Transcript Peptide Bonds

Biological Chemistry
First Year Organic Chemistry
Lecture Eleven :
Amino Acids, Peptides and Proteins
Convener : Dr. Fawaz Aldabbagh
R
H2N
CH
CO2H
All DNA encoded aa are 
CHO
All are chiral,
except Glycine
R=H
H
OH
CHO
HO
CH2OH
CH2OH
D-
All DNA
encoded aa
are usually L-
H
LR
CHO
=
HO
CH2OH
H
(S) - Glyceraldehyde
(-) -
=
H2N
C
CO2H
H
(L) - Amino Acids
(-) -
Draw tetrahedral 3D structures for (R) and (S) valine
NH2
NH2
C
HOOC
(H 3C) 2HC
H
H
C
COOH
CH9(CH 3)2
(R) -Enantiomer
(S) -Enantiomer
Of the 20 aa, only proline is not a primary aa
O
O
R
OH
NH2
OH
N
H
Proline (Secondary aa)
aa are high melting point solids! Why?
Answer = aa are ionic compounds under normal conditions
LOW pH
NEUTRAL
C
O
O
O
R
HIGH pH
R
C
OH
NH3
ammonium Form
R
C
O
NH3
Zwitterion
O
NH2
Carboxylate Form
Isoelectric Point = concentration of zwitterion is at a
maximum and the concentration of cations and anions is equal
r aa with basic R-groups, we require higher pHs, and
for aa with acidic R-groups, we require lower pHs
to reach the Isoelectric Point
aa are covalently linked by amide bonds
(Peptide Bonds)
The resulting molecules are called
Peptides & Proteins
R'
R'
N
C
O
R
N
C
R
O
Features of a Peptide Bond;
1. Usually inert
2. Planar to allow delocalisation
3. Restricted Rotation about the amide bond
4. Rotation of Groups (R and R’) attached to the amide
bond is relatively free
aa that are part of a peptide or protein are referred
to as residues.
Peptides are made up of about 50 residues, and do not
possess a well-defined 3D-structure
Proteins are larger molecules that usually contain at least 50
residues, and sometimes 1000. The most important feature of
proteins is that they possess well-defined 3D-structure.
Primary Structure is the order (or sequence) of amino acid residues
Peptides are always written and named
with the amino terminus on the left and
the carboxy terminus on the right
CH2OH
CH3
O
O
H3N
CH
H3 N
C
O
C
H3N
C
O
O
O
Serine
Alanine
Valine
- 2 H2O
CH3
O
H
N
H3N
C
C
O
CH2OH
O
N
H
C
O
Tripeptide : Ala . Ser. Val
Strong Acid Required to hydrolyse peptide bonds
Lys. Cys. Phe
Phe. Ser. Cys
1. RSH
2. 6 M HCl hydrolysis
Lys + 2 Cys
+ 2 Phe + Ser
Ph
Cysteine residues create
Disulfide Bridges
between chains
(CH2)4NH2
O
H
N
H2 N
C
C
OH
N
H
O
O
This does not reveal
Primary Structure
S
S
Ph
O
H
N
H2 N
C
OH
N
H
O
C
O
HO
C
REVERSIBLE DENATURING
Oxidation
RS SR
RS H
Reduction
Prof. Linus Pauling
Dr. Frederick Sanger,
Prof. R. B. Merrifield
Nobel Prize for Chemistry Nobel Prize for Chemistry 1984
1958 and 1980
Automated Peptide Synthesis
Peptide sequencing
Secondary Structure
The Development of Regular patterns of Hydrogen
Bonding, which result in distinct folding patterns
-helix
-pleated sheets
Tertiary Structure
This is the 3D structure resulting from further regular
folding of the polypeptide chains using H-bonding, Van
der Waals, disulfide bonds and electrostatic forces –
Often detected by X-ray crystallographic methods
Globular Proteins – “Spherical Shape” , include Insulin,
Hemoglobin, Enzymes, Antibodies
---polar hydrophilic groups are aimed outwards towards water,
whereas non-polar “greasy” hydrophobic hydrocarbon portions
cluster inside the molecule, so protecting them from the hostile
aqueous environment ----- Soluble Proteins
Fibrous Proteins – “Long thin fibres” , include Hair,
wool, skin, nails – less folded ----- e.g. keratin - the -helix strands
are wound into a “superhelix”. The superhelix makes one
complete turn for each 35 turns of the -helix.
In globular proteins this tertiary structure or
macromolecular shape determines biological properties
Bays or pockets in proteins are called Active Sites
Enzymes are Stereospecific and possess Geometric Specificity
The range of compounds that an enzyme excepts varies
from a particular functional group to a specific compound
Emil Fischer formulated the lock-and-key mechanism for enzymes
All reactions which occur in living cells are mediated by enzymes and
are catalysed by 106-108
Some enzymes may require the presence of a Cofactor.
This may be a metal atom, which is essential for its redox activity.
Others may require the presence of an organic molecule, such as
NAD+, called a Coenzyme.
If the Cofactor is permanently bound to the enzyme, it is called a
Prosthetic Group.
For a protein composed of a single polypeptide molecule, tertiary
structure is the highest level of structure that is attained
Myoglobin and hemoglobin were the first proteins to be
successfully subjected to completely successful X-rays
analysis by J. C. Kendrew and Max Perutz (Nobel Prize for
Chemistry 1962)
Quaternary Structure
When multiple sub-units are held together in
aggregates by Van der Waals and electrostatic
forces (not covalent bonds)
Hemoglobin is tetrameric myglobin
For example, Hemoglobin has four heme units, the protein
globin surrounds the heme – Takes the shape of a giant
tetrahedron – Two identical  and  globins.
The  and  chains are very similar but distinguishable in both
primary structure and folding