Learning objectives
<br />To give insights: <br />- on carbohydrate reactivity, in particular on the formation of the glycosidic bond to generate oligo- and polysaccharides by chemical, chemoenzymatic and biochemical methods; <br />- on bioorganic processes relative to metabolism and biochemistry of simple and complex carbohydrates, their degradation, interconversion and use to produce oligo-, polysaccharides and glycoconjugates.<br />- on the role played by carbohydrates and glycoconjugates in intercellular and intermolecular interaction phenomena and the possibility to interfer with them with synthetic molecular systems.
Prerequisites
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Course unit content
<br />Structure, nomenclature, chemico-physical properties and reactivity of simple saccharides. Glycosidic bond synthesis. Oligo - and polysaccharides. Glycosyl donor, glycosyl acceptor and protecting groups. Activation of the anomeric position. Chemical modification of monosaccharides and chemical synthesis of oligosaccharides.<br />Primary metabolism of monosaccharides. Glycolysis, oxidative pentose phosphate pathway, interconversion between monosaccharides.<br />Saccarose degradation. Saccarose synthase. Secondary Metabolism. Biosynthesis and interconversion of nucleoside-(di)phospho-monosaccharides.<br />Polysaccharides degradation. Depolymerising enzymes: glycosidases, transglycosidases, phosphorylases, lyases. Depolymerisation mechanisms. Interactions between saccharide substrates and enzymatic site. Effect of mutations in glycosidases. Glycosidases and engineered glycosidases (glycosynthases) in the synthesis of glycosidic bond. Thermodynamic and cinetic approach. Regio- and stereoselectivity. Non-natural substrates.<br />Phosphorylases in the synthesis of oligosaccharides.<br />Biosynthesis of glycosidic bond: glycosyltransferases in action. Ripetitive and non-ripetitive glycosyltransferases, polyprenoldiphosphate-dependent and nucleoside diphospho-monosaccharide-dependent glycosyltransferases. Regio- and stereoselectivity.<br />Carbohydrates as information source in the intercellular and intermolecular interactions: oligo-, polysaccharides and glycoconjugates in biologically relevant events. Carbohydrate binding proteins without enzymatic activity: the lectins. Interactions between receptor and saccharide substrate. The concept of multivalency and glycoside cluster effect. Synthetic multivalent ligands for lectin inhibition. Glycoside based vaccines.<br />Use of glycosyltransferases and their combination with other enzymes for the chemoenzymatic synthesis of oligosaccharides, glycoconjugates and glycoside mimics. From the in vitro to the in vivo synthesis.<br />Post-synthetic modification of oligo- and polisaccharides. Sulfotransferases in action.<br />Techniques for the structural identification of carbohydrates and for studying interaction phenomena involving carbohydrates.
Full programme
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Bibliography
The Sugar Code. Fundamentals of Glycosciences, Hans-Joachim Gabius Ed., 2009 Wiley -VCH Verlag, Weinheim<br />
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Carbohydrates in Chemistry and Biology, B. Ernst, G. W. Hart, P. Sinay Eds., Vol. 1-4, 2000 Wiley -VCH Verlag, Weinheim<br />
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Molecular and Cellular Glycobiology, M. Fukuda, O. Hindsgaul Eds., 2000 Oxford Universityy Press<br />
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Introduction to Glycobiology, M. E. Taylor, K. Drickamer Eds., 2006 Oxford University Press<br />
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Bioorganic Chemistry - Carbohydrates, S. M. Hecht Ed., 1999 Oxford University Press<br />
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The Molecular and Supramolecular Chemistry of Carbohydrates, S. David Ed., 1997 Oxford University Press
Teaching methods
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Assessment methods and criteria
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Other information
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