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.
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.
Bibliography
<br />Maureen E. Taylor, Kurt Drickamer in Introduction to Glycobiology, Oxford University Press, Second Edition, 2003<br />Molecular and Cellular Glycobiology, Eds. M. Fukuda and O. Hindsgaul, Oxford University Press, 2000<br />Bioorganic Chemistry - Carbohydrates, Ed. S. M. Hecht, Oxford University Press, 1999<br />Carbohydrates in Chemistry and Biology, Eds. B. Ernst, G. W. Hart, P. Sinay, Wiley-VCH, 2000<br />Microbial Degradation of Natural Products, Ed. G. Winkelmann, VCH, 1992<br />Glycoscience: Chemistry and Chemical Biology, Eds. B. Fraser-Reid, K. Tatsuta, J. Thiem, Springer Edition, 2001<br />Research articles on the different topics
