Glycan array

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Glycan arrays, [1] like that offered by the Consortium for Functional Glycomics (CFG), National Center for Functional Glycomics (NCFG) and Z Biotech, LLC, contain carbohydrate compounds that can be screened with lectins, antibodies or cell receptors to define carbohydrate specificity and identify ligands. Glycan array screening works in much the same way as other microarray that is used for instance to study gene expression DNA microarrays or protein interaction Protein microarrays.

Glycan arrays are composed of various oligosaccharides and/or polysaccharides immobilised on a solid support in a spatially-defined arrangement. [2] This technology provides the means of studying glycan-protein interactions in a high-throughput environment. These natural or synthetic (see carbohydrate synthesis) glycans are then incubated with any glycan-binding protein such as lectins, cell surface receptors or possibly a whole organism such as a virus. Binding is quantified using fluorescence-based detection methods. Certain types of glycan microarrays can even be re-used for multiple samples using a method called Microwave Assisted Wet-Erase. [3]

Applications

Glycan arrays have been used to characterize previously unknown biochemical interactions. For example, photo-generated glycan arrays have been used to characterize the immunogenic properties of a tetrasaccharide found on the surface of anthrax spores. [4] Hence, glycan array technology can be used to study the specificity of host-pathogen interactions. [5]

Early on, glycan arrays were proven useful in determining the specificity of the Hemagglutinin (influenza) of the Influenza A virus binding to the host and distinguishing across different strains of flu (including avian from mammalian). This was shown with CFG arrays [6] as well as customised arrays. [7] Cross-platform benchmarks led to highlight the effect of glycan presentation and spacing on binding. [8]

Glycan arrays are possibly combined with other techniques such as Surface Plasmon Resonance (SPR) to refine the characterisation of glycan-binding. For example, this combination led to demonstrate the calcium-dependent heparin binding of Annexin A1 that is involved in several biological processes including inflammation, apoptosis and membrane trafficking. [9]

Related Research Articles

Glycomics is the comprehensive study of glycomes, including genetic, physiologic, pathologic, and other aspects. Glycomics "is the systematic study of all glycan structures of a given cell type or organism" and is a subset of glycobiology. The term glycomics is derived from the chemical prefix for sweetness or a sugar, "glyco-", and was formed to follow the omics naming convention established by genomics and proteomics.

<span class="mw-page-title-main">Microarray</span> Small-scale two-dimensional array of samples on a solid support

A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of biological interactions. It is a two-dimensional array on a solid substrate—usually a glass slide or silicon thin-film cell—that assays (tests) large amounts of biological material using high-throughput screening miniaturized, multiplexed and parallel processing and detection methods. The concept and methodology of microarrays was first introduced and illustrated in antibody microarrays by Tse Wen Chang in 1983 in a scientific publication and a series of patents. The "gene chip" industry started to grow significantly after the 1995 Science Magazine article by the Ron Davis and Pat Brown labs at Stanford University. With the establishment of companies, such as Affymetrix, Agilent, Applied Microarrays, Arrayjet, Illumina, and others, the technology of DNA microarrays has become the most sophisticated and the most widely used, while the use of protein, peptide and carbohydrate microarrays is expanding.

<span class="mw-page-title-main">Glycome</span> Complete set of all sugars, free or bound, in an organism.

A glycome is the entire complement or complete set of all sugars, whether free or chemically bound in more complex molecules, of an organism. An alternative definition is the entirety of carbohydrates in a cell. The glycome may in fact be one of the most complex entities in nature. "Glycomics, analogous to genomics and proteomics, is the systematic study of all glycan structures of a given cell type or organism" and is a subset of glycobiology.

<span class="mw-page-title-main">Consortium for Functional Glycomics</span> Glycomics research initiative

The Consortium for Functional Glycomics (CFG) is a large research initiative funded in 2001 by a glue grant from the National Institute of General Medical Sciences (NIGMS) to “define paradigms by which protein-carbohydrate interactions mediate cell communication”. To achieve this goal, the CFG studies the functions of:

Defined in the narrowest sense, glycobiology is the study of the structure, biosynthesis, and biology of saccharides that are widely distributed in nature. Sugars or saccharides are essential components of all living things and aspects of the various roles they play in biology are researched in various medical, biochemical and biotechnological fields.

<span class="mw-page-title-main">Lectin</span> Carbohydrate-binding protein

Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in recognition at the cellular and molecular level and play numerous roles in biological recognition phenomena involving cells, carbohydrates, and proteins. Lectins also mediate attachment and binding of bacteria, viruses, and fungi to their intended targets.

An oligosaccharide is a saccharide polymer containing a small number of monosaccharides. Oligosaccharides can have many functions including cell recognition and cell adhesion.

<span class="mw-page-title-main">Hemagglutinin esterase</span> Glycoprotein present in some enveloped viruses

Hemagglutinin esterase (HEs) is a glycoprotein that certain enveloped viruses possess and use as an invading mechanism. HEs helps in the attachment and destruction of certain sialic acid receptors that are found on the host cell surface. Viruses that possess HEs include influenza C virus, toroviruses, and coronaviruses of the subgenus Embecovirus. HEs is a dimer transmembrane protein consisting of two monomers, each monomer is made of three domains. The three domains are: membrane fusion, esterase, and receptor binding domains.

The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate portion of a glycoconjugate, such as a glycoprotein, glycolipid, or a proteoglycan, even if the carbohydrate is only an oligosaccharide. Glycans usually consist solely of O-glycosidic linkages of monosaccharides. For example, cellulose is a glycan composed of β-1,4-linked D-glucose, and chitin is a glycan composed of β-1,4-linked N-acetyl-D-glucosamine. Glycans can be homo- or heteropolymers of monosaccharide residues, and can be linear or branched.

Glycoconjugates are the classification family for carbohydrates – referred to as glycans – which are covalently linked with chemical species such as proteins, peptides, lipids, and other compounds. Glycoconjugates are formed in processes termed glycosylation.

Siglecs(Sialic acid-binding immunoglobulin-type lectins) are cell surface proteins that bind sialic acid. They are found primarily on the surface of immune cells and are a subset of the I-type lectins. There are 14 different mammalian Siglecs, providing an array of different functions based on cell surface receptor-ligand interactions.

Richard D. Cummings is an American biochemist who is the S. Daniel Abraham Professor of Surgery at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, Massachusetts. He also the chief of the division of surgical sciences within the department of surgery. He is the director of the Harvard Medical School Center for Glycoscience, director of the National Center for Functional Glycomics, and also founder of the Glycomics Core at BIDMC. As of 2018 Cummings is also the scientific director of the Feihi Nutrition Laboratory at BIDMC. Before moving to BIDMC/HMS, Cummings was the William Patterson Timmie Professor and chair of the department of biochemistry at Emory University School of Medicine in Atlanta, Georgia from 2006 to 2015. At Emory, Cummings was a founder in 2007 of the Emory Glycomics Center.

<span class="mw-page-title-main">Hemagglutinin</span>

In molecular biology, hemagglutinins are receptor-binding membrane fusion glycoproteins produced by viruses in the Paramyxoviridae and Orthomyxoviridae families. Hemagglutinins are responsible for binding to receptors on red blood cells to initiate viral attachment and infection. The agglutination of red cells occurs when antibodies on one cell bind to those on others, causing amorphous aggregates of clumped cells.

Translational glycobiology or applied glycobiology is the branch of glycobiology and glycochemistry that focuses on developing new pharmaceuticals through glycomics and glycoengineering. Although research in this field presents many difficulties, translational glycobiology presents applications with therapeutic glycoconjugates, with treating various bone diseases, and developing therapeutic cancer vaccines and other targeted therapies. Some mechanisms of action include using the glycan for drug targeting, engineering protein glycosylation for better efficacy, and glycans as drugs themselves.

<span class="mw-page-title-main">National Center for Functional Glycomics</span>

The National Center for Functional Glycomics is an organization that is focused on the development of technology development in glycosciences. They are specifically focused on glycan analysis and molecular mechanisms of glycan recognition by proteins important in human biology and disease. The center was established at Emory University in 2013 with $5.5 million funding by National Institutes of Health under the leadership of Richard D. Cummings. The center moved to Harvard University in September 2015 and is currently located at Beth Israel Deaconess Medical Center in Boston Massachusetts. The center is affiliated with the Consortium for Functional Glycomics.

The Minimum Information Required About a Glycomics Experiment (MIRAGE) initiative is part of the Minimum Information Standards and specifically applies to guidelines for reporting on a glycomics experiment. The initiative is supported by the Beilstein Institute for the Advancement of Chemical Sciences. The MIRAGE project focuses on the development of publication guidelines for interaction and structural glycomics data as well as the development of data exchange formats. The project was launched in 2011 in Seattle and set off with the description of the aims of the MIRAGE project.

<span class="mw-page-title-main">Symbol Nomenclature For Glycans</span>

The Symbol Nomenclature For Glycans (SNFG) is a community-curated standard for the depiction of simple monosaccharides and complex carbohydrates (glycans) using various colored-coded, geometric shapes, along with defined text additions. It is hosted by the National Center for Biotechnology Information at the NCBI-Glycans Page. It is curated by an international groups of researchers in the field that are collectively called the SNFG Discussion Group. The overall goal of the SNFG is to:

  1. Facilitate communications and presentations of monosaccharides and glycans for researchers in the Glycosciences, and for scientists and students less familiar with the field.
  2. Ensure uniform usage of the nomenclature in the literature, thus helping to ensure scientific accuracy in journal and online publications.
  3. Continue to develop the SNFG and its applications to aid wider use by the scientific community.

Ten Feizi is a Turkish Cypriot/British molecular biologist who is Professor and Director of the Glycosciences Laboratory at Imperial College London. Her research considers the structure and function of glycans. She was awarded the Society for Glycobiology Rosalind Kornfeld award in 2014. She was also awarded the Fellowship of the Academy of Medical Sciences in 2021.

<span class="mw-page-title-main">Glycan-protein interactions</span> Class of biological intermolecular interactions

Glycan-Protein interactions represent a class of biomolecular interactions that occur between free or protein-bound glycans and their cognate binding partners. Intramolecular glycan-protein (protein-glycan) interactions occur between glycans and proteins that they are covalently attached to. Together with protein-protein interactions, they form a mechanistic basis for many essential cell processes, especially for cell-cell interactions and host-cell interactions. For instance, SARS-CoV-2, the causative agent of COVID-19, employs its extensively glycosylated spike (S) protein to bind to the ACE2 receptor, allowing it to enter host cells. The spike protein is a trimeric structure, with each subunit containing 22 N-glycosylation sites, making it an attractive target for vaccine search.

Nicki Packer FRSC is a distinguished professor of glycoproteomics in the School of Natural Sciences at Macquarie University and principal research leader at Griffith University's Institute for Glycomics. Packer is a Fellow of the Royal Society of Chemistry and in 2021 received the Distinguished Achievement in Proteomic Sciences Award from the Human Proteome Organization. Her research focuses on biological functional of glycoconjugates by linking glycomics with proteomics and bioinformatics.

References

  1. ↑ Carroll GT, Wang D, Turro NJ, Koberstein JT (2006). "Photochemical Micropatterning of Carbohydrates on a Surface". Langmuir. 22: 2899–2905. doi:10.1021/la0531042.
  2. ↑ Oyelaran O, Gildersleeve JC (Oct 2009). "Glycan arrays: recent advances and future challenges". Curr Opin Chem Biol. 13 (4): 406–413. doi:10.1016/j.cbpa.2009.06.021. PMC   2749919 . PMID   19625207.
  3. ↑ Mehta, Akul Y; Tilton, Catherine A; Muerner, Lukas; von Gunten, Stephan; Heimburg-Molinaro, Jamie; Cummings, Richard D (14 November 2023). "Reusable glycan microarrays using a microwave assisted wet-erase (MAWE) process". Glycobiology. doi:10.1093/glycob/cwad091. PMID   37962922.
  4. ↑ Wang D, Carroll GT, Turro NJ, Koberstein JT, Kováč P, Saksena R, Adamo R, Herzenberg LA, Herzenberg LA, Steinman L (2007). "Photogenerated glycan arrays identify immunogenic sugar moieties of Bacillus anthracis exosporium". Proteomics. 7: 180–184. doi: 10.1002/pmic.200600478 .
  5. ↑ Geissner A, Anish C, Seeberger PH (Feb 2014). "Glycan arrays as tools for infectious disease research". Curr Opin Chem Biol. 18: 38–45. doi:10.1016/j.cbpa.2013.11.013. PMID   24534751.
  6. ↑ Stevens J, Blixt O, Tumpey TM, Taubenberger JK, Paulson JC, Wilson IA (Apr 2006). "Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus". Science. 312 (5772): 404–410. Bibcode:2006Sci...312..404S. doi:10.1126/science.1124513. PMID   16543414.
  7. ↑ Childs RA, Palma AS, Wharton S, Matrosovich T, Liu Y, Chai W, Campanero-Rhodes MA, Zhang Y, Eickmann M, Kiso M, Hay A, Matrosovich M, Feizi T (Sep 2009). "Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray". Nat Biotechnol. 27 (9): 797–799. doi:10.1038/nbt0909-797. PMC   3771066 . PMID   19741625.
  8. ↑ Wang L, Cummings RD, Smith DF, Huflejt M, Campbell CT, Gildersleeve JC, Gerlach JQ, Kilcoyne M, Joshi L, Serna S, Reichardt NC, Parera Pera N, Pieters RJ, Eng W, Mahal LK (Jun 2014). "Cross-platform comparison of glycan microarray formats". Glycobiology. 24 (6): 507–17. doi:10.1093/glycob/cwu019. PMC   4001710 . PMID   24658466.
  9. ↑ Horlacher T, Noti C, de Paz JL, Bindschädler P, Hecht ML, Smith DF, Fukuda MN, Seeberger PH (Apr 2011). "Characterization of annexin A1 glycan binding reveals binding to highly sulfated glycans with preference for highly sulfated heparan sulfate and heparin". Biochemistry. 50 (13): 2650–9. doi:10.1021/bi101121a. PMC   3068229 . PMID   21370880.
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