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Amino Acids and Peptides
Precursors of Proteins
Proteins(Amino Acids)
H2N C C
R1
H
N C COOH
R2
H
H2N C C
R1
H
O
N C COOH
R2
H H
O
OH
H
H
Amino Acid Amino Acid Protein
H2O
Only 20 naturally-occurring amino acids
Only linear structures
Functions of Proteins I
• Catalysts and Metabolic Regulation – Enzymes• Protection
– Serum antifreeze proteins– Blood coagulation– Antibodies
• Membrane Transport – Nutrients• Signal Transduction – Cell Surface Receptors• Structural Support – Collagen
Functions of Proteins II
• Coordinated Motion – Muscle Contraction• Genetic Regulation – DNA Binding Proteins• Transport – Hemoglobin• Generation and Transport of Nerve Impulses• Nutrient Storage
– Seed proteins– Casein in milk
Function of proteins largely due to properties of constituent amino acids
Standard Amino Acids (20)
NH
COOH
Proline
H2N C COOH
R
H
-Amino Acid
Stereochemistry Review
Optical Activity
Figure 4-9
Diagram of a Polarimeter
Rotation of Plane of Polarized Light
Dextrorotatory(rotation to the right) =
“d” or “+”
Levorotatory(rotation to the left) =
“l” or “-”
Empirical
Optically Active Molecules are Asymmetric
(i.e. not superimposible on their mirror image)
Chiral (Asymmetric) Carbon
Four different substituentsStereoisomers
C atoms of amino acids (except glycine) are asymmetric centers!
Chiral Centers Give Rise to Enantiomers
(non-superimposible mirror images)
Distinguishing Stereoisomers
• Rotation of plane of polarized light (not related to absolute configuration)
• Cahn-Ingold-Prelog Method (R/S)
• Fischer Method (projections)
Cahn-Ingold-Prelog Method (R/S)(1956)
COOC NH3
CH2OH
+-
H
(S-2-amino-glycerate)S-Serine
CCOOH3N
CH2OH
+ -
H
(R-2-amino-glycerate)R-Serine
Fischer Convention(1891)
Protein Amino Acids
Fischer Method/Projections (L/D)
H3N C
COO
H
CH2OH
NH3C
COO
H
CH2OH
(S- 2-AMINO-GLYCERATE) (R- 2-AMINO-GLYCERATE)L- SERINE D-SERINE
H3N C
COO
H
CH2OH
NH3C
COO
H
CH2OH
H3N
COO
H
CH2OH
NH3
COO
H
CH2OH
L--Amino Acids
H3N C
COO
H
CH2OH
COOC
CH2OH
H3N
H
Chirality and Biochemistry
Life is Based on Chiral Molecules
Biosynthetic processes almost invariably produce pure
stereoisomers – e.g. L-amino acids
Biological D-amino acids: Bacterial Cell Wall
Pharmaceutical Industry
Racemic Mixtures
Figure 4-12
Benign
Figure 4-13
Devastating
Chiral Synthesis
Goal of Organic Chemistry
Amino Acids
Non-Polar Hydrophobic Amino Acids
Aromatic Amino Acids
H3N C COO–
H
CH2
CH2
S
CH3
H3N C COO–
H
NH
H3N C COO–
H
NH2
COO–CH2 CH2
Proline
PhenylalanineTryptophanMethionine
Non-Polar Polar
H3N C COO–
H
CH2
OH
H3N C COO–
H
CH2
C
NH2
O
H3N C COO–
H
CH2
CH2
C
NH2
O
GlutamineAsparagineTyrosine
Polar Amino Acids
Negatively Charged (Acidic) Amino Acids
Positively Charged (Basic) Amino Acids
Notation for 20 Standard AAs
Three-Letter One-Letter
Amino Acid Symbol Symbol
Alanine Ala A
Arginine Arg R
Asparagine Asn N
Aspartate Asp D
Cysteine Cys C
Glutamate Glu E
Glutamine Gln Q
Glycine Gly G
Histidine His H
Isoleucine Ile I
Leucine Leu L
Lysine Lys K
Methionine Met M
Phenylalanine Phe F
Proline Pro P
Serine Ser S
Threonine Thr T
Tryptophan Trp W
Tyrosine Tyr Y
Valine Val V
Figure 4-8
Greek Nomenclature
Dipolar Ions(Zwitterions)
Amino Acids can be Buffers
Histidine is particularly important for biological function
Isoelectric point (pI)
pH at which the molecule has a net charge of 0.
pI = pKa1 + pKa2
2
– Using the pKa’s on either side of the neutral species
The Peptide Bond
Peptide Bonds
Linear Polymers
N-Terminus
C-Terminus
Peptides
Dipeptides
Tripeptides
Oligopeptides
Polypeptides
Diversity
Number = 20n
Variations in length and sequence contribute to the diversity of shapes and biological functions of
proteins
Nomenclature of Peptides(Primary Structure)
L-alanyl-L-seryl-L-aspartic acid[aspartate]
AlanylserylaspartateAlaSerAsp
ASD
Diversity(Tripeptide: 3 x 2 x 1 = 6
arrrangements)
Ala Ser Asp Ala Asp Ser
Ser Ala Asp Ser Asp Ala
Asp Ser Ala Asp Ala Ser
For 20 amino acids (small peptide):
20! = 2.43 x 1018
Selenocysteine: the 21st Amino Acid
H3N C COO–
H
CH2
SH
H3N C COO–
H
CH2
OH
H3N C COO–
H
CHH3C OH
CysteineThreonineSerine
Pyrrolysine: the 22nd Amino Acid
H3N C COO–
H
CH2
CH2
CH2
CH2
NH3+
H3N C COO–
H
CH2
CH2
CH2
NH
CH2N NH2
H3N C COO–
H
CH2
NH
HN
HistidineArginine
+
Lysine
Protein Amino Acid Derivatives
Figure 4-14
Some Modified Peptidyl Amino Acids
Disulfide Bond Formation(Cystine)
CH
O
CH2
SH
SH
CH2
CHC
O
C
N
H
N
H
CH
O
CH2
S
S
CH2
CHCO
C
N
H
N
H
1/2 O2
Disulf ide Bond
H2O
Cysteine
Cysteine
Cystine
Hydroxylation
NH2
COO–
H
OH
4–hydroxyproline
OH
NH3
CH2
CH
CH2
CH2
CHH3N COO–
5–hydroxylysine
Phosphorylation
Phosphoserine Phosphohistidine
O P O–
O
O–CH2
CHH2N COO–+
N
N
CH2
P O–
O
O–
CHH2N COO–+
Acetylation
H3N C
COO–
H
CH2
CH2
CH2
CH2
NH
C
CH3
O
Acetyllysine
Formylation(amino terminal methionine)
CH 3
S
CH 2
CH 2
CHNH C
O
HC
O
Other Modifications
• Methylation (methyl group)
• Glycosylation (sugar)
Figure 4-15
Biologically Active Amino Acid Derivatives
Non-protein Amino Acids
H3N C
COO–
NH3
CH2
COO–
CH3N
CH2
COO–
CH2
C H3N
CH2
CH2
CH2 H
H
H
H
H
Ornithine -alanine (GABA)-aminobutyric acid
Green Fluorescent Protein
Box 4-3 figure 1
Aequorea victoria
Box 4-3 figure 2
Green Fluorescence Protein (GFP)
• GFP cloned in the early 1990s and expressed in E. coli.
http://www.conncoll.edu/ccacad/zimmer/GFP-ww/GFP2.htm
GFP-like and GFP variants
• GFP-like proteins identified in non-bioluminescent organism (i.e. corals)
• Mutants with faster and brighter fluorescence have since been identified.
http://www.conncoll.edu/ccacad/zimmer/GFP-ww/GFP2.htm
In vivo Imaging
Spatial-temporal imaging of bacterial infection
Zhao, M. et al. PNAS. 2001; 98(17): 9814-9818.
Cool Green Things!
http://www.conncoll.edu/ccacad/zimmer/GFP-ww/GFP4.htm