Glycomics

The carbohydrate-containing molecules of protozoan parasites have been studied for some 40 or so years, and the results of the many studies indicate that these glycoconjugates display a high degree of species specificity. Nevertheless, a number of major c

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Glycomics Iain B.H. Wilson

Abstract

The carbohydrate-containing molecules of protozoan parasites have been studied for some 40 or so years, and the results of the many studies indicate that these glycoconjugates display a high degree of species specificity. Nevertheless, a number of major classes of glycoconjugate can be distinguished – whether the glycans be N, O or P linked to protein or are lipid linked. Although modern glycomic analyses have enabled advances in our knowledge, many questions remain regarding structure, biosynthesis and function. In many cases, roles in virulence can be proposed, and the potential for glycans to be important for diagnosis or therapy is significant.

3.1

Introductory Comments

The surfaces of all cells display a range of glycoconjugates, ranging from simple glycolipids, glycoproteins with N- and O-linked oligosaccharides and/or glycolipid anchors through highly heterogeneous polysaccharides (Varki 2011). Protozoan parasites are no exception; indeed, these organisms express a wide range of carbohydrates, many of which are unique to certain species or show divergence from those from more familiar organisms (Guha-Niyogi et al. 2001). Furthermore, interactions of parasites with hosts and vectors are dependent on glycans with either the parasite expressing a glycoconjugate recognised by the host or vector or vice versa. By comparison to bacterial pathogens and metazoan parasites, it is not unlikely that protozoan glycoconjugates are involved in immunoregulation or are potential

I.B.H. Wilson Department of Chemistry, University of Natural Resources and Life Sciences (BOKU), Muthgasse 18, A-1190 Vienna, Austria e-mail: [email protected] © Springer-Verlag Wien 2016 J. Walochnik, M. Duchêne (eds.), Molecular Parasitology, DOI 10.1007/978-3-7091-1416-2_3

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vaccine candidates; however, the ‘non-template-driven’ nature of glycan biosynthesis and the branched nature of many oligosaccharides mean that they are challenging molecules to study in terms of their molecular structure and biological function.

3.2

Major Glycomic Techniques

The fact that a typical monosaccharide can be attached through any of four free hydroxyl groups to another monosaccharide means that glycan structures have an inherent structural complexity quite unlike that of proteins and nucleic acids; this means that glycan analysis is much more than the ‘reading off’ of series of constituent components of a linear polymer; not only is the ‘connectivity’ (which type of monosaccharide or other modifications is next in the row) to be considered but also the position of the modification around the sugar ring, the potential branching of the glycopolymer and the chirality of the linkages. This means a strategy analogous to Sanger or Edman sequencing as for DNA or peptides is not appropriate. Furthermore, a glycan is generally part of a glycoconjugate; very often the glycan part is analysed in isolation and thus must be released from the underlying lipid or protein by enzymatic or chemical means. Over