sign in sign up
<<
Home , Anomer, Disaccharide, Glycosidic bond, Gulose, Hexose

Fundamentals of Structure

1 Learning Objectives

 How are named?

 What are the different constituents of a glycan?

 How are these represented?

 Wha t confftiormations do residues addtopt in solltiution

 Why do glycan conformations matter?

2 Fundamentals of Glycan Structure

 CbhdCarbohydrate NlNomenclature   Structure  Fisher Representation  Cyclic Form  Chair Form  Derivatives  Reducing  Uronic Acids  Other Derivatives  Monosaccharide Conformation  Inter‐  Normal   Sequence Specificity and Recognition  Branching

3 Nomenclature

 The word ‘carbohydrate’ implies “hydrate of ” … Cn(H2O)m  (a monosaccharide) C6H12O6 … C6(H2O)6

 Sucrose (a ) C12H22O11 … C12(H2O)11

(a ) (C6H12O6)n… (C6(H2O)6)n  Not all have this formula … some have

(glucose + amine) …. C6H13O5N… ‐NH2 at the 2‐position of glucose

 N‐acetyl galactosamine ( + amine + acetyl group) …. C8H15O6N … ‐

NHCOCH3 at the 2‐position of galactose  Typical prefixes and suffixes used in naming carbohydrates  Suffix = ‘‐ose’ & prefix = ‘tri‐’, ‘tetr‐’, ‘pent‐’, ‘hex‐’  (a five carbon monosaccharide) or (a six carbon monosaccharide)  types  Monosaccharides with an group are called … e.g.,  Those with a keto group are called … e.g.,

4 Monosaccharides

 Struc ture

 Have a general formula CnH2nOn and contain a  Common monosaccharides have 3  9  Two molecules form the class of smallest monosaccharides … glyceraldehyde and dihydroxyacetone

CHO CH2OH CHOH O

CH2OH CH2OH Glyceraldehyde Dihydroxyacetone

5 Monosaccharides

 Glyceraldehyde has a chiral carbon CHO *CHOH * =chiral carbon … 2 stereoisomers CH2OH

 3‐Dimensional arrangement CHO CHO

HO H HOCH2 H CH2OH OH (R) (S)  2‐Dimensional representation CHO CHO CHO CHO H OH H OH HO H HO H

CH2OH CH2OH CH2OH CH2OH (R) (S) (D) (L)

6 Monosaccharides  ’s representation

 Arbitrarily assigned the dextrorotatory as D‐ glyceraldehyde, which fortuitously proved correct

CHO CHO H OH HO H

CH2OH CH2OH (D) (+) (L) (-)

Note: This does not mean that all D‐saccharides are dextrorotatory; likewise it does not mean that all D‐saccharides are also (R) in the Cahn‐Ingold‐Prelog system

7 Monosaccharides  ‘D’ monosaccharides CHO H OH CHO CHO CH OH H OH 2 HO H D-glyceraldehye H OH H OH

CH2OH CH2OH D- D- CHO CHO CHO CHO H OH HO H H OH HO H H OH H OH HO H HO H H OH H OH H OH H OH

CH2OH CH2OH CH2OH CH2OH D- D- D- D-

CHO CHO CHO CHO CHO CHO CHO CHO H OH HO H H OH HO H H OH HO H H OH HO H H OH H OH HO H HO H H OH H OH HO H HO H H OH H OH H OH H OH HO H HO H HO H HO H H OH H OH H OH H OH H OH H OH H OH H OH CH OH CH OH CH OH CH OH CH OH CH OH CH2OH 2 CH2OH 2 2 2 2 2 D- D- D-glucose D- D- D- D-galactose D-

 ‘D’ monosaccharides have the same configuration on their penultimate carbon as ‘D’ glyceraldehyde  Exactly similar series for ‘L’ monosaccharides starting with ‘L’ glyceraldehyde

 Likewise, similar series exists for ‘L’ and ‘D’ ketoses starting from dihydroxyacetone 8 Monosaccharides  ‘L’ ketoses

CH2OH O

CH2OH Dihydroxyacetone (no D- or L-form)

CH2OH O HO H

CH2OH L-

CH2OH CH2OH O O H OH HO H HO H HO H

CH2OH CH2OH L- L-

CH OH CH OH CH2OH CH2OH 2 2 O O O O H OH HO H H OH HO H H OH H OH HO H HO H HO H HO H HO H HO H CH OH CH OH CH2OH CH2OH 2 2 L- L-ftfructose L- L-tttagatose

9 Monosaccharides  Some Useful Information on Monosaccharides  D‐glucose is also called dextrose because it is dextrorotatory.  D‐glucose is the most abundant monosaccharide; it is present in most fruit juices  D‐glucose is also called blood sugar …… it is present in about 65 – 100 mg per 100 mL of blood  The dextrose solution for iv drip contains about 5% glucose + 0.15% saline (KCl)  is one of the monosaccharides present in disaccharide sucrose (table sugar) … the other is D‐glucose  Galactose is part of lactose (milk sugar)

10 Monosaccharides  Monosaccharides Are Typically not Linear (or Open‐Chain)  Remember from organic : and react with to give hemi‐ OH H O OH H + R' OR' R R CHO H H O OH H H H OH O H H CH CH H OH 3 3 anomeric carbon

CH3 6CH OH 6 6 1 CHO 2 CH2OH CH2OH H OH 5 OH 5 O H 5 O H O H H OH HO H H H H 1 1 + 1 H OH OH H OH H OH H H H 5 OH OH OH OH OH H H H H 6CH2OH OH OH OH -D-glucopyranose -D-glucopyranose (-D-glucose) (-D-glucose) HAWORTH Projections  What is an ?  How are ‐ and ‐ defined?  What is an ? Monosaccharides  Cyclic Structure of Ketoses  Similar cyclic structures exist for five membered saccharides … e.g., ribose.  These five membered cyclic are well known for nucleic acids … e.g., RNA (ribonucleic acid) and DNA (deoxyribonucleic acid)

1CH OH 2 6 O 1CH OH HOCH CH OH HOCH OH HOCH2 OH 2 2 O 2 2 O HO H 5 2 H H HO O HO H HO H H + H H OH OH CH2OH 5 H OH OH H OH H OH H 6 CH2OH -D-fructofuranose -D-fructofuranose D-fructose (-D-fructose) (-D-fructose)

HAWORTH Projections

CH OH HOCH OH HOCH2 O 2 2 O H H H H H H OH CH2OH OH H OH H 2-deoxy--D-fructofuranose 2-deoxy--D-fructofuranose (2-deoxy--D-fructose) (2-deoxy--D-fructose)

12 Monosaccharides  The Cyclic Form Assumes Different Conformations in Solution

CH2OH CH2OH O O H H H OH H H OH H OH H OH OH OH H H OH H OH

6 6 HOH C HOH2C O 2 O HO 5 H HO 5 H HO H 2 H HO H 2 OH OH 1 OH 1 H OH H H -D-glucopyranose -D-glucopyranose (-D-glucose) (-D-glucose) Chair Conformations

 Why is ‐D‐glucose the most common sugar in nature?

13 Monosaccharides  The Cyclic Form of D‐Galactose

CH2OH CH2OH O O OH H OH OH H H OH H OH H H OH H H H OH H OH

OH OH HOH C HOH2C O 2 O H H H H HO H H HO H OH OH OH H OH H H -D-galactopyranose -D-galactopyranose (-D-galactose) (-D-galactose) Chair Conformations

14 Monosaccharides  Mutarotation Arises From Cyclic and Open‐Chain Form Interconversion

CHO H OH HO H H OH H OH

CH2OH D-glucose

-D-glucopyranose -D-glucopyranose (-D-glucose) (-D-glucose) Optical activity O O []D = +112.2 []D = +18.7 O At equilibrium …. []D = +52.7 (Not an average! But weighted average; 63.6% of the ‐anomer)

15 Monosaccharide Derivatives  Reducing Sugars and Reducing End

CHO COOH

H OH H OH

HO H HO H

H OH Mild Oxidizing Agent H OH e.g., Tollen’s reagent H OH + H OH (Ag / NH3 –H2O

CH2OH CH2OH D‐Glucose D‐Gluconic Acid

 Reducing sugars and diabetes  Hemoglobin (Hb) is glycated ….. HbA1c levels should be < 6.5%

 Reaction of high glucose with NH2 group at the N‐terminus (Val) of Hb  Non‐enzymatic  Reflects Glc levels for the past 3 months (typical life of erythrocytes)

16 Monosaccharide Derivatives  Uronic Acids

CHO

H OH

HO H

H OH Specific in the bbdody H OH

CH2OH D‐Glucose D‐

 Biological relevance  Several other uronic acids occur in our body, e.g., D‐mannuronic acid (from D‐ mannose), L‐iduronic acid (from L‐idose), D‐galacturonic acid  Components of many  Add to the conformational complexity , e.g., L‐iduronic acid can exist in 2 O 1 4 several conformations other than chair – SO, S2, C4 and C1

17 Monosaccharide Derivatives  Glycosamines  Several aminosugars are known including D‐glucosamine, D‐mannosamine, D‐ galactosamine and N‐acetyl‐D‐glucosamine. These have a nitrogen at position 2

CHO CHO CHO CHO H N H H NH H NHCOCH H NH2 2 2 3 HO H HO H HO H HO H H OH H OH HO H H OH H OH H OH H OH H OH CH OH CH OH CH OH CH2OH 2 2 2 D-glucosamine D-mannosamine D-galactosamine N-acetyl-D-glucosamine

 Other Derivatives  Glycan Esters  The –OH groups can be esterified enzymatically, e.g., esters, acyl esters, and sulfate esters  Deoxy Sugars  The –OH group can be replaced with –H, ege.g., 2‐ (C‐2 deoxy), (C‐6 deoxy), etc.  Methylated Sugars  The –OH group can be methylated (methyltransferases), e.g., –OMe group at

C‐1 18 Monosaccharide Conformation  Finding the Most Stable Conformation of a Monosaccharide

CHO

H OH

HO H

H OH

H OH

CH2OH

D‐Glucose

19 Monosaccharide Conformation  Conformation of L‐Iduronic Acid

CHO

H OH

HO H

H OH

H OH

CH2OH D‐Glucose L‐Iduronic Acid

2 4 6 5 4 5 1 1 4 6 3 3 1 2

2 4 1 SO C1 C4

20 Generation of  The Inter‐Glycosidic Bond  The bond between two monosaccharides is the inter‐glycosidic bond  Fundamental linkage for generation of oligosaccharides  Any hydroxylicated molecule (e.g ., amino acids Tyr, Ser, Thr; OR alcohols cholesterol, cholic acid; OR saccharides) can form glycosidic bond  Most oligosaccharides form glycosidic bond between the anomeric carbon (C‐1) and other carbons (C‐2, C‐3, C‐4, and C‐6).  These different glycosidic linkages enhance the diversity of glycans  Glycosidic bond induces directionality in the saccharide chain, i.e., non‐reducing end  reducing end  Glycosidic bonds make the oligomer flexible

21 Generation of Oligosaccharides  Sucrose’s Inter‐Glycosidic Bond is Different  Sucrose (table sugar) is a disaccharide made from ‐D‐glucose and ‐D‐fructose, where the inter‐glycosidic bond is ‐1,2

6 CH2OH 5 O

1 OH OH 2

OHO

6 HOCH 2 O ‐1,2‐interglycosidic bond 5 OH 2 CH OH 1 2 OH

 How do we find out which atoms are connected in polysaccharides and what is their orientation?  How do we know what conformation does a sugar adopt?

22 Generation of Oligosaccharides  Lactose  Lactose (milk sugar) is a disaccharide made from ‐D‐galactose and D‐glucose, where the inter‐glycosidic bond is ‐1,4

CH2OH O OH

CH2OH OH ‐1,4‐interglycosidic O OH O bond OH OH

OH

? … cow’s milk … 4 –6% lactose … some infants, most blacks and many Orientals have low level of , which hydrolyzes the (1,4) bond of lactose … lactose accumulates in colon where bacterial

produces large quantities of CO2, H2 and organic acids 23 Generation of Oligosaccharides  Sequence Specificity and Recognition  Is lactose (D‐galactose‐14)‐D‐glucose) is same as D‐glucose‐14)‐D‐ galactose?

2

2

 Remember! D‐glucose is consumed by our body; L‐glucose is left untouched!

24 Generation of Oligosaccharides  Branching is a Unique Structure Only Present in Carbohydrates  Two inter‐glycosidic linkages to the same monosaccharide results in branching  Branching is not found in proteins, nucleic acids and …. Only in carbohydrate

Taken from ‘Essentials of Glycobiology.’ Edited by Varki, A.; et al.; Cold Spring Harbor Laboratory Press, New York, 2009, pg. 36. 25