סוכרים, לקטינים וגליקוביולוגיה (0452.3125) Glycans, Lectins and Glycobiology

GLYCOBIOLOGY Gerardo Lederkremer, Dan Peer and Vered Padler-Karavani. Dept. of Cell Research and Immunology. Structure, biosynthesis and functions of the carbohydrates of glycoproteins and glycolipids. Lectins. Medical relevance and biotechnological applications. THE COURSE IS GIVEN FOR MSC AND PHD STUDENTS AND OPEN FOR A LIMITED NUMBER OF 3RD YEAR BSC STUDENTS. Topics: •Monosaccharides: As constituents of the glycoconjugates, with emphasis on the sialic acids. •Glycoproteins: Isolation and characterization. Structure. Carbohydrate-peptide linkages, N-linked, O-linked. The glycosylphosphatidyl inositol (GPI) anchor. Impact of glycosylation on glycoprotein lifetime in circulation and on the activity of enzymes, hormones, immunoglobulins, cytokines and receptors. Uses in the pharmaceutical and the biotechnology industry. Biosynthesis; sugar nucleotides and lipid-linked intermediates; glycosyltransferases; biochemical pathways. Role of sugar chain processing in glycoprotein folding and quality control. Congenital diseases of protein glycosylation (CDGs). •Proteoglycans: Structure. Function as structural elements of connective tissues and of cell membranes. Proteoglycans as receptors for growth factors and in cancer biology. Heparin, an anticoagulant. The mucopolysaccharidoses – genetic defects of glycosaminoglycan degradation. •Lectins: Functions in animal cell biology, e.g. in leukocyte migration, in inflammatory diseases and in cancer. Role of lectins in microbial invasion and as tools in glycoconjugate research. Anti-adhesion therapy of infections, inflammations and cancer. •Glycolipids: Structure, function. Biosynthesis. Genetic defects in glycolipid catabolism. Lysosomal storage diseases: the I-cell disease, the mannose-6-phosphate marker and its receptor; Gaucher disease and enzyme replacement therapy. •Polysaccharides as building blocks in nano-therapeutics: Chemical structure of polysaccharides (Chitosan, Arabinogalactan, Cyclodextrin, Dextran, Alginate, and hyaluronan as examples). The main mechanisms of nanoparticle preparation from polysaccharides, basic introduction to nanotechnology and nanomedicine. Polysaccharide-based nanoparticles, use for diagnostics and therapeutics. •Cell surface carbohydrates in cell recognition and their variations during differentiation, development and in cancer and other diseases. ABO blood group determinants. Cell surface carbohydrates in immune recognition and as signaling molecules. Textbook: •Introduction to Glycobiology, 3rd edn. M.E. Taylor, K. Drickamer, Oxford University Press, 2011. References: • Essentials of Glycobiology. 2nd. Edition. Edited by Varki, A., Cummings, R.D., Esko, J.D., Freeze, H.H., Stanley, P., Bertozzi, C.R., Hart, G.W., and Etzler, M.E. CSHL Press, Cold Spring Harbor, N.Y., (2009). (http://www.ncbi.nlm.nih.gov/books/NBK1908/) • Nelson, D.L. and Cox, M.M., Lehninger- Principles in Biochemistry 5th Ed., Chapter 11, Carbohydrates and Glycobiology (2008). • Berg, J.M., Tymoczko, J.L. and Stryer, L. Biochemistry 5th Ed., Chapter 11, Carbohydrates (2002). • Lodish, H., Berk, A., Kaiser, C.A., Krieger, M., Scott, M.P., Bretscher, A., Ploegh, H. and Matsudaira, P. Molecular Cell Biology 6th Ed., Chapters 13 and 19, (2008). • Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K. and Walter, P., Molecular Biology of the Cell 5th Ed., Chapters 12 and 19, (2008). •”Carbohydrates in cell recognition”, N. Sharon and H. Lis, Scientific American 268 (1) 82-89 (1993); ”Sweet Medicines” T. Maeder, Scientific American 287(1) 40-47 (2002).

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מטלת סיום: בחינה בכתב

ספרות: Introduction to Glycobiology, 3rd edn. M.E. Taylor and K. Drickamer, Oxford University Press, 2011