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Glycobiology Overview

BioFiles 2007, 2.1, 1.

BioFiles 2007, 2.1, 1.

Introduction

Glycans are ubiquitous in nature, and their representation on cell surfaces is commonly called the glycome. Oligosaccharides and polysaccharides are responsible for much of the structural variation in biological systems and are generated by cells to serve as structural scaffolds, to regulate viscosity, and for energy storage. The carbohydrate moieties of cell surface glycoproteins and glycolipids function in cellular communication processes and physiological responses.1-4 Cell-surface glycoproteins and glycolipids provide anchors for intercellular adhesion, provide points of attachment for antibodies and other proteins, and function as receptor sites for bacteria and viral particles.5,6

Many intracellular processing events are disrupted environmentally or are the result of genomic abnormalities (congenital disorders of glycosylation; CDG) and result in disease states. Altered cell surface glycosylation patterns are associated with cellular differentiation, development, and viral infection, and are diagnostic in certain cancers,7 correlating to changes in the expression or localization of relevant glycosyltransferases. Multiple studies have evaluated the roles of glycoproteins and proteoglycans in tumor metastasis, angiogenesis, inflammatory cell migration, lymphocyte homeostasis, and congenital disorders of glycosylation. Oligosaccharides and competitive glycoconjugates are potential drug targets in infectious diseases, inflammation and cancer. Glycosylation of proteins and other bioactive molecules has been shown to increase solubility of hydrophobic molecules,8,9 alter uptake and residency time in vivo,10,11 and decrease antigenicity.12

The progress of glycomics in the biopharmaceutical industry is demonstrated by the development of drugs that manipulate carbohydrates and glycoproteins for therapeutic benefit. Research on glycosyl transferases to understand the role of carbohydrate interactions in cancerous cells is also likely to provide further opportunities for application of glycomics. Scientists observing cultured cells that correspond with solid tumors have found expressed glycoprotein antigens that may provide the basis for the development of serum-based biomarker diagnostics for cancer. However, the investigation of the roles of carbohydrates in fundamental biological processes and their potential as novel therapeutic agents has been limited by the low abundance of many glycan structures from natural sources.3 Cellular systems that overexpress glycoproteins have been found to generate heterogeneous glycan pools.13,14 Genetic research has tried to identify the genes responsible for glycosylation in specific types of cells. Glycomics is poised to become a dynamic research area as more robust laboratory techniques and targeted reagents become available.

This issue of BioFiles highlights Sigma’s key products for glycomics and glycoproteomics research techniques, including enzymatic glycan synthesis, glycoprotein deglycosylation strategies, and glycan detection methods. Glycolytic enzymes and lectins, proteins in which Sigma has historic and core capabilities, are included as fundamental reagents for carbohydrate studies.

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References

  1. For a collection of papers on glycoconjugates please see Carbohydr. Res., 164 (1987).
  2. Varki, A., Glycobiology, 3, 97 (1993).
  3. Dwek, R.A., Chem. Rev., 96, 683 (1996).
  4. Sears, P., and Wong, C.-H., Cell. Mol. Life Sci., 54, 223 (1998).
  5. Paulson, J.C., in The Receptors, P.M. Cohn (ed.), Academic Press, New York, Vol. 2, 131 (1985).
  6. Sairam, M.R., in The Receptors, P.M. Cohn (ed.), Academic Press, New York, Vol. 2, 307 (1985).
  7. Hakomori, S., Cancer Res., 45, 2405 (1985).
  8. Kren, V., et al., J. Chem. Soc. Perkin Trans. I, 2481 (1994).
  9. Riva, S., J. Molecular Catalysis B: Enzymatic, 43, 19 (2002).
  10. Ashwell, G., and Harford, J., Ann. Rev. Biochem., 51, 531 (1982).
  11. Berger, E.G., et al., FEBS Lett., 203, 64 (1986).
  12. Jacoby W.B. (ed.): Enzymatic Bases of Detoxification, Academic Press, New York, Vol. 2, (1980).
  13. Schachter, H., Biochem. Cell Biol., 64, 163 (1985).
  14. Jenkins, R.A., et al., Nat. Biotechnol., 14, 975 (1996).

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