on glycan synthesis, and the creativity of the entire synthesis community needs to be leveraged to solve the long-standing and vexing problems of stereoselective, regioselective syntheses with simple, high-yielding reactions. The biochemistry and genetics communities need to participate in identifying all enzymes and characterizing all pathways involved in glycan metabolism. Finally, computer scientists, modelers, and bioinformaticists need to be fully engaged. The community needs to set up glycoscience databases and integrate glycoscience into existing biological databases. Glycan and proteoglycan structure prediction and modeling tools need to be developed. Full interaction pathways must be developed to incorporate all aspects of glycobiology into systems biology. Details of these opportunities are described in the remainder of this chapter, but the main message is clear: Glycoscience needs the full participation of the broader scientific community to help develop tools that can solve some of the most vexing problems in glycoscience and to catalyze its integration into the scientific mainstream. By helping develop tools for glycoscience, it is expected that these tools will have follow-on benefits to all fields of science.

5.1     SYNTHESIS

5.1.1 General Aspects

The development of routine procedures for automated chemical synthesis of oligonucleotide fragments (DNA and RNA) and peptides has brought significant change to modern biology. Unfortunately, no general methods are available for the preparation of complex carbohydrates (Boltje et al. 2009; Kiessling and Splain 2010). As a result, the synthesis of a target is often a research project unto itself, which may take many months and in some cases years to complete. This problem is compounded by the fact that glycoconjugates in biological samples are often found in low concentrations and in microheterogeneous forms, greatly complicating their isolation and characterization. Glycomes of eukaryotic organisms are extremely diverse; for example, it has been estimated that the human glycome contains 10,000 to 20,000 minimal epitopes for glycan-binding proteins (Cummings 2009). Thus, robust synthetic technologies are urgently needed that can readily provide large collections of complex oligosaccharides. Furthermore, biological and analytical studies often require glycans to be modified by a tag, immobilized to surfaces, presented at a multivalent scaffold, or attached to a lipid, peptide, or protein (Seeberger and Werz 2007; Rich and Withers 2009). As a result, additional technologies are required that can readily provide such conjugates.

Current approaches for obtaining well-defined oligosaccharides and



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