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J Proteome Res. 2018 Dec 7;17(12):4097-4112. doi: 10.1021/acs.jproteome.8b00515. Epub 2018 Oct 25.

Current Technologies for Complex Glycoproteomics and Their Applications to Biology/Disease-Driven Glycoproteomics.

Author information

1
Biotechnology Research Institute for Drug Discovery , National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono , Tsukuba , Ibaraki 305-8568 , Japan.
2
Copenhagen Center for Glycomics , University of Copenhagen , Blegdamsvej 3 , Copenhagen 2200 , Denmark.
3
Center for Biomarker Discovery and Translation , Johns Hopkins University , 400 North Broadway , Baltimore , Maryland 21205 , United States.
4
Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education) , Shanghai Jiao Tong University , 800 Dong Chuan Road , Minhang , Shanghai 200240 , P.R. China.

Abstract

Glycoproteomics is an important recent advance in the field of glycoscience. In glycomics, glycan structures are comprehensively analyzed after glycans are released from glycoproteins. However, a major limitation of glycomics is the lack of insight into glycoprotein functions. The Biology/Disease-driven Human Proteome Project has a particular focus on biological and medical applications. Glycoproteomics technologies aimed at obtaining a comprehensive understanding of intact glycoproteins, i.e., the kind of glycan structures that are attached to particular amino acids and proteins, have been developed. This Review focuses on the recent progress of the technologies and their applications. First, the methods for large-scale identification of both N- and O-glycosylated proteins are summarized. Next, the progress of analytical methods for intact glycopeptides is outlined. MS/MS-based methods were developed for improving the sensitivity and speed of the mass spectrometer, in parallel with the software for complex spectrum assignment. In addition, a unique approach to identify intact glycopeptides using MS1-based accurate masses is introduced. Finally, as an advance of glycomics, two approaches to provide the spatial distribution of glycans in cells are described, i.e., MS imaging and lectin microarray. These methods allow rapid glycomic profiling of different types of biological samples and thus facilitate glycoproteomics.

KEYWORDS:

glycan spatial distribution; glycome mapping; glycoprotein; glycoproteome; glycosylation site-mapping; lectin microarray; mass spectrometry; protein glycosylation; site-specific glycan analysis

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