Lecture Eleven : Amino Acids, Peptides and Proteins Convener : Dr. Fawaz Aldabbagh First Year Organic Chemistry Biological Chemistry

All DNA encoded aa are  All are chiral, except Glycine R = H All DNA encoded aa are usually L-

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

aa are high melting point solids! Why? Answer = aa are ionic compounds under normal conditions 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 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 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

Cysteine residues create Disulfide Bridges between chains This does not reveal Primary Structure

Dr. Frederick Sanger, Nobel Prize for Chemistry 1958 and 1980 Peptide sequencing Prof. R. B. Merrifield Nobel Prize for Chemistry 1984 Automated 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 properties Bays or pockets in proteins are called Active Sites Enzymes 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 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