15- sar part 1 drug binding

Question 1

what are the 5 ways drugs produce effects by binding to biomolecules?

Answer 1

• enzyme inhibitor
• agonist
• antagonist
• modulator (ion channel agonist/antagonist)
• structural effects (protein association/dissociation)

Question 2

what are the 4 ways drugs bind to targets using non bonding interactions

Answer 2

• electrostatics
• H bonding
• dipole-dipole
• van der walls
  
  • dispersion forces

Question 3

what causes selectivity in the non bonding interactions

Answer 3

the pattern of it
if the non bonding interactions fit together and match, they can bind and molecule can stick to drug
if they do the same pattern (like h bonding) they can fit

Question 4

explain how drugs can bind covalently

Answer 4

Pattern of non-covalent interactions determines location of covalent bond
two functional groups- x and y can form a covalent bond
X and Y only covalently bond if the non bonding interactions allow the things to fit together in the first place

Question 5

what is the strongest type of interaction between two non bonding molecules? and what does it depend on?

Answer 5

electrostatic
Strength depends on surrounding environment
also depends on distance
it’s non directional

Question 6

explain the diagram with an exposed binding site vs lipophilic pocket

Answer 6

water has ability to interact with charges
negative charge won’t be able to interact with the + if H2O is in the way
solvent exposed=weak interactions
inside lipophilic pocket=strong interaction because the bio molecule is non polar inside and it’s a barrier

Question 7

what is the second strongest type of interaction between two non bonding molecules? what does it depend on?

Answer 7

H bonding
strong interaction
Strength depends on surrounding environment
Stronger in hydrophobic environments
depends on distance (closer=stronger)
becomes stronger in non polar environment

Question 8

explain directionality for H bonds

Answer 8

Strongest interaction when X-H bond points directly towards the axis of the lone pair of the acceptor

Question 9

what are some examples of H bond donors

Answer 9

X-H heteroatoms like:
OH’s, NH’s, NHR, CO2H, CONHR
C-F can act as a donor rarely

Question 10

what are some examples of H bond acceptors

Answer 10

provide lone pair to form hydrogen bond
N, O are good acceptors that have longe pairs
weak acceptors is S

Question 11

what is the third strongest type of interaction between two non bonding molecules? what does it depend on?

Answer 11

dipole dipole interactions
Moderate-strength interaction
Strength depends on surrounding environment
Stronger interaction in hydrophobic and nonpolar environments
distance again
Carbonyl groups

Question 12

what is the weakest type of interaction between two non bonding molecules? what does it depend on?

Answer 12

van der walls (dispersion forces)
Relatively weak
Strength depends on surface area -> more SA=stronger
Important in many binding pockets, like the non polar regions of the interior of binding pockets

Question 13

explain why lipophilicity can improve potency of drugs

Answer 13

De-solvation: going to be surrounded by H2O, and before two things can stick to each other, water must be removed 
Drug potency (binding) is an equilibrium between drug dissolved in water and drug “dissolved” in protein

Question 14

why is desolvation is important for drugs?

Answer 14

“Empty” binding pockets are actually full of water
These water molecules are stripped away as the drug enters the binding site (requires energy as polar drugs cling to water)
Binding pockets are often very lipophilic (so it facilitates water removal and ligand binding, spending less energy)
result: Drugs are often very lipophilic