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Strategies for the profiling, characterisation and detailed structural analysis of N-linked oligosaccharides

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Abstract

Many post-translational modifications, including glycosylation, are pivotal for the structural integrity, location and functional activity of glycoproteins. Sub-populations of proteins that are relocated or functionally changed by such modifications can change resting proteins into active ones, mediating specific effector functions, as in the case of monoclonal antibodies. To ensure safe and efficacious drugs it is essential to employ appropriate robust, quantitative analytical strategies that can (i) perform detailed glycan structural analysis, (ii) characterise specific subsets of glycans to assess known critical features of therapeutic activities (iii) rapidly profile glycan pools for at-line monitoring or high level batch to batch screening. Here we focus on these aspects of glycan analysis, showing how state-of-the-art technologies are required at all stages during the production of recombinant glycotherapeutics. These data can provide insights into processing pathways and suggest markers for intervention at critical control points in bioprocessing and also critical decision points in disease and drug monitoring in patients. Importantly, these tools are now enabling the first glycome/genome studies in large populations, allowing the integration of glycomics into other ‘omics platforms in a systems biology context.

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Abbreviations

2AB:

2-aminobenzamide

ADCC:

Antibody dependent cell cytotoxicity

APTS:

8-aminopyrene-1,3,6-trisulfonate

BEH:

Ethylene Bridged Hybrid

CE-LIF:

Capillary electrophoresis with laser induced fluorescence

CQA:

Critical quality attribute

EMA:

European Medicines Agency

EPO:

Erythropoietin

ESI-MS:

Electrospray ionization – mass spectrometry

FDA:

Food and Drug Administration

FLD:

Fluorescence detector

FUT6 and FUT8:

Fucosyltransferase 6 and 8

GWAS:

Genome-wide association study

HILIC:

Hydrophilic interaction chromatography

HNF1α:

Hepatocyte nuclear factor 1α

HPLC:

High performance liquid chromatography

IgG:

Immunoglobulin G

LC-MS:

Liquid chromatography – mass spectrometry

MALDI:

Matrix-assisted laser desorption/ionization

NMR:

Nuclear magnetic resonance

PAT:

Process analytical technology

PGC:

Porous graphitized carbon

RP:

Reversed phase

SNPs:

Single nucleotide polymorphisms

UPLC:

Ultra performance liquid chromatography

WAX:

Weak anion exchange

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TT acknowledges funding from Science Foundation Ireland (Reproductive Biology Research Cluster (RBRC)) [grant number 07/SRC/B1156], BA acknowledges funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement 215536 (EuroGlycoArrays), MAD acknowledges funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement 259869 (GlycoBioM). The authors thank Prof. Johannis P. Kamerling for fruitful discussions.

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Authors and Affiliations

  1. NIBRT Glycobiology Laboratory, NIBRT - The National Institute for Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Co. Dublin, Ireland

    Tharmala Tharmalingam, Barbara Adamczyk, Margaret A. Doherty & Pauline M. Rudd

  2. Ludger Ltd., Culham Science Centre, Oxfordshire, OX14 3EB, UK

    Louise Royle

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  1. Tharmala Tharmalingam
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  2. Barbara Adamczyk
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  3. Margaret A. Doherty
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  4. Louise Royle
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  5. Pauline M. Rudd
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Correspondence to Pauline M. Rudd.

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Tharmalingam, T., Adamczyk, B., Doherty, M.A. et al. Strategies for the profiling, characterisation and detailed structural analysis of N-linked oligosaccharides. Glycoconj J 30, 137–146 (2013). https://doi.org/10.1007/s10719-012-9443-9

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  • DOI: https://doi.org/10.1007/s10719-012-9443-9

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