Guest%20Lecturer:%20Prof.%20Jonathan%20L.%20Sessler

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Guest Lecturer Prof. Jonathan L. Sessler
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Carbohydrates

• Carbohydrate A polyhydroxyaldehyde, a
  polyhydroxyketone, or a compound that gives
  either of these compounds after hydrolysis.
• Monosaccharide A carbohydrate that cannot be
  hydrolyzed to a simpler carbohydrate.
• They have the general formula CnH2nOn, where n
  varies from 3 to 8.
• Aldose a monosaccharide containing an aldehyde
  group.
• Ketose a monosaccharide containing a ketone
  group.

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Monosaccharides

• Monosaccharides are classified by their number of
  carbon atoms

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Names and Structures

• Monosaccharide aldehyde or ketone containing at
  least two additional hydroxy groups
• Aldehyde - aldose
• Ketone - ketose
• Also named by number of carbons

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Monosaccharides

• There are only two trioses
• Often the designations aldo- and keto- are
  omitted and these compounds are referred to
  simply as trioses, tetroses, and so forth.
• Although these designations do not tell the
  nature of the carbonyl group, they at least tell
  the number of carbons.

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Monosaccharides

• Glyceraldehyde contains a stereocenter and exists
  as a pair of enantiomers.

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Fischer Projections

• Fischer projection A two dimensional
  representation for showing the configuration of
  carbohydrates.
• Horizontal lines represent bonds projecting
  forward.
• Vertical lines represent bonds projecting to the
  rear.
• The only atom in the plane of the paper is the
  stereocenter.
• The more highly oxidized carbon is shown at the
  top.

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D,L Monosaccharides

• In 1891, Emil Fischer made the arbitrary
  assignments of D- and L- to the enantiomers of
  glyceraldehyde.
• This is an older stereochemical designation that
  is still used for amino acids and sugars that
  antedates the Cahn-Ingold-Prelog R/S system.

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D,L Monosaccharides

• According to the conventions proposed by Fischer
• D-monosaccharide A monosaccharide that has the
  same configuration at its penultimate carbon as
  D-glyceraldehyde that is, its -OH is on the
  right when written as a Fischer projection.
• L-monosaccharide A monosaccharide that has the
  same configuration at its penultimate carbon as
  L-glyceraldehyde that is, its -OH is on the left
  when written as a Fischer projection.

Note that this designation refers to only one
carbon in molecules that often have many
stereocenters.
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Names and Structures

• Sugars are optically active (D vs. L)
• Almost all naturally occurring sugars are D

Fischer projections make it easy to see the
last carbon. It is one reason we use them!
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D,L Monosaccharides

• Here are the two most abundant D-aldotetroses and
  the two most abundant D-aldopentoses in the
  biological world

You must know these compounds and their
chemistry (and their normal Fischer and Haworth
projections)
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D,L Monosaccharides

• And the three most abundant hexoses

You must know these compounds and their chemistry
(and their normal Fischer and Haworth
projections)
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Amino Sugars

• Amino sugar A sugar that contains an -NH2 group
  in place of an -OH group.
• Only three amino sugars are common in nature
• N-Acetyl-D-glucosamine is a derivative of
  D-glucosamine.

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Physical Properties

• Monosaccharides are colorless crystalline solids,
  very soluble in water, but only slightly soluble
  in ethanol.
• sweetness relative to sucrose

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Cyclic Structure

• Monosaccharides have hydroxyl and carbonyl groups
  in the same molecule and those with five or more
  carbons exist almost entirely as five- and
  six-membered cyclic hemiacetals.
• Anomeric carbon The new stereocenter created as
  a result of cyclic hemiacetal formation.
• Anomers Carbohydrates that differ in
  configuration at their anomeric carbons.

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Haworth Projections

• Haworth projections
• Five- and six-membered hemiacetals are
  represented as planar pentagons or hexagons, as
  the case may be, viewed through the edge.
• They are most commonly written with the anomeric
  carbon on the right and the hemiacetal oxygen to
  the back right.
• The designation ?- means that the -OH on the
  anomeric carbon is cis to the terminal -CH2OH
  ?- means that it is trans to the terminal
  -CH2OH.

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Haworth Projections
Hint Drawn this way, the non-D OHs to the
right in a standard Fischer Projection go down
in the Haworth Projection
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Haworth Projections

• Six-membered hemiacetal rings are shown by the
  infix -pyran-.
• Five-membered hemiacetal rings are shown by the
  infix -furan-.

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Conformational Formulas

• Five-membered rings are so close to being planar
  that Haworth projections are adequate to
  represent furanoses.

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Conformational Formulas

• Other monosaccharides also form five-membered
  cyclic hemiacetals.
• Here are the five-membered cyclic hemiacetals of
  D-fructose.

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Ascorbic Acid (Vitamin C)

• L-Ascorbic acid (vitamin C) is synthesized both
  biochemically and industrially from D-glucose.

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Ascorbic Acid (Vitamin C)

• L-Ascorbic acid is very easily oxidized to
  L-dehydroascorbic acid.
• Both are physiologically active and are found in
  most body fluids.

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Conformational Formulas

• For pyranoses, the six-membered ring is more
  accurately represented as a chair conformation.

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Conformational Formulas

• If you compare the orientations of groups on
  carbons 1-5 in the Haworth and chair projections
  of ?-D-glucopyranose, you will see that in each
  case they are up-down-up-down-up respectively.

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Cyclic Forms of Monosaccharides - details

• Sugars often have a choice in forming
  intramolecular hemiacetals

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Cyclic Forms of Monosaccharides - cont.

• Sugars form intramolecular hemiacetals
• New stereocenter formed at anomeric carbon
• For D sugars, S centers are termed ? and R
  centers are ?
• These diastereomers are termed anomers

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Cyclic Forms of Monosaccharides - cont.
Which conformation do you think is the most
stable? Why?
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Mutarotation

• Mutarotation The change in specific rotation
  that occurs when an ? or ? form of a carbohydrate
  is converted to an equilibrium mixture of the two.

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Mutarotation of Monosaccharides

• Conversion of anomers is termed mutarotation and
  goes through an open chain form

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Glycosides

• Glycoside A carbohydrate in which the -OH of the
  anomeric carbon is replaced by -OR.
• methyl ?-D-glucopyranoside (methyl ?-D-glucoside)

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Glycosides

• Glycosidic bond The bond from the anomeric
  carbon of the glycoside to an -OR group.
• Glycosides are named by listing the name of the
  alkyl or aryl group bonded to oxygen followed by
  the name of the carbohydrate with the ending -e
  replaced by -ide.
• methyl ?-D-glucopyranoside
• methyl ?-D-ribofuranoside

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N-Glycosides

• The anomeric carbon of a cyclic hemiacetal also
  undergoes reaction with the N-H group of an amine
  to form an N-glycoside.
• N-glycosides of the following purine and
  pyrimidine bases are structural units of nucleic
  acids.

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N-Glycosides

• The b-N-glycoside formed between D-ribofuranose
  and cytosine.

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Reduction to Alditols

• The carbonyl group of a monosaccharide can be
  reduced to an hydroxyl group by a variety of
  reducing agents, including NaBH4 and H2/M.

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Reduction to Alditols

• Other alditols common in the biological world are

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Oxidation to Aldonic Acids

• The -CHO group can be oxidized to -COOH (reducing
  sugars). Oxidizing agents for this transformation
  include bromine in aqueous CaCO3 (Br2, CaCO3,
  H2O), copper(II) in base (Fehlings solution),
  and Tollens solution (Ag(NH3)2). -- Copper
  bricks and silver mirrors!

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Oxidation to Aldonic Acids

• 2-Ketoses (also reducing sugars) are also
  oxidized to aldonic acids. 3-Ketoses, 4-ketoses,
  etc. are not. Nor are compounds where the
  carbonyl is tied up in a glycosidic bond.
• Under the conditions of the oxidation, 2-ketoses
  equilibrate with isomeric aldoses (Step 1 2) by
  keto-enol tautomerization. The aldose is then
  oxidized to the aldonic acid (Step 3).

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Oxidation to Uronic Acids

• Enzyme-catalyzed oxidation of the terminal -OH
  group gives a -COOH group.

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Oxidation to Uronic Acids

• In humans, D-gluconic acid is an important
  component of the acidic polysaccharides of
  connective tissue.
• It is also used by the body to detoxify foreign
  hydroxyl-containing compounds, such as phenols
  and alcohols one example is the intravenous
  anesthetic propofol.

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Carbohydrates
End of Chapter 25
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Triglycerides
Beeswax contains a component which is an ester of
a fatty acid
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A Triglyceride
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Soaps and Detergents
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Steroids
Tetracycylic ring system characteristic of
steroids
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Cholesterol
Human gallstones are almost pure cholesterol
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(continued)
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Biosynthesis of Cholesterol
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Amino Acids

• Amino acid A compound that contains both an
  amino group and a carboxyl group.
• - ?-Amino acid An amino acid in which the amino
  group is on the carbon adjacent to the carboxyl
  group.
• Although neutral ?-amino acids are commonly
  written in the unionized form, they are more
  properly written in the zwitterion (internal
  salt) form. Needless to say, adding acid or base
  can lead to conversion to other forms.

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Chirality of Amino Acids

• With the exception of glycine, all
  protein-derived amino acids have at least one
  stereocenter (the ?-carbon) and are chiral.
• the vast majority have the L-configuration at
  their ?-carbon.

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Nonpolar side chains
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Polar side chains
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Acidic Basic Side Chains
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Some Other Amino Acids
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Acid-Base properties
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Acid-Base Properties
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Acidity ?-COOH Groups

• The average pKa of an ?-carboxyl group is 2.19,
  which makes them considerably stronger acids than
  acetic acid (pKa 4.76).
• The greater acidity is accounted for by the
  electron-withdrawing inductive effect of the
  adjacent -NH3 group.

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Acidity side chain -COOH

• Due to the electron-withdrawing inductive effect
  of the ?-NH3 group, side chain -COOH groups are
  also stronger than acetic acid.
• The effect decreases with distance from the
  ?-NH3 group. Compare
• ?-COOH group of alanine (pKa 2.35)
• ?-COOH group of aspartic acid (pKa 3.86)
• ?-COOH group of glutamic acid (pKa 4.07)

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Acidity ?-NH3 groups

• The average value of pKa for an ?-NH3 group is
  9.47, compared with a value of 10.76 for a 1
  alkylammonium ion.

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The Guanidine Group of Arg

• This is a special side chain.
• The basicity of the guanidine group is attributed
  to the large resonance stabilization of the
  protonated form relative to the neutral form.

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Basicity - Imidazole Group

• The imidazole group is a heterocyclic aromatic
  amine.

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Titration of Amino Acids

• Titration of glycine with NaOH.

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Isoelectric Point

• Isoelectric point (pI) The pH at which an amino
  acid, polypeptide, or protein has a total charge
  of zero.
• The pH for glycine, for example, falls between
  the pKa values for the carboxyl and amino groups.

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Isoelectric Point
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Isoelectric Point
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Electrophoresis

• Electrophoresis The process of separating
  compounds on the basis of their electric charge.
• electrophoresis of amino acids can be carried out
  using paper, starch, polyacrylamide and agarose
  gels, and cellulose acetate as solid supports.

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Electrophoresis

• A sample of amino acids is applied as a spot on
  the paper strip.
• An electric potential is applied to the electrode
  vessels and amino acids migrate toward the
  electrode with charge opposite their own.
• Molecules with a high charge density move faster
  than those with low charge density.
• Molecules at their isoelectric point remain at
  the origin.
• After separation is complete, the strip is dried
  and developed to make the separated amino acids
  visible.
• After derivitization with ninhydrin, 19 of the 20
  amino acids give the same purple-colored anion
  proline gives an orange-colored compound.

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Electrophoresis

• The reagent commonly used to detect amino acid is
  ninhydrin.

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Polypeptides Proteins

• In 1902, Emil Fischer proposed that proteins are
  long chains of amino acids joined by amide bonds
  to which he gave the name peptide bonds.
• Peptide bond The special name given to the amide
  bond between the ?-carboxyl group of one amino
  acid and the ?-amino group of another.

Peptide bonds
Peptide bonds
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Serinylalanine (Ser-Ala)
A dipeptide
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Peptides

• Peptide The name given to a short polymer of
  amino acids joined by peptide bonds they are
  classified by the number of amino acids in the
  chain.
• Dipeptide A molecule containing two amino acids
  joined by a peptide bond.
• Tripeptide A molecule containing three amino
  acids joined by peptide bonds.
• Polypeptide A macromolecule containing many
  amino acids joined by peptide bonds.
• Protein A biological macromolecule of molecular
  weight 5000 g/mol or greater, consisting of one
  or more polypeptide chains.

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Writing Peptides

• By convention, peptides are written from the
  left, beginning with the free -NH3 group and
  ending with the free -COO- group on the right.

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Writing Peptides

• The tetrapeptide Cys-Arg-Met-As
• At pH 6.0, its net charge is 1.

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Primary Structure

• Primary structure The sequence of amino acids in
  a polypeptide chain read from the N-terminal
  amino acid to the C-terminal amino acid
• Amino acid analysis
• Hydrolysis of the polypeptide, most commonly
  carried out using 6M HCl at elevated temperature.
• Quantitative analysis of the hydrolysate by
  ion-exchange chromatography.

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Ion Exchange Chromatography

• Analysis of a mixture of amino acids by ion
  exchange chromatography

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Edman Degradation

• Edman degradation Cleaves the N-terminal amino
  acid of a polypeptide chain.

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Edman Degradation Mechanism It will be on the
final!
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Cytochrome C
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And, we are done!!