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Gentilucci, Amino Acids, Peptides, and Proteins
Amino Acids
Peptides and proteins are polymers of amino acids linked together by amide bonds
Aliphatic Side-Chain Amino Acids
O
O
+H3N
CH
C
+H3N
O-
C
O-
CH3
alanine
glycine H
CH
proline
Gentilucci, Amino Acids, Peptides, and Proteins
O
valine
+H 3 N
+H 3 N
CH
C
CH
C
O-
O-
leucine
CH
O
O
+H 3 N
isoleucine
CH 2
CH
C
O-
CH
CH 3
CH 3
CH
CH 2
CH 3
CH 3
CH 3
CH 3
2 stereocenters
HydroxyContaining Amino
Acids
O
O
+H 3 N
CH
C
+H 3 N
O-
CH 2
OH
serine
2 stereocenters
CH
C
CH
OH
O-
CH 3
threonine
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Gentilucci, Amino Acids, Peptides, and Proteins
O
O
Sulfur-Containing
Amino Acids
+H 3 N
+H 3 N
CH
C
CH
C
O-
OCH 2
CH 2
CH 2
cysteine
methionine
SH
S
CH 3
Acidic Amino Acids
O
O
+H3N
CH
+H3N
C
CH
C
O-
CH2
aspartatic acid
CH2
C
O-
glutamic acid
CH2
O
C
O-
O
O-
Gentilucci, Amino Acids, Peptides, and Proteins
O
O
Amides of Acidic
Amino Acids
+H3N
+H3N
CH
C
C
O-
CH2
CH2
glutamine
asparagine
C
CH
O-
CH2
O
C
NH2
O
NH2
O
O
+H3N
Basic
Amino
Acids
+H3N
CH
C
CH
C
O-
OCH2
CH2
CH2
CH2
lysine
CH2
CH2
NH
CH2
C
NH3+
NH2
arginine
NH2+
2
Gentilucci, Amino Acids, Peptides, and Proteins
O
O
BenzeneContaining Amino
Acids
+H3N
+H3N
CH
C
CH
C
O-
OCH2
CH2
tyrosine
phenylalanine
OH
Heterocyclic Amino Acids
O
O
O
+H3N
+H3N
C
CH
C
CH
O-
proline
O-
CH2
CH2
+H2N
C
O-
N
histidine
NH
HN
tryptophan
Gentilucci, Amino Acids, Peptides, and Proteins
Configuration of
Amino Acids
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Gentilucci, Amino Acids, Peptides, and Proteins
Acid–Base Properties
of Amino Acids
An amino acid can never exist as an
uncharged compound
The isoelectric point (pI)
of an amino acid is the pH at
which it has no net charge
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Gentilucci, Amino Acids, Peptides, and Proteins
Some amino acids have ionizable hydrogens on their side chains
The pI of an amino acid that has an ionizable side chain is the average of the pKa
values of the similarly ionizing groups
Gentilucci, Amino Acids, Peptides, and Proteins
A mixture of amino acids can be separated by electrophoresis on the basis of their
pI values
A mixture of amino acids can
also be separated on the basis of
polarity
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Gentilucci, Amino Acids, Peptides, and Proteins
Ninhydrin is used to detect
the individual amino acids
Gentilucci, Amino Acids, Peptides, and Proteins
Synthesis
Gabriel synthesis
with phtalimide
Malonic synthesis +
Gabriel reaction
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Gentilucci, Amino Acids, Peptides, and Proteins
Strecker Reaction
Gentilucci, Amino Acids, Peptides, and Proteins
Resolution of racemic mixtures
Enzymatic synthesis
Non chiral 2-oxopentanedioic gives optically pure glutamic acid
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Gentilucci, Amino Acids, Peptides, and Proteins
Formation of a Peptide
Peptide Bond
Gentilucci, Amino Acids, Peptides, and Proteins
Formation of
Disulfide Bonds
Disulfides can be reduced to thiols
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Gentilucci, Amino Acids, Peptides, and Proteins
Peptides
Angiotensin II: blood pressure regulating hormone
Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
Vasopressin: diuretic
hormone
Gentilucci, Amino Acids, Peptides, and Proteins
excitatory
neurotransmitter
inhibitory
neurotransmitter
Tyroid hormones
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Gentilucci, Amino Acids, Peptides, and Proteins
Antibiotic peptides
Vancomycin is a very large, aminoglycoside antibiotic produced by the
fermentation of the actinomycete bacteria Amycolatopsis orientalis. The main
target of this antibiotic is the D-alanyl-D-alanine terminal dipeptide of
peptidoglycan precursors, used by bacteria for constructing their cell walls.
Vancomycin binds with the substrate, not the enzyme: this is in contrast to the
way penicillin inhibits peptidoglycan synthesis.
Gentilucci, Amino Acids, Peptides, and Proteins
Opioid peptides
Peptide hormones
The disulfide bridge in proteins contributes to the overall shape of a protein
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Gentilucci, Amino Acids, Peptides, and Proteins
A problem arises
when one attempts
to make a
particular peptide
Strategy for making a
specific peptide: Gly-Ala
and ot Ala-Gly, Ala-Ala, etc
Gentilucci, Amino Acids, Peptides, and Proteins
Protection of N-terminus
+
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Gentilucci, Amino Acids, Peptides, and Proteins
Activation of COOH terminus
Gentilucci, Amino Acids, Peptides, and Proteins
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Gentilucci, Amino Acids, Peptides, and Proteins
Protecting group removal
Gentilucci, Amino Acids, Peptides, and Proteins
Merrifield
automated SPPS
Etc, etc
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Gentilucci, Amino Acids, Peptides, and Proteins
Gentilucci, Amino Acids, Peptides, and Proteins
Determination of protein sequence
1. Cleavage and identification of disulfide bridges
2. Acidic hydrolysis and
identification of a.a.
composition
6 N HCl
protein
amino acids
100°C
24 h
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Gentilucci, Amino Acids, Peptides, and Proteins
Gentilucci, Amino Acids, Peptides, and Proteins
3. Determination N-terminal amino acid by Edman degradation
The particular PTH-amino acid can be identified by
chromatography using known standards
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Gentilucci, Amino Acids, Peptides, and Proteins
4. Cyanogen bromide causes
the hydrolysis of the amide
bond on the C-side of a
methionine residue
5. The C-terminal amino acid can be
identified by treating the protein with
peptidases (eg carboxypeptidases)
Gentilucci, Amino Acids, Peptides, and Proteins
Proteins
Secondary structure
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 tertiary structure
It 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
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Gentilucci, Amino Acids, Peptides, and Proteins
The α-Helix Is Stabilized by Hydrogen Bonds
(prolines are helix
breakers)
Gentilucci, Amino Acids, Peptides, and Proteins
Two Types of β-Pleated Sheets
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Gentilucci, Amino Acids, Peptides, and Proteins
The tertiary structure is the three-dimensional arrangement of all the atoms in the
protein
Most globular proteins
have coil
conformations
Gentilucci, Amino Acids, Peptides, and Proteins
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