典型文献
Global characterization of modifications to the charge isomers of IgG antibody
文献摘要：
Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quanti-tatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fraction-ated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor ac-counting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.
文献关键词：
中图分类号：
作者姓名：
Xinling Cui;Wei Mi;Zhishang Hu;Xiaoyu Li;Bo Meng;Xinyuan Zhao;Xiaohong Qian;Tao Zhu;Wantao Ying
作者机构：
State Key Laboratory of Proteomics,Beijing Proteome Research Center,National Center for Protein Sciences(Beijing),Beijing Institute of Lifeomics,Beijing China;National Institute of Metrology,Center for Advanced Measurement Science,Beijing,China;National Institute of Metrology,Chemical Metrology&Analytical Science Division,Beijing,China;CanSino Bio Corporation Tianjin Key Laboratory of Recombinant Bacterial Recombination and Bacterial Vaccines,Tianjin,China
文献出处：
引用格式：
[1]Xinling Cui;Wei Mi;Zhishang Hu;Xiaoyu Li;Bo Meng;Xinyuan Zhao;Xiaohong Qian;Tao Zhu;Wantao Ying-.Global characterization of modifications to the charge isomers of IgG antibody)[J].药物分析学报（英文）,2022(01):156-163
A类：
Posttranslational,glycoforms,deamidation,glycoform
B类：
Global,characterization,modifications,charge,isomers,IgG,antibody,products,affect,their,stability,distribution,activity,are,thus,critical,quality,attribute,comprehensive,mapping,different,CIs,utmost,importance,challenging,We,intended,tatively,characterize,posttranslational,status,drugs,impact,heterogeneity,antibodies,were,fraction,by,strong,exchange,chromatography,verified,capillary,isoelectric,focusing,whole,column,imaging,detection,followed,stepwise,structural,three,levels,First,differences,between,explored,intact,protein,top,down,mass,spectrometry,approach,this,showed,Second,common,oxidation,glycosylation,identified,Peptide,nonuniform,among,In,total,detected,Finally,depth,analysis,glycan,variants,was,performed,through,enriched,glycopeptides,Qualitative,quantitative,analyses,demonstrated,dynamics,results,revealed,that,sialic,acid,counting,which,otherwise,missed,molecular,weight,This,study,provides,reference,method,control,biopharmaceutical
AB值：
0.513996
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