Chem 109 C
Fall 2014
Armen Zakarian
Office: Chemistry Bldn 2217!
http://web.chem.ucsb.edu/~zakariangroup/courses.html!
Amino acids, Peptides, Proteins: Introduction
Chapter 22
O
R
OH
NH2
!-amino acid
O
R
O
OH
+
H2N R
- H2O
R
N
H
R
peptide bond = amide bond
2
Proteins: Function
3
Proteins: Structural
Histone Protein Structure:
DNA packaging
4
Proteins: Protective
botulinum toxin (botox) structure
most toxic substance known
5
Amino acids, Peptides, Proteins: Introduction
O
R
O
OH
NH2
!-amino acid
R
NH2
R
N
H
O
OH
O
R
NH2
dipeptide
R
N
H
O
H
N
O
OH
R
tripeptide
  oligopeptide: 3 - 10 amino acids
  polypeptide, or protein: many amino acids
6
Proteins: Amino Acids, Configuration
NH2
HO
O
phenylalanine
O
C O+H N
H
3
R
same as -O C
2
NH3+
R
7
Classification of Amino Acids
•  Hydrophobic: water-fearing, nonpolar side
chains
–  Alkyl side chain
•  Hydrophilic: water-loving side chains
–  Polar, neutral side chains
–  Anionic
–  Cationic
8
Nonpolar
Side Chains
9
Polar,
Neutral
Side
Chains
10
Polar, Acidic Side Chains
11
Basic, Polar Side Chains
12
Amino acids: Zwitterions
  contain the amino group
  contain the carboxylic acid group:
NH3+
HO2C
R
NH2
HO2C
NH2
HO2C
NH3+
-O
2C
R
R
R
NH2
-O
2C
R
a zwitterion
pH = 0
pH = 7
pH = 11
13
Amino acids: Zwitterions
pKa of amino acids:
NH2
HO2C
R
NH2
HO2C
R
α-amino: 8.84 - 10.60
carboxylic acid: 1.82 - 2.63
14
Amino acids: Zwitterions
pKa of side-chains:
NH2 O
HO
H
NH2
OH
HO
O
OH
aspartic acid
glutamic acid
pKa 3.86
pKa 4.25
NH2
HO
HO
O
O
OH
O
tyrosine
pKa 10.07
O
H
cysteine
histidine
pKa 6.04
pKa 8.35
NH2
NH2
HO
NH3+
SH
HO
N+
HO
H
N
NH2
NH2+
O
O
O
NH2
NH2 N
lysine
arginine
pKa 10.79
pKa 12.48
15
Amino acids: Zwitterions
16
Amino acids: Zwitterions
PROBLEM 8
Draw the predominant form of glutamic acid in a solution with the
following pH:
9.67
a.  0
NH2
OH 4.25
2.19 HO
b.  3
c. 
O
O
glutamic acid
6
d.  11
17
Amino acids: Isoelectric Point (pI)
pI of amino acid is pH at which it has no net charge
18
Amino acids: Isoelectric Point (pI)
pI of amino acid is pH at which it has no net charge
1.82
9.17 H
NH3+ N
HO
N+
O
6.04
H
similarly ionizing groups
19
Amino acids: Separation/Purification
  electrophoresis
based on pI values of amino acids
O
OH
visualized with ninhydrin:
OH
O
buffer
paper or gel
20
arginine, alanine, and aspartate separated at pH = 5
Amino acids: Separation/Purification
  paper/thin layer chromatography
based on polarity
O
OH
visualized with ninhydrin:
OH
O
21
glutamate, alanine, and leucine
Amino acids: Separation/Purification
  ion-exchange chromatography
based on ions/charge
used on preparative scale
washed with buffers
of increasing pH
packed with insoluble
resin beads
22
Amino acids: Separation/Purification
  ion-exchange chromatography
A typical chromatogram obtained from separation of
amino acids using an automated analyzer
23
Ion-exchange chromatography can be used to perform
preparative separation of amino acids:
Negatively charged resin binds selectively to
positively charged amino acids
24
Amino acid synthesis: HVZ reaction
Hell-Volhardt-Zelinski reaction, see Section 18.5
1. Br 2, PBr 3
2. H 2O
O
R
O
R
OH
excess NH 3
OH
Br
O
R
OH
+ NH 4Br
NH 3+
25
Amino acid synthesis: reductive amination
review Section 17.10
1. excess NH 3
O
R
2. H 2, Pd/C
O
R
O-
OH
NH 3+
O
O
R
OH
NH
intermediate
26
Amino acid synthesis: N-phthalimidomalonic
O
O
O
EtO
OEt
O
N
K
EtO
Br
O
O
!-bromomalonic ester
H
O
EtO
OEt
N
O
potassium phthalimide
N-phthalimidomalonic ester
O
O
EtO
O
O
OEt
N
O
R Br
R
EtO
O
O
HCl, H 2O
OEt
N
O
heat
O
R
CO2H
OH
NH 3+
CO2
CO2H
phthalic acid
review Sections 18.18, 16.18, and 18.1
27
Amino acid synthesis: Strecker synthesis
NH 3
R
NaCN, HCl
R
R
!-amino nitrile
an imine
HCl, H 2O
heat
N
NH 3+
NH
O
C
O
R
OH
+
NH 4Cl
NH 3+
review Section 16.19 for nitrile hydrolysis
28