1. CHM 708: MEDICINAL CHEMISTRY
Proteins

2. a-Amino-acids: Building blocks of proteins
Proteins are made up of 20 major amino- acids with different side chains

8. Peptide bonds

9. Primary Structure
A protein consists of a long chain (50 or more) or polymer of a-amino-acids, linked together by peptide (amide) bonds.
Short chains are called peptides.
The free NH3+ end is called the N-terminus, and the free CO2- end the C terminus.
The primary structure of a protein is the sequence of amino-acids in the chain.
The sequence of -N–C–C- segments in the chain is called the backbone.

10. Secondary Structure
This refers to the local spatial arrangement of the backbone atoms of segments of the protein chain.
Three main types:
a-Helix
b-Sheet
Irregular coils.
All are stabilised by H-bonding between backbone NH and C=O groups.

11. a-Helix

12. b-Strand (anti-parallel)

13. b-Strand (parallel)

14. b-Sheet

15. Tertiary structure
This is the overall arrangement of all the atoms in the protein, i.e., its overall shape.
Every protein has a natural tertiary structure – most stable shape. It is active only in that shape.
Tertiary structure is determined by primary structure.
Tertiary structure is stabilised by H-bonds, ionic bonds, polar interactions, hydrophobic interactions, dispersion (Van der Waals) forces, and certain types of covalent bonds.

16. Tertiary structures
Fatty-acid binding protein
Myoglobin

17. Multi-subunit Proteins
Some complex proteins consist of two or more amino-acid chains.
Each chain is called a subunit and has its own tertiary structure.
The arrangement of subunits in the overall protein is called the quaternary structure.
Quaternary structure is stabilised by the same forces as tertiary structure. So is the binding of small molecules to specific sites on the surface of the protein.

18. Quaternary structure
Yellow: a subunits
Red: b subunits
Haemoglobin

19. Functions of proteins Structural proteins (skin, hair, nails, etc.)
Muscle proteins (able to contract, use energy to do work).
Transport proteins.
Cell membrane proteins.
Membrane channels and pores
Molecular recognition and signalling.
Enzymes: catalysts of biological reactions.
Membrane-bound
Intra-cellular
Extra-cellular.

20. Protein-ligand binding
Most proteins function by, or as a result of, reversibly binding a small molecule (ligand).
Each ligand has a specific binding site (active site), into which it fits.
The binding of a particular ligand to a protein can be modulated by other ligands binding to the same protein.
Drug molecules binding to the protein at the active site or other sites can interfere with its normal functioning.