Glycoconjugate Journal

, Volume 30, Issue 2, pp 137–146 | Cite as

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

  • Tharmala Tharmalingam
  • Barbara Adamczyk
  • Margaret A. Doherty
  • Louise Royle
  • Pauline M. Rudd
Article

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.

Keywords

Glycosylation Glycan analysis High throughput Glycoprofiling Database 

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

Notes

Funding

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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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Tharmala Tharmalingam
    • 1
  • Barbara Adamczyk
    • 1
  • Margaret A. Doherty
    • 1
  • Louise Royle
    • 2
  • Pauline M. Rudd
    • 1
  1. 1.NIBRT Glycobiology Laboratory, NIBRT - The National Institute for Bioprocessing Research and TrainingCo. DublinIreland
  2. 2.Ludger Ltd., Culham Science CentreOxfordshireUK

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