Lecture Eleven : Amino Acids, Peptides and Proteins

Convener : Dr. Fawaz Aldabbagh

First Year Organic Chemistry

Biological Chemistry

CHO

H OH

CH2OH

CHO

HO H

CH2OH

D - L -

=

R

C CO2HH

H2N

(L) - Amino Acids(-) -

=

CHO

CH2OHH

HO

(S) - Glyceraldehyde(-) -

R

CHH2N CO2H

All DNA encoded aa are

All are chiral, except GlycineR = HAll DNA

encoded aa are usually L-

Of the 20 aa, only proline is not a primary aa

NH2

C

(H3C)2HC

H

NH2

C COOHHCH9(CH3)2

(S) -Enantiomer (R) -Enantiomer

Draw tetrahedral 3D structures for (R) and (S) valine

HOOC

O

OHR

NH2

O

OH

NH

Proline (Secondary aa)

aa are high melting point solids! Why?

Answer = aa are ionic compounds under normal conditions

C

O

OHR

NH3

C

O

OR

NH3

C

O

OR

NH2

LOW pH

Zwitterion

NEUTRAL

Carboxylate Form

HIGH pH

ammonium Form

Isoelectric Point = concentration of zwitterion is at a maximum and the concentration of cations and anions is equal

For 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

NC R

R'

O

NC R

R'

O

Features of a Peptide Bond;1. Usually inert2. Planar to allow delocalisation3. Restricted Rotation about the amide bond4. 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

Strong Acid Required to hydrolyse peptide bonds

CH3

H3N CO

O

CH

H3N CO

O

CH2OH

H3N CO

O

Alanine SerineValine

CH3

H3N C

HN

O CH2OH

CNH

O

CO

O

Tripeptide : Ala . Ser. Val

- 2 H2O

(CH2)4NH2

H2N C

HN

O

S

CNH

O

C

Ph

OH

O

S

CNH

O

OHC

O

HN

HOO

H2N

Ph

Lys. Cys. Phe

Phe. Ser. Cys

1. RSH

2. 6 M HCl hydrolysis

Lys + 2 Cys + 2 Phe + Ser

Cysteine residues create Disulfide Bridges between chains

This does not reveal Primary Structure

RS H RS SROxidation

Reduction

REVERSIBLE DENATURING

Dr. Frederick Sanger, Nobel Prize for Chemistry1958 and 1980Peptide sequencing

                               

Prof. R. B. MerrifieldNobel Prize for Chemistry 1984Automated Peptide Synthesis

                               

Prof. Linus Pauling

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 propertiesBays or pockets in proteins are called Active SitesEnzymes are Stereospecific and possess Geometric Specificity

Emil Fischer formulated the lock-and-key mechanism for enzymes

The range of compounds that an enzyme excepts varies from a particular functional group to a

specific compound

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