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 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 Structural, information, energy source 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 Downloaded from and Cummings: ISBNwww.pharmacy123.blogfa.com 0-87969-560-9 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 SingleMethod Saccharide Sequencing or Synthesis Systems” Glycobiology 4:759-767. Downloaded from www.pharmacy123.blogfa.com Information Biological 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