Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHAR 503 > 1. Drug-Target Interactions > Flashcards

1. Drug-Target Interactions Flashcards

1
Q

what is a target?

A

any cellular macromolecule that a drug binds to –> enzyme, receptor, protein, or DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is a drug?

A

chemical substance that interacts with target to produce beneficial physiological effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what mediates the ability of a drug to bind its receptor?

A

drug chemical structure interacts with complementary surfaces on the target to elicit intermolecular forces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is the difference between a drug and chemical?

A

both bind at target but drug produces biologically beneficial effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is a binding pocket?

A

3D structure within the target in which the drug fits and binds (i.e. AA that the drug interacts with)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is a pharmacophore?

A

the drug’s steric (shape and position) and electronic features (chemical functional groups) that are necessary to ensure the interactions with target trigger/block a biologic response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

ENZYMES vs RECEPTOR

A
  • Enzyme has catalytic active site where reaction occurs
  • Receptor has ligand binding site
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are the 3 models of drug-target binding? which are possible?

A
  1. lock and key
  2. induced fit
  3. conformational selection/selected fit

2 and 3 are possible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

describe the lock and key

A

less accurate now –> perfect match between drug and target

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

describe the induced fit model

A

drug approximates target, then when drug is present, the target changes conformation to allow binding
- favoured by entropy
- ex. Gleevec

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

describe the conformational selection/selected fit model

A

target is constantly changing conformation (due to enzymes or random thermal motion) and only at specific conformation will the drug bind

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is affinity?

A

measure of the TIGHTNESS with which a drug binds to the receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what does affinity depend on?

A

quality and number of intermolecular forces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

besides affinity, what 2 other factors influence binding?

A
  1. water shell
  2. pH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

describe covalent bonds and their energy

A

no affinity involved –> they are 1 molecule, there is no dissociation constant

highest energy!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

describe ionic interactions and their length

A

not very specific –> just cation-anion attraction

pretty long bonds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is an example of ionic interaction?

A

C-terminus binding N-terminus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

describe H bonds and their length

A

Electron-deficient hydrogen is covalently bonded to an electronegative atom (O, N, F) and then binds electron-rich heteroatom

longer bond so less energy –> easier to break the bond

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is a hydrogen bond donor? what is a hydrogen bond acceptor?

A

donor: H covalently bonded to O, N, F

acceptor: electron-rich atom on a functional group

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

describe why hydrogen bond donors form

A

hydrogen is covalently bonded to an electronegative atom which has a greater attraction for electrons, so the electron distribution in the bond gives H a slight positive charge

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what are some examples of hydrogen bond acceptor?

A

C=O, C=N-C, C-O-C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what is an example of hydrogen bond donor?

A

OH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what is an example of a hydrogen bond donor and acceptor?

A

NH3 –> can act as either donor or acceptor in different cases

24
Q

when do we see hydrogen bonds in biomolecules?

A
  1. water shell –> btwn OH or C=O and water
  2. secondary protein structure –> btwn peptide groups in polypeptides
  3. DNA base pairing
25
Q

what are some examples of amino acids that are hydrogen bond acceptors only?

A

glutamic/aspartic acid

26
Q

what are some examples of amino acids that are hydrogen bond donors and acceptors?

A
  • serine
  • threonine
  • glutamin asparagine
  • histidine
  • tyrosine
27
Q

what are some examples of amino acids that are hydrogen bond donors?

A
  • lysine
  • arginine
  • tryptophan
28
Q

describe van der Waals interactions

A

less specific –> just hydrophobic interactions

due to distortions in electron clouds

29
Q

why can we not determine affinity?

A

cannot determine van der Waals forces

30
Q

describe dipole dipole interactions and their strength

A

due to permanent or induced dipoles from electronegativity –> can be induced

stronger than van der Waals but drug and target must be very close to each other!

31
Q

what is an example of a part of a molecule with a permanent dipole?

A

ketone

32
Q

describe pi-pi bonding

A

amino acid side chains with an aromatic ring interact with each other

due to 3 pairs of delocalized/unpaired electrons with transient delta positive charge interacting with transient delta negative charge

33
Q

what are 4 amino acids that can undergo pi pi bonding?

A
  1. tryptophan
  2. phenylalanine
  3. histidine
  4. tyrosine
34
Q

what is the water shell? how do we have drug-target interactions in the presence of the water shell?

A

water is everywhere –> at binding site, covering drug

must remove water for interaction to be stabilized –> this requires energy

35
Q

when could a drug be ineffective in relation to the water shell?

A

if the energy required to remove the energy is greater than the stabilization energy, the drug may be ineffective

36
Q

what is structured water?

A

water binds hydrophilic parts and forms strong H bonds at hydrophobic parts –> decreases entropy

37
Q

how is structured water overcome? what does this result in?

A

when the hydrophobic region of a drug interacts with the hydrophobic region of the binding site, the structured water is overcome –> leads to increase in entropy and binding energy which is more favoured –> thermodynamic drive to have drug and target interact

38
Q

how does water play a role in affinity?

A

once water shell is overcome –> water plays no role in affinity

39
Q

how does adding polar groups to a drug affect its binding?

A

water solubility increases but must be solvent-accessible by having a part that protrudes from the binding site so water doesn’t have to be stripped away

40
Q

how is affinity measured? what does this mean?

A

as Kd (in M)

concentration of drug required to bind 50% of receptors

41
Q

small Kd = ____ affinity

A

small Kd = high affinity

42
Q

what are the 3 units of M where drug affinity usually is?

A
  • microM (10^-6)
  • nanoM (10^-9)
  • picoM (10^-12)
43
Q

how does the equilibrium shift of [R]+[L]<=>[RL] when there are more intermolecular forces?

A

shift to the right

44
Q

describe the core of an amino acid

A

ZWITTER ION at neutral pH –> ammonium ion and carboxylate ion –> separate positive and negative charged groups

45
Q

what are some aliphatic amino acids? are they polar or nonpolar? where are these amino acids commonly found in cells?

A
  • glycine
  • alanine
  • proline
  • valine
  • leucine
  • isoleucine
  • methionine

NONPOLAR –> all C and H

nonpolar so good for hydrophobic environment of membrane

46
Q

what are some aromatic amino acids? which are polar, which are non-polar?

A
  • phenylalanine (non-polar)
  • tyrosine (polar)
  • tryptophan (non-polar)
47
Q

what is special about tryptophan?

A

super energy consuming to produce, so usually has specific important role

if just need a hydrophobic aromatic amino acid, use phenylalanine

48
Q

what are some polar amino acids? what kind of interactions do they have?

A
  • serine
  • threonine
  • aspargine
  • cysteine
  • glutamine

since they are polar –> they have dipoles and can have dipole-dipole interactions

49
Q

what are some positively charged amino acids? what kind of interactions do they have? are they in transmembrane sequences?

A
  • lysine
  • arginine
  • histidine

ionic interactions

usually not in transmembrane sequences - except lysine in EGF receptor HER2

50
Q

what are some negatively charged amino acids?

A
  • aspartate
  • glutamate
51
Q

describe a peptide bond
- how it is formed
- its electrons
- orientation
- H donor or acceptor?

A
  • ribosome causes condensation reaction to cleave out water and join N-terminal with C-terminal
  • electron rich –> electrons float around, resonance stabilized
  • planar –> restricts mobility of protein to allow proper folding
  • H donor AND acceptor
52
Q

how is the 3D structure of protein stabilized?

A

intramolecular forces that make up secondary structures

53
Q

why is the movement of things in water different from cytosol?

A

in cytosol, there are proteins and other things that have intermolecular forces that affect the movement

54
Q

in secondary structures, what do ionic interactions produce?

A

salt bridge

55
Q

why are DISULFIDE bridges important?

A

important for protein folding to make sure distant regions of a protein can interact

56
Q

why can it be hard for drugs to cross the membrane?

A

many proteins in the membrane and other things to impede movement

57
Q

what are 2 ways we can increase a drug’s effectiveness?

A

change its interactions so its easier to reach target
1. ex. more hydrophobic so its easier to get thru water in cytosol
2. ex. increased interaction in binding pocket to increase affinity and increase effect

PHAR 503 (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions