Dalian University of Technology, Dalian 116024, China.
2.State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
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摘要:

聚乙二醇修饰是一种改善蛋白质药物临床药效行之有效的方法。聚乙二醇修饰具有延长蛋白质药物在体内的半衰期、降低免疫原性和延缓蛋白酶降解、提高稳定性和溶解性等优点。而聚乙二醇的定点修饰由于能够获得均一性和高活性保留率的产物,并能提高产率,已经引起了广泛关注。综述了近年来聚乙二醇定点修饰蛋白质药物方面的研究进展,着重介绍了聚乙二醇定点修饰的策略及最佳修饰位点,并对聚乙二醇定点修饰技术的发展趋势进行了展望。

关键词: 聚乙二醇定点修饰固相修饰位置异构体分子模拟    
Abstract:

PEGylation, the covalent attachment of polyethylene glycol (PEG) to proteins, has been used as an effective strategy to overcome several shortcomings of proteins for therapeutic uses. The therapeutic efficacy of PEGylated protein drugs can be improved through prolonging their circulating half-life, reducing their immunogenicity and proteolysis, and increasing their stability and solubility. Furthermore, site-specific PEGylation is an attractive approach for the maximizing the bioavailability of drugs, because a homogeneously modified product with high activity retention and yield can be achieved. Recent advances in site-specific PEGylation were reviewed. The site-specific PEGylation strategies and suitable modified sites were particularly introduced. Finally, the future trends and prospects in site-specific PEGylation were discussed.

Key words: Site-specificPEGylation    Solid phase PEGylation    Positional isomer    Molecular simulation
收稿日期: 2009-12-30 出版日期: 2010-04-29
基金资助:

国家“863”计划资助项目(2007AA021604)863 计划

通讯作者: 修志龙     E-mail: zhlxiu@dlut.edu.cn
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引用本文:

王旭东 李晓晖 苏志国 修志龙. 蛋白药物的聚乙二醇定点修饰策略与最佳位点[J]. 中国生物工程杂志, 2010, 30(04): 101-109.

WANG Xu-Dong, LI Xiao-Hui, SU Zhi-Guo, XIU Zhi-Long. Site-specific PEGylation Strategies and Suitable Modified Sites of Protein Drugs. China Biotechnology, 2010, 30(04): 101-109.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/        https://manu60.magtech.com.cn/biotech/CN/Y2010/V30/I04/101

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