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Glycobiology. The study of the structure, chemistry, biochemistry and biological function of complex carbohydrates. Classes of Biochemicals . Lipids, fats, isoprenoids, terpenes Structural, information, energy source
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Glycobiology The study of the structure, chemistry, biochemistry and biological function of complex carbohydrates. Downloaded from www.pharmacy123.blogfa.com
Classes of Biochemicals • Lipids, fats, isoprenoids, terpenes • Structural, information, energy source • Proteins (high information content by molecular recognition of structures in defined binding sites). • Structural, informational, catalytic (enzymes), energy source when converted to CHO or lipid • Nucleic acids • information, structural, enzymes)(energy-ATP) • Carbohydrates (CHO) • Structural, informational (no enzymes yet) • (nucleic acids are a subclass of polysaccharides) • Energy content Downloaded from www.pharmacy123.blogfa.com
Carbohydrates, sugars • Historical background, chemistry, biosynthesis • Saccharide structure and nomenclature review • Analytical Methods and Biotechnology Applications: • Evolution of Glycan diversity, information potential • Protein-glycan interactions, binding, recognition, • signaling, adhesion, immunology: • - Proteins that recognize glycans (immune and non-immune), molecular specificity • Biological roles of glycans, Bioactivity • Glycans in Genetic Disorders and Disease • Microbial Adhesion and Virulence • Opportunities for Biotechnology Development • Text: Essentials of Glycobiology, 1999, Eds. Varki and Cummings: ISBN 0-87969-560-9 Downloaded from www.pharmacy123.blogfa.com
Rudimentary structures • http://wngr343a.chem.orst.edu/~gablek/CH336/Chapter24/aldoses.htm • Simple monosaccharides • Trioses (3 carbons), 1 chiral center, 2 isomers • Tetroses (4 carbons), 2 chiral centers, 4 isomers • Pentoses (5 carbons, 3 chiral centers, 8 isomers • Hexoses (6 carbons, 4 chiral centers, 16 isomers • D-series sugars (highest chiral hydroxyl to the right in a Fischer projection. • L-series sugars (opposite) • Anomeric carbon (carbon 1 for aldoses, carbon 2 or other for ketoses Downloaded from www.pharmacy123.blogfa.com
Historical synthesis, analysis • Emil Fischer (late 19th, early 20th cent) • X-ray crystallography, 1940’s-50’s • D-sugars correctly guessed by Fischer • Crystallization of derivatives, melting points, rotation of plane polarized light • Thus “D” originally meant “dextrarotatory” and “L” meant “levorotatory”. Downloaded from www.pharmacy123.blogfa.com
Analytical Methods • Wet chemical methods, colorimetry, etc. • Enzymology • Spectroscopy • Optical rotation (historical) • Mass spectrometry • NMR • X-ray Downloaded from www.pharmacy123.blogfa.com
Diversity of structures, Information carrying potential • Laine, RA (1994) “A Calculation of all Possible Oligosaccharide Isomers, Both Branched and Linear Yields 1.05 x 1012 Structures for a Reducing Hexasaccharide: The Isomer Barrier to Development of Single-Method Saccharide Sequencing or Synthesis Systems” • Glycobiology 4:759-767. Downloaded from www.pharmacy123.blogfa.com
InformationBiological roles of glycans, Bioactivity • Protein-glycan interactions, binding, recognition • Antibodies (ABO blood groups, etc.) • Lectins (special class of sugar-binding proteins) • Enzymes • Signalling, blood clotting (heparin) • Receptors (signals, microbial attachment) • Carbohydrate-carbohydrate binding • controversial Downloaded from www.pharmacy123.blogfa.com
Glycans in Genetic Disorders and Disease • Transplantation antigens other than MHC’s • Blood transfusion studies of carbohydrates! • Diseases due to errors of metabolism • Mutated enzymes of biodegradation: • Mostly lysosomal storage diseases • Tay-sachs, Fabry’s, Hunters, Gauche’s • Mutated enzymes of biosynthesis: • HEMPAS, other blood disorders • Knock-out mouse studies of function Downloaded from www.pharmacy123.blogfa.com
Microbial Adhesion and Virulence • Bacterial colonization receptors • Alpha-galactose e. coli receptor • Helicobacter pylorus • Cholera receptor • others • Virus receptors • Influenza (sialic acid) • Herpes (heparinoids) • Bacteriophage • others Downloaded from www.pharmacy123.blogfa.com
Opportunities for Biotechnology Development-pharmaceuticals • Blood clotting control • Cancer (group B streptococci) • Antivirals (receptor inhibitors, rotavirus) • Cell growth controllers (heparinoids, others) • Anti-inflammatories (selectin inhibitors) • others Downloaded from www.pharmacy123.blogfa.com
Opportunities for Biotechnology Development-Diagnostics • Bacterial diagnostics (recognition of cell surface carbohydrates) • Today - blood types, vaccines • Viral diagnostics (receptor-based) • Fungal diagnostics • http://www.lsu.edu/highlights/033/sin.html Downloaded from www.pharmacy123.blogfa.com
glycobiology Student presentations: Powerpoint Preview of talk Present a paper with data Downloaded from www.pharmacy123.blogfa.com