Glycobiology

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Glycobiology

• The study of the structure, chemistry,
  biochemistry and biological function of complex
  carbohydrates.

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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

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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

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Rudimentary structures

• http//wngr343a.chem.orst.edu/gablek/CH336/Chapte
  r24/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

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Historical synthesis, analysis

• Emil Fischer (late 19th, early 20th cent)
• X-ray crystallography, 1940s-50s
• 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.

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Analytical Methods

• Wet chemical methods, colorimetry, etc.
• Enzymology
• Spectroscopy
• Optical rotation (historical)
• Mass spectrometry
• NMR
• X-ray

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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 4759-767.

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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

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Glycans in Genetic Disorders and Disease

• Transplantation antigens other than MHCs
• Blood transfusion studies of carbohydrates!
• Diseases due to errors of metabolism
• Mutated enzymes of biodegradation
• Mostly lysosomal storage diseases
• Tay-sachs, Fabrys, Hunters, Gauches
• Mutated enzymes of biosynthesis
• HEMPAS, other blood disorders
• Knock-out mouse studies of function

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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

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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

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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

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glycobiology

• Student presentations
• Powerpoint
• Preview of talk
• Present a paper with data