1CarbohydratesBCMB 8020April 7, 2009Dr. Lianchun WangEmail: [email protected]’s lecture…- goals of the course- review of the syllabus and general lecture format- recommended and required reading material- chemical background of sugars and polysaccharides- oligosaccharide diversity- key concepts in oligosaccharide biosynthesis3Goals of the course:- understand the biochemistry of sugars and oligosaccharides- learn the approaches used to analyze carbohydrate content and structure - appreciate the structural diversity of oligosaccharides in different biological systems- understand the function of oligosaccharides in different organisms- appreciate the current research frontiers in areas of glycobiology and the biomedical relevance of oligosaccharides4General lecture format:glycan type/biological system: 1) structure2) biosynthesis3) function4) research frontiersRequired and recommended reading materialVoet and Voet (3rd edition) - Chapter 8“Essentials of Glycobiology” (2nd Edition) - Chapters 2, 8, 9,15,16, 20, 21, 39, 47 (available online at PubMed under “Books”)Review and journal articles5The Chemistry and Biochemistry of Sugars6Carbohydrate = saccharide = “sugar”• most abundant biological molecule• Chemical simple: C, H, O - (CH2O)n• Basic unit: monosaccharide• Monosaccharide covalently link togetherto form polysaccharide• Structurally more heterogenous than protein andnucleic acids: size & composition• Biological functions: Multiple - energy source,structural materials, mediate many key recognitionevents between proteins and cells.(CH2O)67Monosaccharides are aldoses or ketosesaldoseketoseFischer projections8Monosaccharides are aldoses or ketosesaldoses9ketoses10C=OHH - C - OHHO - C - HCH2OHHO - C - HHO - C - HL-GlucoseAccording to the Fischer convention, D-sugars are the mirror images of L-sugarsD-sugar vs. L-sugar11all D-sugars have the same absolute configuration at the asymmetric center farthest removed from their carbonyl group12Epimers The sugars that differ only by the configuration around one C-atomD-glucose and D-mannose are epimers13Cyclic sugars Hydroxyl groups and either the aldehyde or ketone groups of monosaccharides can react intramolecularly to form cyclic sugars14Haworth projections are convenient formulas to represent the configurationof sugar substituents15Sugars with a 6- and 5-membered ring are known as pyranoseand furanose, respectively- internal strain of 3 and 4-membered rings makes them less stable than the linear strains16Cyclic sugars have two anomeric forms (! and ß)- the cyclization of a monosaccharide renders the carbonyl carbon asymmetric- in solution, D-glucose is a mixture of the ß anomer (63.6%) and the ! anomer (36.4%), (linear form is present in very small amounts)- the pure anomers have unique chemical properties (i.e. optical rotation)17Sugars can adopt different conformations- overall conformation of sugars is not planar: carbon centers have an sp3 hybridization- substituents can be either axial or equatorial; ß-D-glucose is the only sugar that can have all 5 of its non-H substituents in the equatorial position- the equatorial position of OH or CH2OH substituents is more sterically favored 18Conformation: (e.g. chair or boat) shifts readily since no bonds are brokenConfiguration: (e.g. ! and ß anomers) shift between anomers is slow in solution since bonds are broken and re-formedEpimerization: (e.g. C2 epimers, glucose vs. mannose) does not occur without appropriate enzyme19Sugars are often modified• Oxidation: 1). aldehyde gloup " carboxylic acid group = aldonic acide.g. gluconic acid 2). primary alcohol group " carboxylic acid group = uronic acide.g. glucuronic acid• Reduction: carbonyl group " polyhydroxy acohols = alditole.g. glycerol• Deoxygenation of hydroxyl group: Replace hydroxyl group by H.e.g. #-D-2-deoxyribose (DNA)• Amino sugars: Replace hydroxyl group by amino group.e.g. D-glucosamine, D-galactosamine• Methylation of hydroxyl group: occurs in nature, and also an approachfor structural analysis• Esterification of hydroxyl group: phosphate-, sulfate-20Glycosidic bonds- the bond that links two monosaccharides (technically, it is the bond connecting the anomeric carbon to the other molecules)Canomeric - OR’ = glycosidic bond21There are basically 2 things we need to keep track of: 1) the anomeric configuration of the “glycosidic linkage” 2) the identity of the carbon on the next sugar that shares thebridging oxygen22- naming begins with the sugar farthest from the “reducing terminus” of the oligosaccharide- the “reducing sugar” is the sugar that still contains a free anomeric carbonO-#-D-galactopyranosyl-(1"4)-D-Glucopyranose23Examples of glycosidic bonds24N-glycosidic bonds link the anomeric carbon and an amine, occurring the link between the sugars and bases of DNA and RNA25How are glycosidic linkages and oligosaccharides represented?- symbols are used to represent sugars instead of Haworth projections or chair diagrams26!4!4 ! 4 !29Ac "3"3 "6 ! 4 !2" 6 3""69Ac!4-!4 !4!29Ac "3 !4!2 "3"3"6"6"3SymbolicRepresentation Fuc" 3 Sia"3Gal!4GlcNAc!2Man" Fuc" 6 6 Man!4GlcNAc!4GlcNAc# 39Ac-Sia"6Gal!4GlcNAc!2Man"SimplifiedTraditionalGlycosidic bonds are shortened to convey only the position of the anomeric carbon and the carbon of the next sugar in the structureGlucoseß1,4 Galactose = Glcß4Gal27Chapter 1, Figure 6Common classes of animal glycans Essentials of GlycobiologySecond Edition28The diversity of oligosaccharides is enormous and gives these structures the capacity to mediate many important biological functions- the diversity of oligosaccharide structures stems from properties inherent to sugars themselves:* multiple monosaccharides* several configurations* many derivatives* multiple possible linkages* branching29The Complexity of CarbohydratesThe Complexity of Carbohydrates C H O C H O C Cnn(H(H22O)O)nn C C66(H(H22O)O)66 C C66HH1212OO66!!-D-Glucose (-D-Glucose (GlcGlc))##-D-Glucose (-D-Glucose (GlcGlc))OOHHHHOHOHH OHHOHHH112233445566OHHHHOHOHH OHOHOHHH11223344556630OHHHHOHOHH