Lecture 1 - Structures of Proteins

Question 1

What are the 4 components of cells that are targets for drugs?

Answer 1

• Lipids
• Carbohydrates
• Proteins
• Nucleic acids

Question 2

Amide structure

Answer 2

• Chemically inert due to lone pair on N delocalising into carbonyl group
• Planar so high energy barrier to rotation about C-N bond
• Secondary amides adopt transoid conformation (double bonds antiperiplanar) as a result of steric repulsion

Question 3

Features of the two types of secondary structure of proteins (alpha helix and beta pleated sheet)

Answer 3

• Alpha helix: results from coiling of peptide chain. Held together by H bonds. Amino acid residues stick out at right angles to minimise steric interactions.
• Beta pleated sheet: Layering of peptide chains on top of each other. Held together by H-bonds. Amino acid residues at right angles to the sheets.

Question 4

Bonds involved in maintaining tertiary strcuture of proteins, energy involved (kJ/mol) and an example

Answer 4

• Covalent: Less important, 250-350, e.g. disulfide bridge (Cys-Cys)
• Ionic: Only available for 4 of 20 naturally occuring amino acids, 20-25, -C—N+ (Asp-Lys)
• Hydrogen: Available for 8 amino acids, 7-40, O—-H (Ser-Ser)
• Van der Waals: Available for 8 amino acids, 1.9, Ph—-Ph

Question 5

What is the difference between dipole-dipole interactions and ion-dipole interactions?

Answer 5

• Dipole-dipole: when the dipole in a particular functional group is attracted to dipole in the protein structure of the active site
• Ion-dipole: where the dipole interactions with a charged ion

Question 6

Equation for reaction between drug and receptor

Answer 6

Drug + receptor <—> Complex
Forward reaction rate constant = Kf
Reverse reaction rate constant = Kr
Delta G = -RTlnK
Delta G = delta H (standard) - T x delta S
K must be determined experimentally to calculate delta G

Question 7

Examples of drugs/transmitters, their target/use and the bonds involved (4 examples)

Answer 7

• Acetylcholine (transmitter): Targets muscarinic/nicotinic receptors (these pathways involved in cholinergic transmission), H-bonds, ionic, hydrophobic
• Cyclopentolate (antagonist drug): Muscarinic receptor antagonist(antagonist that works against ACh/ophthalmic inspection for pupil dilution to inspect eyes at opticians), H-bond, ionic, hydrophobic. Competitive inhibitor.
• Methotrexate (anticancer drug): targets enzyme dihydrofolate reductase/cancer chemotherapy, treats leukemia, derivatives treat malaria), Ionic, folate is important cofactor for DNA synthesis
• Dyflos (nerve agent): Acetyl cholinesterase enzyme inhibitor (target enzyme acetylcholineesterase/treats glaucoma/used in chemical warfare), covalent