Too often the glycosylation modifications to proteins have been overlooked as “being too hard” to analyse. Increasingly however, these extensive protein modifications are being found to have crucial and varied influence on, dare I say, most biological molecular interactions.
The analysis of the glycan structures, their sites on the proteins and their relative abundance is now able to be achieved using much the same tools as are used in proteomics analysis; at the single protein, protein complex and potentially at high throughput glycoprotein detailed characterisation [1,2,3,6,10]. Although improvements in informatics are still required, the current methods that we use for glycomics (the analysis of the sequence and linkage of glycan structures) and glycoproteomics (the analysis of the glycan composition, site occupation, and abundance of intact glycopeptides) are now able to address most biological research questions.
The availability of this glycoanalytical capability is in fact, increasingly being applied to a range of biological systems with the resultant increase in our understanding of biomolecular interaction mechanisms [4,8,9,12] as well as producing new biomarkers, imaging agents and drug targets. In this regard, the importance of the glycosylation of different experimental models used to investigate biomolecular questions will be emphasised. The talk will also present new data on some examples of where a knowledge of the glycan structural changes that have been observed to occur under biological perturbations such as cancer and pain can be usefully targeted by sensitive microscopic and spectroscopic detection approaches [5,7,11] at the biopsy, cell and tissue level.
- Pia H. Jensen et al (2012) Structural Analysis of N- and O- glycans released from glycoproteins. Nature Protocols. 7 , 1299.
- Daniel Kolarich, et al (2012) Determination of site specific glycan heterogeneity on glycoproteins. Nature Protocols. 7, 1285.
- Benjamin Parker et al (2013) Site-specific glycan-peptide analysis for determination of N-glycoproteome heterogeneity. J. Proteome Res. 12:5791.
- Ian Loke et al (2015) Complementary LC-MS/MS-Based N-Glycan, N-Glycopeptide, and Intact N-Glycoprotein Profiling Reveals Unconventional Asn71-Glycosylation of Human Neutrophil Cathepsin G. Biomolecules 5:1832
- Arun Everest-Dass, et al (2016). N-glycan MALDI Imaging Mass Spectrometry on Formalin-Fixed Paraffin-Embedded Tissue Enables the Delineation of Ovarian Cancer Tissues. Molecular Cell Proteomics 15:3003
- Ling Lee et al (2016) Towards Automated N-glycopeptide identification in glycoproteomics. J. Proteome Res. 15:3904
- Nima Sayyadi et al (2016). Sensitive Time-Gated Immunoluminescence Detection of Prostate Cancer Cells Using a TEGylated Europium Ligand. Analytical Chemistry. 88:9564
- Phil Bokiniec et al (2017) Polysialic Acid Regulates Sympathetic Outflow By Facilitating Information Transfer Within The Nucleus Of The Solitary Tract. J.Neuroscience, 37:6558
- Merrina Anugraham et al (2017) Tissue glycomics distinguish tumour sites in women with advanced serous adenocarcinoma. Mol Oncol. 11:1595.
- Arun Everest-Dass et al (2018) Human disease glycomics: technology advances enabling analysis of specific glycan structures on proteins – Part 1&2. Expert Reviews in Proteomics 15:165
- Nicole Cordina et al (2018) Reduced background autofluorescence for cell imaging using nanodiamonds and lanthanide chelates. Scientific Reports 8:4521.
- David De Oliveira et al (2019) Human glycan expression patterns influence Group A streptococcal colonization of epithelial cells The FASEB Journal (accepted)