Novel ionic-based tools for glycoscience

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Cell surface carbohydrates offer tremendous unexploited potential as molecular fingerprints that can distinguish disease cells from normal cells. However, cell-surface glycans are extraordinarily challenging molecules to characterize, requiring major investments in highly specialized technology and expertise and that is precisely why their full potential has not yet been realized. Developing the tools that will make the study of cell surface carbohydrates possible, offers the possibility of developing early diagnostic tests, as well as new therapeutic targets and vaccines. Despite the importance of these complex molecules, the synthesis of structurally defined complex carbohydrates is still a very laborious process that requires a high level of technical expertise. This lack of rapid, high throughput synthetic methodologies to provide pure products has hampered progress in glycobiology research, which has had to rely on either isolated materials or traditional, lengthy, target-oriented oligosaccharide synthesis. This is a multidisciplinary project involving synthetic organic chemists, glycobiologists, enzymologists and molecular biologists. The proposal centers on the chemical and enzymatic synthesis of novel O-glycan tools following the methodology recently developed within our team, whereby a versatile ionic tag based "catch-and-release" strategy that requires no chromatography after each reaction step, and that is compatible with chemical and enzymatic oligosaccharide synthetic protocols will be employed. The novel oligosaccharide probes will be used for the study of the O-glycosylation patterns of gastrointestinal and ocular mucins that are relevant to disease. We are addressing a timely problem - lack of O-glycan probes for study - while developing the synthetic tools to make oligosaccharide synthesis available to main stream chemists.