Transcript Glycobiology

Glycobiology
The study of the structure,
chemistry, biochemistry and
biological function of complex
carbohydrates.
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Classes of Biochemicals
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Lipids, fats, isoprenoids, terpenes
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Proteins (high information content by
molecular recognition of structures in defined
binding sites).
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Structural, informational, catalytic (enzymes),
energy source when converted to CHO or lipid
Nucleic acids
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Structural, information, energy source
information, structural, enzymes)(energy-ATP)
Carbohydrates (CHO)
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Structural, informational (no enzymes yet)
(nucleic acids are a subclass of polysaccharides)
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Carbohydrates, sugars
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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,
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signaling, adhesion, immunology:
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- 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
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0-87969-560-9
Rudimentary structures
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http://wngr343a.chem.orst.edu/~gablek/CH336/Chapter24/aldoses.htm
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Simple monosaccharides
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Trioses (3 carbons), 1 chiral center, 2 isomers
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Tetroses (4 carbons), 2 chiral centers, 4 isomers
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Pentoses (5 carbons, 3 chiral centers, 8 isomers
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Hexoses (6 carbons, 4 chiral centers, 16 isomers
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D-series sugars (highest chiral hydroxyl to the right in a Fischer projection.
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L-series sugars (opposite)
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Anomeric carbon (carbon 1 for aldoses, carbon 2 or other for ketoses
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Historical synthesis, analysis
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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
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Thus “D” originally meant “dextrarotatory”
and “L” meant “levorotatory”.
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Analytical Methods
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Wet chemical methods, colorimetry, etc.
Enzymology
Spectroscopy
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Optical rotation (historical)
Mass spectrometry
NMR
X-ray
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Diversity of structures,
Information carrying potential
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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.
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Information
Biological roles of glycans, Bioactivity
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Protein-glycan interactions, binding,
recognition
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Antibodies (ABO blood groups, etc.)
Lectins (special class of sugar-binding proteins)
Enzymes
Signalling, blood clotting (heparin)
Receptors (signals, microbial attachment)
Carbohydrate-carbohydrate binding
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controversial
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Glycans in Genetic Disorders and
Disease
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Transplantation antigens other than MHC’s
Blood transfusion studies of carbohydrates!
Diseases due to errors of metabolism
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Mutated enzymes of biodegradation:
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Mostly lysosomal storage diseases
Tay-sachs, Fabry’s, Hunters, Gauche’s
Mutated enzymes of biosynthesis:
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HEMPAS, other blood disorders
Knock-out mouse studies of function
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Microbial Adhesion and
Virulence
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Bacterial colonization receptors
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Alpha-galactose e. coli receptor
Helicobacter pylorus
Cholera receptor
others
Virus receptors
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Influenza (sialic acid)
Herpes (heparinoids)
Bacteriophage
others
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Opportunities for Biotechnology
Development-pharmaceuticals
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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
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Bacterial diagnostics (recognition of cell
surface carbohydrates)
Today - blood types, vaccines
Viral diagnostics (receptor-based)
Fungal diagnostics
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http://www.lsu.edu/highlights/033/sin.html
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glycobiology
Student presentations:
Powerpoint
Preview of talk
Present a paper with data
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