EXAM 1 - Properties of Drug: Target Interactions

Question 1

what is Kon and Koff?

Answer 1

Kon - the rate that the ligand and receptor bind to eachother
Koff - the rate that the ligand and receptor dissociate from eachother

Question 2

Kd = ______

Answer 2

Kd = [receptor][ligand]/[receptor:ligand]
Kd tells you the binding affinity situation at equilibrium

Question 3

as Kd becomes smaller, what happens to the receptor:ligand complex?

Answer 3

it increases

Question 4

what is deltaG?

Answer 4

energy needed to bind
- total energy used or produced by binding event
- pos is endothermic/non-spontaneous
- neg is exothermic/spontaneous

Question 5

What is deltaH?

Answer 5

enthalpy
E(break) - E(form)
- neg is more favorable

Question 6

What is deltaS?

Answer 6

entropy - disorder
- loss of conformational freedom
- neg is unfavorable

Question 7

characteristics of non-covalent interactions

Answer 7

• no electron sharing
• weak interactions between molecules
• exothermic reactions
• stabilize receptor:ligand complex

Question 8

Describe ionic bonds

Answer 8

• strongest intermolecualr bond
• opposite charge attraction
• stronger interactions occur in hydrophobic envrionments

Question 9

describe hydrogen bonds

Answer 9

• weaker than ionic but stronger than VDWs
• between electron deficient hydrogen and electron rich N or O

Question 10

Describe van der Waals interactions

Answer 10

• the weakest interaction
• occurs between hydrophobic regions of the drug and target
• transient areas of high and low electron densities cause temporary dipoles –> binding
• must be close together

Question 11

types of pi-pi interactions

Answer 11

benzenes stacked
benzenes displaced stacked
t-shape
- occurs when two aromatic systems are co-planar
- seen inserted into DNA

Question 12

describe ion-dipole interactions

Answer 12

charge on one molecule interacts with dipole moment of another molecule
- stronger than dipole-dipole

Question 13

describe induce-dipole interactions

Answer 13

• charge on one molecule induces a dipole on another molecule
• between quaternary ammonium ion and an aromatic ring

Question 14

what type of bonding/interaction occurs in a pi-pi interaction?
a) hydrogen bonding
b) dipole-dipole interactions
c) van der Waals
d) ionic/electrostatic

Answer 14

c) van der Waals

Question 15

Why is desolvation necessary?

Answer 15

• desolvation must occur before interaction between drug and target
• desolvation requires energy to remove water molecules
• the drug must have a higher affinity to the target than the solvent (water) for it to bind

Question 16

how do polar groups affect desolvation?

Answer 16

polar groups on both the target and the drug increase hydrophilicity
- makes it harder to remove the water

Question 17

How are hydrophobic interactions contribute to entropy?

Answer 17

• water molecules form an ordered layer around the hydrophobic membrane of the drug (negative entropy)
• when the drug binds to the target, the water molecules are ‘freed’
• increases entropy
• beneficial to binding energy

Question 18

`Are covalent bonds used in drugs? why or why not?

Answer 18

covalent bonds are avoided because they are highly reactive, are less specific, and have permanent binding
- nucleophile on target and electrophile on drug

Question 19

Steps of the composite binding model

Answer 19

1) solvated ligand must achieve bioactive conformation (the formation that properly presents the pharmacophore to the receptor)
2) solvated ligand removes water of solvation
3) ligand binds to site, providing free energy from interactions (increase entropy)
4) ligand dissociates from binding site