BIO-ORGANIC CHEMISTRY AND
Learning outcomes of the course unit
Aim of the part of course relative to Bioorganic Chemistry is the study of the main biological pathways that produce secondary metabolites. Their metabolic, physiological and pharmaceutical role will be discussed either in the producing organisms or in the receiving organisms
Aim of the part of the course relative to Glycomic is 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
Energy, work, order; energy preservation and thermodynamic laws; energy fluxes in nature and in systems far from equilibrium. Evolution in biological systems; Prebiotic chemistry, biological homochirality, prokariotes and eukariotes, Catabolism, harvesting the light. Enzymes and coenzymes; role of enzymes and coenzymes in biological catalysis; vitamines.
Terpenes; biogenesis of terpenes, monoterpenes, sesquiterpenes, diterpenes, natural rubber; squalene e phitoene, carotenoids, cicle of vision.
Steroids; biogenesis of steroids, squalene, lanosterol, cholesterol; corticosteroids, sexual hormones, bile salts; physiological role.
Fatty acids; biogenesis of saturated, monounsaturated, poliunsaturated fatty acis; Biogenesis of prostaglandines, tromboxanes, leukotrienes, lipoxines; physiological role.
Acetogenines; biogenesis of acetogenines, flavanoids.
Antibiotics; biogenesis and physiological role of the antibiotics; mechanisms of action of antibiotics.
Shikimic acid; biogenesis of the shikimic acid; aromatic ammino acids, tetracyclines.
Alcaloids; nomenclature, classification and biological role; biogenesis of selected compounds.
The sugar code: carbohydrates and glycoconjugates as source of biological information in the development and life of cells. Examples of involvement of carbohydrates in physiological and patological events.
Structure, nomenclature, chemico-physical properties and reactivity of carbohydrates. Formation of the glycosidic bond. Oligo and polysaccharides. Concept of glycosil donor and acceptor. Chemical activation of the anomeric position. Chemical modification of monosaccharides and chemical synthesis of oligosaccharides, glycoconjugates and neoglycoconjugates.
Monosaccharide biosynthesis and interconversion in primary and secondary metabolism.
Polysaccharide degradation. Depolymerizing enzymes: glycosidases, transglycosidases, phosphorilases, lyasis. Depolimerization mechanisms. Interaction nature between glycosidic substrates and enzymes.
Use of glycosidases in synthesis of glycosidic bond. Thermodynamic and cinetic approaches. Regio - and stereoselectivity. Non-natural substrates.
Effects of mutation in glycosidase and use of engineered glycosidases (glycosynthases) with non-natural substrates.
Biosynthesis and interconversion of glycosylnucleotides.
Biosynthesis of glycosidic bond: glycosyltransferases. Repetitive and non-repetitive glycosyltransferases, dolicoldiphosphate-dependent and glycosylnucletide dependent glycosyltransferases. Regio- and stereoselectivity.
Use of glycosyltransferases and tandem use with other enzymes for chemoenzymatic synthesis of oligosaccharides, glycoconjugates and mimics. From in vitro to in vivo synthesis of saccharides.
Post-synthetic modification of saccharides. Sulfotransferases in action.
Protein receptors for carbohydrates: the lectins. Interactions between non-enzymatic receptors and saccharide substrates. The concept of multivalency and glycoside cluster effect. Synthetic non -natural multivalent ligands for lectin inhibition. Glycoside based vaccines.
Technics for strucutral identification and study of recognition phenomena involving carbohydrates.
P. M. Dewick, Chemistry, biosyntesis and bioactivity of organic natural substances, Piccin, Padova
The Sugar Code. Fundamentals of Glycosciences, Hans-Joachim Gabius Ed., 2009 Wiley -VCH Verlag, Weinheim
Carbohydrates in Chemistry and Biology, B. Ernst, G. W. Hart, P. Sinay Eds., Vol. 1-4, 2000 Wiley -VCH Verlag, Weinheim
Molecular and Cellular Glycobiology, M. Fukuda, O. Hindsgaul Eds., 2000 Oxford Universityy Press
Introduction to Glycobiology, M. E. Taylor, K. Drickamer Eds., 2006 Oxford University Press
Bioorganic Chemistry - Carbohydrates, S. M. Hecht Ed., 1999 Oxford University Press
The Molecular and Supramolecular hemistry of Carbohydrates, S. David Ed., 1997 Oxford University Press
Frontal lectures and oral examination