摘要
糖化是一个重要的蛋白质修饰过程,可能影响治疗性蛋白药物(如单克隆抗体药物)的生物活性及分子稳定性。许多研究表明糖化血红蛋白水平升高与心血管疾病及动脉粥样硬化有着密切关系。人体的血浆蛋白,如白蛋白、球蛋白、纤维蛋白和胶原蛋白也可能被糖化,进而形成AGEs,蛋白药物的生产、储存以及药物在体内循环过程中都可能发生糖化反应。综述了治疗性抗体药物糖化的原因、分析方法,以及糖化对抗体药物生物学功能的影响,以期为临床抗体药物的开发、优化及贮存条件研究提供参考。
Glycation is an important protein modification that could potentially affect bioactivity and molecular stability of the rapeutic proteins such as monoclonal antibodies. Many studies suggested that elevated levels of glycated hemoglobin were closely related with cardiovascular disease and atherosclerosis. Human plasma proteins,such as albumin,globulin,fibrinogen and collagen may be glycosylated,and then forms AGEs. In this paper,we reviewed the root cause and the current analytical methods of glycation of the rapeutic antibodies. We also summarized the effect of glycation on biological function,which was expected to provided reference for research on development,optimizion and storage condition of the rapeutic antibodies.
作者
张斌
刘晓志
周敬华
魏敬双
高健
王志明
ZHANG Bin;LIU Xiaozhi;ZHOU Jmghua;WEI Jlngshuang;GAO Jian;WANG Zhiming(State Key Laboratory of Antibody Research & Development, New Drug Research and Development Company Ltd., North China Pharmaceutical Corporation, Shijiazhuang 050015, China;Hebei Province Family Planning Research Institute Male Laboratory, Shijiazhuang 050000, China)
出处
《生物技术进展》
2018年第1期28-33,共6页
Current Biotechnology
基金
国家重大新药创制项目(2014ZX09201041-004)资助