chamras chemistry 106 lecture notes chapter 24: amino...
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Chamras Chemistry 106 Lecture Notes
Chapter 24: Amino Acids, Peptides, and Proteins General Formula: α-Amino Acids: (n = 1) Example: Glycine Alanine Valine Amino Acids and Proteins:
AA’s are the building blocks of proteins
NO
OH
(R)H
H(R')
n
NO
OH
H
H
NO
OH
H
H
NO
OH
H
H
NH
O
NNH
O
HN
O
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Chirality of α-Amino Acids: Example: (S) (S) ***L-amino acids are usually what is found in the nature. Standard Amino Acids: 20 amino acids found in nearly all proteins Types of Standard Amino Acids: (Based on the nature of the side chain [the R group]) The side chain (the R group): (For more details please see Table 24-2)
1. is a non-polar H or alkyl group: (7) Gly, Ala, Val*, Leu*, Ile*, Phe*, Pro
2. contains an –OH: (3) Ser, Thr*, Tyr
3. contains S: (2) Cys, Met*
4. contains non-basic N: (3) Asn, Gln, Trp*
5. is acidic: (2) Asp, Glu
6. is basic: (3) Lys*, Arg*, His* Essential Amino Acids: Incomplete Proteins:
NO
OH
H
H
R
NO
OH
H
H
COOH
R
H2N H
CHO
CH2OH
HO H
L-glyceraldehydeL-amino acid
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Acid-Base Properties of Amino Acids: Summary of Physical Properties: Amino acids…
1. Have high MP (MP>200oC) 2. Are H2O soluble 3. Are more polar than simple amines and carboxylic acids. 4. Are less acidic than most carboxylic acids and less basic than most amines.
Acidic part = protonated amino group Basic part = deprotonated carboxylic group
Carboxylic functional group: Amino functional group: N
H
H
N
H
H
Avg. pH = 9-10H
O
OH
O
O–
Avg. pH = 2
NO
OH
H
H
R
NO
O
H
H
RH
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Titration curve for simple amino acids (lacking acidic or basic side chains): Electrophoresis: A technique for separation, based on the net charges of amino acids.
pH
Equivalents of OH– added
2
9
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Syntheses of Amino Acids:
1. Reductive Amination: (α-keto acid α-amino acid) General Equation: Example:
2. Amination of α-halo acid: (α-bromo acid α-amino acid) General Equation: *Stereochemistry: Example:
O
N
O
OHH
O
1. NH3 (xs)
2. H2, Pd
O
OH NH3
(excess)
R
NH
NH4
H2
PdR
NHH
O
R
O
O
O
O
!-amino acid!-ketoacid imine
NH4
O
OH
(HVZ)
NH3 (xs)R
NHH
R
O
O
!-amino acid
carboxylic acid
1. Br2, PBr3
2. H2O
O
OHR
Br
NH4
(HVZ)
NH3 (xs)1. Br2, PBr3
2. H2O
NH4
H2N
O O
O
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3. The Gabriel-malonic ester synthesis: Last Step: Hydrolysis of: esters & phthalimide, followed by protonation of amine. Phthalimide operates as a protected amine until it gets hydrolyzed.
4. The Strecker synthesis: Aldehyde + ammonia + HCN Amino acid (in acidic medium)
O
OO
O
NO O Cl
1. OH–
2.O
O O
O
N
O
O
H3O+OH
O
NH3
R H
O
HN
H
H
+ +
H
C
N
H3O+
HR
N
O
OHH
HH
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Mechanism:
1. Imine formation by acetaldehyde and ammonia 2. Addition of cyanide 3. Hydrolysis of nitrile into carboxylic acid
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Reactions of Amino Acids:
1. Esterification of the carboxyl group: Amino acid Amino ester (Similar to Fischer Esterification) Product = Amino ester
2. Acylation of the amino group: Amino Acid Amide Reacts with acid anhydride or acid chloride
3. Reaction with ninhydrin: (Ruhemann’s Purple)
+
R
N
O
OHH
H
OH
OH
O
O
2O
O
O
O
N
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4. Formation of Peptide bonds:
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Peptide Structure and Nomenclature: Structure:
Peptide bond (linkage):
N-Terminus:
C-Terminus:
Residue: Types of Peptides; Dipeptide: (2) Oligopeptide: (5-10) Polypeptide: (MW <5000g.mol–1) Protein: (6000 < MW < 40,000,000) g.mol–1
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Nomenclature: Template: { (______yl)n ________ine} Examples:
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Protein Structure Determination:
General Approach: breaking down the protein into residues.
1. Breaking the disulfide bonds: Results in breaking the cross-links between chains containing cysteines.
Agent: Peroxyformic acid
2. Separation and purification into individual chains. 3. Hydrolysis of individual chain: Results in separation of all residues present in the
individual chain.
Agent: Boiling 6M HCl(aq), 24 Hrs.
4. Passing the hydrolyzed mixture through an analyzer: Results in identification of the amino acids present.
3’. Terminal Residue Analysis: Alternatively, in order to identify the sequence of amino acids in the chain, one residue at a time could be hydrolyzed and identified.
a) N-Terminus Analysis: Edman Degradation & Sanger Method
Agent: Phenyl isothiocyanate
S S
SO3H
HO3SH O
O
OH
NC
S
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Mechanism: (Edman)
Mechanism: (Sanger)
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b) C-Terminus Analysis: Results in cleavage of the C-terminal amino acid.
Agent: Carboxypeptidase, H2O
c) Partial Hydrolysis:
Agents: i) Dilute acid:
ii) Trypsin: Cleaves at the carboxyl groups of basic amino acids (lysine and arginine)
iii) Chymotrypsin: Cleaves at the carboxyl groups of aromatic amino acids (phenylalanine, tyrosine, and, tryptophan)
Examples:
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Solution Phase Peptide Synthesis: Based on the following reaction: Starts at the N-terminus (left to right):
R Cl
O
R'N
H
H
R N
O
H
R'
O Cl
O
HN
H O
OH
(Z–Cl)
O Cl
O
HN
H O
OH
H2, Pd