amino acids gentilucci 2... · 2007. 4. 16. · gentilucci, amino acids, peptides, and proteins...
TRANSCRIPT
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Peptides and proteins are polymers of amino acids linked together by amide bonds
Amino Acids
Gentilucci, Amino Acids, Peptides, and Proteins
Aliphatic Side-Chain Amino Acids
+H3N CH C
H
O-
O
+H3N CH C
CH3
O-
O
glycine alanine proline
+H 3N CH C
CH
O-
O
CH 3
CH 3
+H 3N CH C
CH 2
O-
O
CH CH 3
CH 3
+H 3N CH C
CH
O-
O
CH 3
CH 2
CH 3
valine
leucineisoleucine
Hydroxy-Containing Amino Acids
+H 3N CH C
CH
O-
O
OH
CH 3
+H 3N CH C
CH 2
O-
O
OH
serine threonine
Gentilucci, Amino Acids, Peptides, and Proteins
2 stereocenters
2 stereocenters
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Sulfur-Containing Amino Acids
+H 3N CH C
CH 2
O-
O
SH
+H 3N CH C
CH 2
O-
O
CH 2
S
CH 3
cysteinemethionine
Acidic Amino Acids
+H3N CH C
CH2
O-
O
C
O-
O
+H3N CH C
CH2
O-
O
CH2
C
O-
O
aspartatic acidglutamic acid
Gentilucci, Amino Acids, Peptides, and Proteins
Amides of Acidic Amino Acids +H3N CH C
CH2
O-
O
CH2
C
NH2
O
+H3N CH C
CH2
O-
O
C
NH2
O
asparagine glutamine
Basic Amino Acids
+H3N CH C
CH2
O-
O
CH2
CH2
CH2
NH3+
+H3N CH C
CH2
O-
O
CH2
CH2
NH
C
NH2
NH2+
lysine arginine
Gentilucci, Amino Acids, Peptides, and Proteins
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Benzene-Containing Amino Acids +H3N CH C
CH2
O-
O
+H3N CH C
CH2
O-
O
OH
phenylalanine tyrosine
+H2N
C O-
O
+H3N CH C
CH2
O-
O
N
NH
+H3N CH C
CH2
O-
O
HN
proline histidine tryptophan
Heterocyclic Amino Acids
Gentilucci, Amino Acids, Peptides, and Proteins
Configuration of Amino Acids
Gentilucci, Amino Acids, Peptides, and Proteins
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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 atwhich it has no net charge
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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 pKavalues 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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Ninhydrin is used to detect the individual amino acids
Gentilucci, Amino Acids, Peptides, and Proteins
Synthesis
Gabriel synthesiswith phtalimide
Malonic synthesis + Gabriel reaction
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Strecker Reaction
Gentilucci, Amino Acids, Peptides, and Proteins
Enzymatic synthesisNon chiral 2-oxopentanedioic gives optically pure glutamic acid
Resolution of racemic mixtures
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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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Angiotensin II: blood pressure regulating hormone
Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
Vasopressin: diuretichormone
Peptides
Gentilucci, Amino Acids, Peptides, and Proteins
Gentilucci, Amino Acids, Peptides, and Proteins
inhibitory neurotransmitter
excitatory neurotransmitter
Tyroid hormones
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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
Antibiotic peptides
The disulfide bridge in proteins contributes to the overall shape of a protein
Gentilucci, Amino Acids, Peptides, and Proteins
Opioid peptides
Peptide hormones
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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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Activation of COOH terminus
Gentilucci, Amino Acids, Peptides, and Proteins
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Protecting group removalGentilucci, Amino Acids, Peptides, and Proteins
Merrifieldautomated SPPS
Etc, etc
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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
protein
6 N HCl
100°C24 h
amino acids
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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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5. The C-terminal amino acid can be identified by treating the protein with peptidases (eg carboxypeptidases)
4. Cyanogen bromide causes the hydrolysis of the amide bond on the C-side of a methionine residue
Gentilucci, Amino Acids, Peptides, and 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
Proteins
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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(prolines are helix breakers)
Gentilucci, Amino Acids, Peptides, and Proteins
The α-Helix Is Stabilized by Hydrogen Bonds
Two Types of β-Pleated Sheets
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The tertiary structure is the three-dimensional arrangement of all the atoms in the protein
Gentilucci, Amino Acids, Peptides, and Proteins
Most globular proteins have coil conformations
Gentilucci, Amino Acids, Peptides, and Proteins