BIOORGANIC CHEMISTRY OF CARBOHYDRATES I
Learning outcomes of the course unit
To give insights:
- on carbohydrate reactivity, in particular on the formation of the glycosidic bond to generate oligo- and polysaccharides by chemical, chemoenzymatic and biochemical methods;
- on bioorganic processes relative to metabolism and biochemistry of simple and complex carbohydrates, their degradation, interconversion and use to produce oligo-, polysaccharides and glycoconjugates.
- 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 contents summary
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.
Primary metabolism of monosaccharides. Glycolysis, oxidative pentose phosphate pathway, interconversion between monosaccharides.
Saccarose degradation. Saccarose synthase. Secondary Metabolism. Biosynthesis and interconversion of nucleoside-(di)phospho-monosaccharides.
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.
Phosphorylases in the synthesis of oligosaccharides.
Biosynthesis of glycosidic bond: glycosyltransferases in action. Ripetitive and non-ripetitive glycosyltransferases, polyprenoldiphosphate-dependent and nucleoside diphospho-monosaccharide-dependent glycosyltransferases. Regio- and stereoselectivity.
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.
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.
Post-synthetic modification of oligo- and polisaccharides. Sulfotransferases in action.
Techniques for the structural identification of carbohydrates and for studying interaction phenomena involving carbohydrates.
Maureen E. Taylor, Kurt Drickamer in Introduction to Glycobiology, Oxford University Press, Second Edition, 2003
Molecular and Cellular Glycobiology, Eds. M. Fukuda and O. Hindsgaul, Oxford University Press, 2000
Bioorganic Chemistry - Carbohydrates, Ed. S. M. Hecht, Oxford University Press, 1999
Carbohydrates in Chemistry and Biology, Eds. B. Ernst, G. W. Hart, P. Sinay, Wiley-VCH, 2000
Microbial Degradation of Natural Products, Ed. G. Winkelmann, VCH, 1992
Glycoscience: Chemistry and Chemical Biology, Eds. B. Fraser-Reid, K. Tatsuta, J. Thiem, Springer Edition, 2001
Research articles on the different topics