首页|"Small is beautiful"-Examining reliable determination of low-abundant therapeutic antibody glycovariants

"Small is beautiful"-Examining reliable determination of low-abundant therapeutic antibody glycovariants

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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
Glycans associated with biopharmaceutical drugs play crucial roles in drug safety and efficacy,and therefore,their reliable detection and quantification is essential.Our study introduces a multi-level quantification approach for glycosylation analysis in monoclonal antibodies(mAbs),focusing on minor abundant glycovariants.Mass spectrometric data is evaluated mainly employing open-source software tools.Released N-glycan and glycopeptide data form the basis for integrating information across different structural levels up to intact glycoproteins.Comprehensive comparison showed that indeed,variations across structural levels were observed especially for minor abundant species.Utilizing modification finder(MoFi),a tool for annotating mass spectra of intact proteins,we quantify isobaric glycosylation variants at the intact protein level.Our workflow's utility is demonstrated on NISTmAb,rituximab and adalimumab,profiling their minor abundant variants for the first time across diverse structural levels.This study enhances understanding and accessibility in glycosylation analysis,spotlighting minor abundant glycovariants in therapeutic antibodies.

GlycosylationMass spectrometryMonoclonal antibodiesAbundance profilingMinor glycovariantsMulti-level analysisData integration

Katharina Böttinger、Christof Regl、Veronika Schäpertöns、Erdmann Rapp、Therese Wohlschlager、Christian G.Huber

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Department of Biosciences and Medical Biology,Bioanalytical Research Labs,University of Salzburg,Salzburg,5020,Austria

Center for Tumorbiology and Immunology(CTBI),University of Salzburg,Salzburg 5020,Austria

glyXera GmbH,Magdeburg,Sachsen-Anhalt,39014,Germany

Max Planck Institute for Dynamics of Complex Technical Systems,Magdeburg,39106,Germany

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2024

10.1016/j.jpha.2024.100982

药物分析学报(英文)
西安交通大学

药物分析学报(英文)

影响因子：0.244
ISSN：2095-1779
年,卷(期)：2024.14(10)