Carbohydrate Structure and the Glycosidic Bond
Lance Wells
8130. Glycobiology, Spring 2005—Clinical Correlation PresentationsSession DatePresenters CC
Instructors Topic
Wells 1/20 Wells GalactosemiaCaryn Hale ([email protected])Lori Hill ([email protected])
1/27 Tiemeyer Storage diseases
Heather Strachan ([email protected])Olga Stuchlik ([email protected])
2/3 Tiemeyer CDG Syndromes
Monique Phillips ([email protected])Dan Sherling ([email protected])
2/10 Wells Muscular Dystrophy and O-linked structures that bind laminin
Melani Atmodjo ([email protected]) 2/15 Tiemeyer Selectins, lessons from glycan-based pharmaceuticaldevelopment
Sarah Bass ([email protected])Jidnyasa Gaekwad ([email protected])
2/24 Wells Antithrombin/heparin—structure activity relationships
Xiaogang Gu ([email protected]) 3/3 Wells Cystic fibrosis, quality controlAsong Jinkeng ([email protected])David Mokry ([email protected])
3/10 Wells Diabetes
Byoungjae Kim ([email protected]) 3/24 Tiemeyer Mgat1, requirement for complex/hybrid glycans, early arrestJoseph Moore ([email protected])Christine Oshansky ([email protected])
3/31 Tiemeyer Exostoses, growth factor modulation
Narendra Tejwani ([email protected])Xiang Yong ([email protected])
4/14 Tiemeyer NOD factors
Lu Meng ([email protected]) 4/21 Wells Tumor metastasis
WEBSITE: http://cell.ccrc.uga.edu/~glycobiology/
Carbohydrates - Definition and Language
Carbohydrates = “Hydrates” of carbon.
Hexose, e.g.: C6H12O6 = C(H2O)6.
Need to develop a system for talking about and/or representing carbohydrates.
Monosaccharides: single sugars; clear language and numerous pictorial forms.
Oligosaccharides (typically 4-10 sugars): need a more complex language, onlyone of previous pictorial forms remains tractable.
Polysaccharides: systematic language is accurate but cumbersome, newpictorial representation more useful.
Carbonyl containing compounds: Aldehydes RCHO and Ketones RCOR’
Glyceraldehyde and “Fischer Projections”
Glyceraldehyde (aldotriose), a 3 carbon aldehyde sugar or “aldotriose,” existsas 2 mirror image isomers.
d-glyceraldehyde l-glyceraldehyde
The origin of D vs. L nomenclature for sugars - does stereocenter farthest fromthe aldehyde terminus have the configuration of D- or L-glyceraldehyde?
Dihydroxyacetone (ketotriose): No chiral carbon.
All monosaccharides with one exception have at least one chiral carbon withthe total number (k) being equal to the number of internal (CHOH) groups;
that is n-2 for Aldoses and n-3 for Ketoses with n=number of carbonatoms in the monosaccharide.
Possible Stereoisomers = 2 raised to the power of k (how many for hexose?)
CH2OH
CH2OHO
D-”Alditols” with 4 Carbons
Two possible isomers at each new carbon center.Mentally insert new carbon center between aldehyde terminus (C1) and what
was previously C2.Note that D configuration is retained.Two sugars that differ only in the configuration around a single chiral carbon
are called EPIMERS
D-”Alditols” with 5 Carbons
Xyl Rib**
Which 5 carbon sugars are epimers of D-ribose?
6 carbon ketose: fructose fru
D-”Alditols” with 6 Carbons
** special attention to Gal, Man, and Glc abbreviations
Gal Man Glc
Fischer Structures Does Not Take Into Account that5 and 6 Carbon Sugars Tend to Cyclize:
RING CONFIRMATION
Cyclization Can Produce Multiple Isomers
Fischer Projection is NOT good enough
From Fischer to Haworth to abbreviated Haworth diagrams.
Looking down the carbon spine from C1 down of the Fischer projection, notingwhether hydroxyl groups are to the right (down) or left (up). Now imaginearound the periphery of a flat hexagon.
“A new asymetric carbon” is formed so we need more language (great!)New asymetric carbon is termed the anomeric carbon and α is used to denote the
anomer where the absolute stereochemistry of the anomeric position and themost remote sterocenter in the sugar chain are the same, β opposite
For Hexoses Alpha=anti (anomeric hydroxyl to C6); Beta=beside
Where did this pyranose (p) term come from?
Pyranose (p) and Furanose (f)both 5 and 6 membered rings are stable so:
What about ketoses
Repeating the exercise for a 6 carbon ketose:
A Last Bit of Nomenclature for Chair Structures (the mostaccurate way of drawing the sugars) Haworth suggests that
sugars are flat but neither furanose or pyranose rings areactually flat in their lowest energy confirmations
Although D-glucose has a strong preference for one chair conformation, this isnot true for all sugars.
A Few of the Common non-(CH20)n BuildingBlocks of Oligosaccharides
Products of esterification, oxidation, reduction, acetylation, etc.
GlcA
lactones
acetyl
deoxy
sialyic acids
MutatrotationIn solution anomers can introconvert
% Distribution at 20CPyranose Furanose
α β α βD-Glc 34 65 0.5 0.5D-Gal 32 64 1 3D-Man 66 34 0 0D-Fru 4 68 1 30
The Glycosidic Bond
How do we describe molecules containing sugars that are attached to oneanother? (We’ll limit our discussion to cases where the anomeric center ofone sugar is attached to an oxygen atom of another sugar - that is, we’lldiscus only “glycosides.”)
There are basically 2 things we need to keep track of: 1) the anomericconfiguration of the “glycosidic linkage,” and 2) the identity of the carbonon the next sugar that shares the bridging oxygen.
Naming of Oligosaccharides
Here’s a simple example: maltose, or D-Glc-α(1-4)-D-Glc.
How did we come up with that name, how do we know which sugar to name 1st?We always begin naming with the sugar furthest from the “reducingterminus” of the oligosaccharide. The “reducing sugar” is the sugar that stillcontains a free anomeric carbon. Branches are put in parenthesis. Notice theα or β is now no longer “free” but is fixed in one orientation.
Many “common name” disacharrides (sucrose, lactose, etc.)-see Ess. Glycobiol.Note: we even keep this nomenclature when the oligosaccharide is attached to an
aglycone
O
O O
HO
HO
HO
HOHO
HO
HOOH
maltose
D-Glc-α(1-4)-D-Glc
Example of Naming a Branched Oligosaccharide
Final PointPictorial system is becoming “the standard” representation (especially for
complex structures)
β4β4
β 4 β2
9Ac
α3α3
α6 β 4 β2
α 6 3α
α69Acβ4 -
β4 β4 β2
9Ac
α3
β4 β2 α3
α3α6α6
α3
SymbolicRepresentati
on
Fucα 3 Siaα3Galβ4GlcNAcβ2Manα Fucα 6 6 Manβ4GlcNAcβ4GlcNAc∼ 39Ac-Siaα6Galβ4GlcNAcβ2Manα
SimplifiedTraditional