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3


Advancing Effective Glycan Analysis Melissa Sherman* PhD, CEO,


MOBILion Systems Inc, Chadds Ford, Pennsylvania, USA Lance Wells PhD,


Georgia Research Alliance Distinguished Investigator, Professor of Biochemistry and Molecular Biology, Director of integrated life sciences, and co-director of the Thermo Fisher appointed Center of Excellence in Glycoproteomics at the CCRC at the University of Georgia, Athens, Georgia, USA


Mike Tiemeyer PhD,


Distinguished Research Professor of Biochemistry and Molecular Biology, Co-director of the Thermo Fisher appointed Center of Excellence in Glycoproteomics at the University of Georgia, and Co-Director of the Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA


Corresponding author* Abstract


Researchers are paying increasing attention to a critically important class of biomolecules: glycans. Although less studied than other major building blocks of life - proteins, lipids, and nucleic acids - complex and diverse glycans are essential to life and are omnipresent in organisms from archaea to humans [1].


Recent advances in glycoscience have shone new light on glycans and their role as key metabolic, structural, and physical components in biological structures. The potential of glycoengineering has been established, perhaps most significantly, in therapeutic antibody development.


This article outlines examples of the role glycans play clinically, the challenges of glycan analysis, summarises the tools available to elucidate their intricate structures, and presents data comparing traditional LC-MS workflows with the emerging technique of high-resolution ion mobility (HRIM) spectroscopy.


B


Glycans, Glycoengineering and Drug Development


With knowledge of glycobiology expanding, the tremendous importance of the function of glycans in many branches of life science [2] including vital fields such as oncology [3], immunology [4], and infectious disease [5] is being elucidated. Moreover, developments in glycan analysis have coincided with an increased capacity to control glycosylation of specific biomolecules. Known as glycoengineering, this process involves manipulating glycosylation patterns, either by genetic modulation of specific glycosyltransferases or through chemical manipulation of glycoconjugates after biosynthesis [6].


Differences in glycosylation have been shown to affect therapeutic monoclonal antibody (mAb) activity in a number of


A


Figure 1: A) Arrangement of interspersed RF and DC electrodes on PCBs which enable trapping and manipulation of ions around corners along a serpentine path. B) Trapped ions traverse with the traveling wave created by the electrodes and separate based on size and shape.


ways [7,8]. As a key example, reduction or elimination of fucose monosaccharides from Fc domain glycans (also known as defucosylation) has been repeatedly shown to increase antibody-dependent cellular cytotoxicity (ADCC). Defucosylating antibody constructs leads to higher


activation of natural killer (NK) as well as other immune cells. This, in turn, causes greater ADCC where the therapeutic mAb binds, including cancer cells [12,13]. Genentech (South San Francisco, California, USA) applied this strategy to develop Gazyva (obinutuzumab) to succeed its


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