A New Approach for Identifying Positional Isomers of Glycans Cleaved from Monoclonal Antibodies

Overview

Journal Analyst

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2021 Jul 7

PMID 34231555

Citations 12

Authors

Irina Dyukova

Ahmed Ben Faleh

Stephan Warnke

Natalia Yalovenko

Vasyl Yatsyna

Priyanka Bansal

Thomas R Rizzo

Affiliations

Soon will be listed here.

Abstract

Glycosylation patterns in monoclonal antibodies (mAbs) can vary significantly between different host cell types, and these differences may affect mAbs safety, efficacy, and immunogenicity. Recent studies have demonstrated that glycan isomers with the terminal galactose position on either the Man α1-3 arm or the Man α1-6 arm have an impact on the effector functions and dynamic structure of mAbs. The development of a robust method to distinguish positional isomers of glycans is thus critical to guarantee mAb quality. In this work, we apply high-resolution ion mobility combined with cryogenic infrared spectroscopy to distinguish isomeric glycans with different terminal galactose positions, using G1F as an example. Selective enzymatic synthesis of the G1(α1-6)F isomer allows us to assign the peaks in the arrival-time distributions and the infrared spectra to their respective isomeric forms. Moreover, we demonstrate the impact of the host cell line (CHO and HEK-293) on the IgG G1F gycan profile at the isomer level. This work illustrates the potential of our approach for glycan analysis of mAbs.

Citing Articles

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Using Hadamard Transform Multiplexed IR Spectroscopy Together with a Segmented Ion Trap for the Identification of Mobility-Selected Isomers.

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PMID: 37307499 PMC: 10308330. DOI: 10.1021/acs.analchem.3c01340.

New Approach for the Identification of Isobaric and Isomeric Metabolites.

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Enhancing the Depth of Analyses with Next-Generation Ion Mobility Experiments.

Zercher B, Gozzo T, Wageman A, Bush M Annu Rev Anal Chem (Palo Alto Calif). 2023; 16(1):27-48.

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Multistage Ion Mobility Spectrometry Combined with Infrared Spectroscopy for Glycan Analysis.

Bansal P, Ben Faleh A, Warnke S, Rizzo T J Am Soc Mass Spectrom. 2023; 34(4):695-700.

PMID: 36881006 PMC: 10080682. DOI: 10.1021/jasms.2c00361.

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