Drug-Receptor Bonding

Question 1

Importance of intermolecular forces in drug-receptor bonding.

Answer 1

• They act between and within molecules to hold a 3D shape
• They stabilise the receptor shape in water
• They determine how the receptor and molecule interact
• Knowledge about the forces gives us an insight into how to improve molecule and formulation.

Question 2

What type of molecule is a receptor?

Answer 2

A protein

Question 3

Types of non-covalent bonding/interactions:

Answer 3

1. Hydrogen bonds
2. Salt bridge/ionic
3. Packing (Van der Waals)

Question 4

What is Wallace’s Rule used for?

How is it determined?

Answer 4

Used to predict the temperature at which DNA separates into strands based on base sequence.

Determined using a formula which considers numbers of base pairings.

AT = 2 hydrogen bonds - 2 degrees

GC = 3 hydrogen bonds - 4 degrees (harder to break)

Question 5

How does hydrogen bonding happen in drug-receptor interactions?

Answer 5

Some drug molecules contain H bond donor/acceptor groups

Question 6

How do ionic interactions occur in drug-receptor bonding?

Answer 6

Some drugs have an acidic group which can be ionised to an anion.

Some have basic groups which can be ionised to a cation.

Some drugs are permanently charged.

Interaction is purely electrostatic.

Question 7

How do VDW forces work?

How do they work in aromatic rings?

Answer 7

They are the weaker form of interaction in which molecules pack closely together to minimise the empty space/maximise contact.

“pi-pi” stacking - seen in amino acids, nucleic acids and many ligands. Bigger rings have greater interaction.

Induced fit as ligand binds.

Question 8

Link to water in drug-receptor binding?

Answer 8

Many amino acids/ligand groups are lipophilic/hydrophobic. Depending on how hydrophobic will determine equilibrium between organic/aqueous phases.

Question 9

Effect of water on non-polar (hydrophobic) molecules.

Answer 9

On binding, ligand and receptor lose unfavourable interaction with water.

Improved enthalpy and entropy.

Question 10

Effect of water on polar (hydrophilic) molecules.

Answer 10

On binding, ligand and receptor lose some favourable interaction with water.

Large amount of energy required to break these interactions.

Question 11

Covalent bonding in drug/receptor interactions.

Examples of where this might be seen in medicine.

Answer 11

Very strong so rarely seen in medicine (would lead to prolonged or irreversible effect)

Sometimes this is desirable e.g. anti-bacterial, insecticides and anti-cancer

e.g. penicillin