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 (crhale@uga.edu)Lori Hill (lorihill@uga.edu)

1/27 Tiemeyer Storage diseases

Heather Strachan (strachan@bmb.uga.edu)Olga Stuchlik (ostuchl@uga.edu)

2/3 Tiemeyer CDG Syndromes

Monique Phillips (4nique@uga.edu)Dan Sherling (dan@uga.edu)

2/10 Wells Muscular Dystrophy and O-linked structures that bind laminin

Melani Atmodjo (mel2003@uga.edu) 2/15 Tiemeyer Selectins, lessons from glycan-based pharmaceuticaldevelopment

Sarah Bass (sbaas@uga.edu)Jidnyasa Gaekwad (jgaekwad@uga.edu)

2/24 Wells Antithrombin/heparin—structure activity relationships

Xiaogang Gu (xggu@uga.edu) 3/3 Wells Cystic fibrosis, quality controlAsong Jinkeng (jinkeng@uga.edu)David Mokry (dzmokry@uga.edu)

3/10 Wells Diabetes

Byoungjae Kim (autru@uga.edu) 3/24 Tiemeyer Mgat1, requirement for complex/hybrid glycans, early arrestJoseph Moore (jmbard@uga.edu)Christine Oshansky (coshan@uga.edu)

3/31 Tiemeyer Exostoses, growth factor modulation

Narendra Tejwani (nejwani@uga.edu)Xiang Yong (yxiang@uga.edu)

4/14 Tiemeyer NOD factors

Lu Meng (lmeng@uga.edu) 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