M. Osman Sheikh
Chantelle J. Capicciotti
Stéphanie Olivier-Van Stichelen- 1Discovery Science Division, Amicus Therapeutics, Inc., Philadelphia, PA, United States
- 2Departments of Chemistry, Biomedical and Molecular Sciences, and Surgery, Queen’s University, Kingston, ON, Canada
- 3Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, United States
Editorial on the Research Topic
Glycotherapeutics: Design, synthesis, function and biomedical application of agents emerging from glycochemistry and glycobiology
Post-translational glycosylation is a non-template driven process for the addition of carbohydrates, or glycans, to biomolecules such as protein and lipids. It is well recognized that glycosylation impacts many cellular processes including, but not limited to, protein folding, trafficking, receptor binding, signaling, inflammation, and cell-to-cell/matrix adhesion (Varki 2017). Additionally, glycans can be used in the targeting of drugs in diseases such as cancer (Diniz et al., 2022) and lysosomal storage disorders (Do et al., 2019) as well as modulating pharmacokinetics and immunogenicity of therapeutic proteins and antibodies (Liu 2015; Archer et al., 2022; Dammen-Brower et al., 2022).
The goal of this Research Topic was to assemble a collection of articles highlighting recent advancements pertaining to diagnostic tools and therapeutics utilizing multidisciplinary approaches in glycobiology and glycochemistry. Collectively, four articles submitted by 21 experts in glycoscience were peer-reviewed and accepted for publication in this Research Topic to emphasize the importance of glycans in human health and disease, in addition to presenting rapidly evolving technologies used in the analysis of carbohydrate-modified molecules and the enzymes that synthesize or degrade them.
A review article by Loaeza-Reyes et al. provides a comprehensive overview of protein N-linked and O-linked glycosylation and their implications in cardiovascular function and disease, including an analysis of cardiovascular disease risk factors associated with aberrant N-glycosylation and the dynamic role of the O-GlcNAc modification in inflammation. With more than 7,800 proteins modified in humans, O-GlcNAcylation is a critical modulator of signaling pathways in health and diseases (Wulff-Fuentes et al., 2021). Taking an analytical approach, Burt et al. provide a review of this dynamic modification and strategies to elucidate O-GlcNAc-modified proteins using high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The glycosidic bond between GlcNAc and serine or threonine residues is inherently labile, thus careful MS fragmentation strategies must be taken into consideration in order to accurately detect O-glycopeptides. While the mass spectrometer cannot discern the two HexNAc stereoisomers, GlcNAc and GalNAc, the authors summarize efforts in the literature to accurately identify the correct stereoisomers based on the ratio of fragment ions produced from the respective glycans. Additionally, Mukherjee et al. contributed a review article describing synthetic approaches to stereoselective chemical O-glycosylation reactions, which can be extremely challenging. This valuable summary of methods will aid the synthetic chemist in deriving a strategy for synthesizing target glycans with defined glycosidic linkages, including 1,2-cis, 1,2-trans and 2-deoxy-glycosides. Finally, a research article by Howlader et al. studied human neuraminidase enzymes and their roles in transmigration using an in vitro system. Here, the authors investigated the pharmacological inhibition of the NEU1, NEU3, and NEU4 isoenzymes. They propose these enzymes are positive regulators of transmigration and are potential targets for anti-inflammatory approaches.
In summary, within this Research Topic we sought to highlight the recent advancements in Glycoscience and how they can be utilized for therapeutic approaches to human diseases. We hope this collection of articles will be of interest to the broader scientific community and facilitate further discussion.
Author contributions
All authors listed have made a substantial, direct, and intellectual contribution to this editorial and approved it for publication.
Funding
This work was supported in part by: The National Institute of Child Health and Human Development and the Medical College of Wisconsin (SOVS); Natural Sciences and Engineering Research Council of Canada (NSERC) (CC).
Acknowledgments
We deeply thank all the authors and reviewers who have participated in this Research Topic.
Conflict of interest
MS was employed by the Amicus Therapeutics Inc. and holds equity in the company in the form of stock-based compensation.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
Archer, E. J., Gonzalez, J. C., Ghosh, D., Mellins, E. D., and Wang, T. T. (2022). Harnessing IgG Fc glycosylation for clinical benefit. Curr. Opin. Immunol. 77, 102231. doi:10.1016/j.coi.2022.102231
Dammen-Brower, K., Epler, P., Zhu, S., Bernstein, Z. J., Stabach, P. R., Braddock, D. T., et al. (2022). Strategies for glycoengineering therapeutic proteins. Front. Chem. 10, 863118. doi:10.3389/fchem.2022.863118
Diniz, F., Coelho, P., Duarte, H. O., Sarmento, B., Reis, C. A., and Gomes, J. (2022). Glycans as Targets for Drug Delivery in Cancer, 14. Cancers (Basel).
Do, H. V., Khanna, R., and Gotschall, R. (2019). Challenges in treating pompe disease: An industry perspective. Ann. Transl. Med. 7, 291. doi:10.21037/atm.2019.04.15
Liu, L. (2015). Antibody glycosylation and its impact on the pharmacokinetics and pharmacodynamics of monoclonal antibodies and Fc-fusion proteins. J. Pharm. Sci. 104, 1866–1884. doi:10.1002/jps.24444
Keywords: glycans, glycomics, chemical biology, glycoengineering, carbohydrates
Citation: Sheikh MO, Capicciotti CJ and Olivier-Van Stichelen S (2022) Editorial: Glycotherapeutics: Design, synthesis, function and biomedical application of agents emerging from glycochemistry and glycobiology. Front. Mol. Biosci. 9:1012485. doi: 10.3389/fmolb.2022.1012485
Received: 05 August 2022; Accepted: 25 August 2022;
Published: 08 September 2022.
Edited by:
Matthew P. DeLisa, Cornell University, United StatesReviewed by:
Mattheos Koffas, Rensselaer Polytechnic Institute, United StatesCopyright © 2022 Sheikh, Capicciotti and Olivier-Van Stichelen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: M. Osman Sheikh, osman.sheikh1@gmail.com; Chantelle J. Capicciotti, c.capicciotti@queensu.ca; Stéphanie Olivier-Van Stichelen, solivier@mcw.edu