High-throughput glycosylation analysis of therapeutic immunoglobulin G by capillary gel electrophoresis using a DNA analyzer

MAbs. 2014 Jan-Feb;6(1):185-96. doi: 10.4161/mabs.26712.

Abstract

The Fc glycosylation of therapeutic antibodies is crucial for their effector functions and their behavior in pharmacokinetics and pharmacodynamics. To monitor the Fc glycosylation in bioprocess development and characterization,high-throughput techniques for glycosylation analysis are needed. Here, we describe the development of a largely automated high-throughput glycosylation profiling method with multiplexing capillary-gel-electrophoresis (CGE) with laser induced fluorescence (LIF) detection using a DNA analyzer. After PNGaseF digestion, the released glycans were labeled with 9-aminopyrene-1,3,6-trisulfonic acid (APTS) in 96-well plates, which was followed by the simultaneous analysis of up to 48 samples. The peak assignment was conducted by HILIC-UPLC-MS/MS of the APTS-labeled glycans combined with peak fractionation and subsequent CGE-LIF analysis of the MS-characterized fractions. Quantitative data evaluation of the various IgG glycans was performed automatically using an in-house developed software solution. The excellent method accuracy and repeatability of the test system was verified by comparison with two UPLC-based methods for glycan analysis. Finally, the practical value of the developed method was demonstrated by analyzing the antibody glycosylation profiles from fermentation broths after small scale protein A purification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Electrophoresis, Capillary
  • Fluorescent Dyes / chemistry*
  • Glycosylation
  • Immunoglobulin G / chemistry*
  • Polysaccharides / chemistry*
  • Pyrenes / chemistry
  • Sequence Analysis, DNA / instrumentation*
  • Software*

Substances

  • 1-aminopyrene-3,6,8-trisulfonic acid
  • Antibodies, Monoclonal
  • Fluorescent Dyes
  • Immunoglobulin G
  • Polysaccharides
  • Pyrenes