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Organic Chemistry
4th
Edition
Paula Yurkanis Bruice
Chapter 23
Amino Acids,
Peptides,
and
Proteins
Irene Lee
Case Western Reserve University
Cleveland, OH
©2004, Prentice Hall
Peptides and proteins are polymers of amino acids linked
together by amide bonds
Aliphatic Side-Chain Amino Acids
O
+H3N
CH
C
O
O-
+H3N
H
CH
C
O-
CH 3
glycine
alanine
O
O
O
+H3N
+H3N
CH
C
CH
C
CH
C
CH
CH 3
CH 3
CH
CH 3
CH 3
valine
+H3N
O-
CH 2
CH
O-
leucine
CH 3
CH 2
CH 3
isoleucine
O-
Hydroxy-Containing Amino Acids
O
O
CH
C
CH 2
CH
OH
OH
CH 3
serine
threonine
+H3N
CH
C
O-
+H3N
O-
Sulfur-Containing Amino Acids
O
O
+H3N
+H3N
CH
C
CH 2
SH
CH
C
O-
O-
CH 2
CH 2
S
cysteine
CH 3
methionine
Acidic Amino Acids
O
O
+H3N
CH
C
O-
+H3N
CH 2
C
CH
C
O-
CH 2
O
CH 2
O-
C
aspartatic acid
O
glutamic acid
O-
Amides of Acidic Amino Acids
O
+H3N
CH
C
NH 2
asparagine
O-
+H3N
CH
C
O-
CH 2
CH 2
C
O
O
CH 2
C
NH 2
O
glutamine
Basic Amino Acids
O
O
+H3N
CH
C
O-
+H3N
CH
CH 2
CH 2
CH 2
CH 2
CH 2
CH 2
CH 2
NH
NH 3+
C
C
NH 2+
NH 2
lysine
arginine
O-
Benzene-Containing Amino Acids
O
O
+H3N
CH
C
CH 2
O-
+H3N
CH
C
CH 2
OH
phenylalanine
tyrosine
O-
Heterocyclic Amino Acids
C
O
O
O
O-
+H3N
CH
C
O-
+H3N
CH
CH 2
C
CH 2
+H2N
N
NH
proline
histidine
HN
tryptophan
O-
Configuration of Amino Acids
Acid–Base Properties of Amino Acids
An amino acid can never exist as an uncharged
compound
Some amino acids have ionizable hydrogens on their
side chains
The isoelectric point (pI) of an amino acid is the pH at
which it has no net charge
The pI of an amino acid that has an ionizable side chain
is the average of the pKa values of the similarly ionizing
groups
A mixture of amino acids can be separated by
electrophoresis on the basis of their pI values
Ninhydrin is used to detect the individual amino acids
A mixture of amino acids can also be separated on the
basis of polarity
Ion-exchange chromatography can be used to perform
preparative separation of amino acids
Negatively charged resin binds selectively to positively
charged amino acids
Ion-Exchange Chromatography
• Cations bind most strongly to cation-exchange
resins
• Anions bind most strongly to anion-exchange
resins
• An amino acid analyzer is an instrument that automates
ion-exchange chromatography
Resolution of Racemic Mixtures of Amino Acids
Formation of a Peptide
Peptide Bond
Formation of Disulfide Bonds
Disulfides can be reduced to thiols
The disulfide bridge in proteins contributes to the overall
shape of a protein
Because amino acids have two functional groups, a
problem arises when one attempts to make a particular
peptide
Strategy for Making a Specific Peptide Bond
Amino acids can be added to the growing C-terminal end
by repeating these two steps
When the desired number of amino acids has been
added to the chain, the protecting group can be
removed
An Improved Peptide Synthesis Strategy
The first step in determining the sequence of amino acids
in a peptide or protein is to cleave the disulfide bridges
The next step is to determine the number and kinds of
amino acids in the peptide or protein
protein
6 N HCl
100°C
24 h
amino acids
The N-terminal amino acid of a peptide or a protein can
also be determined by Edman degradation
The particular PTH-amino acid can be identified by
chromatography using known standards
The C-terminal amino acid can be identified by treating
the protein with carboxypeptidase
Cyanogen bromide causes the hydrolysis of the amide
bond on the C-side of a methionine residue
Secondary Structure of Proteins
Describe the conformation of segments of the backbone
chain of a peptide or protein
Three factors determine the choice of secondary
structure:
• the regional planarity about each peptide bond
• maximization of the number of peptide groups that
engage in hydrogen bonding
• adequate separation between nearby R groups
The a-Helix Is Stabilized by Hydrogen Bonds
Prolines are helix breakers
Two Types of b-Pleated Sheets
Most globular proteins have coil conformations
The tertiary structure is the three-dimensional
arrangement of all the atoms in the protein
The tertiary structure is defined by the primary structure
The stabilizing interactions include covalent bonds,
hydrogen bonds, electrostatic attractions, and
hydrophobic interactions
Disulfide bonds are the only covalent bonds that can
form when a protein folds
Proteins that have more than one peptide chain are
called oligomers