PHRM 824: Lecture 5 Flashcards Preview

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Flashcards in PHRM 824: Lecture 5 Deck (49)
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1
Q

drugs often bind to their targets at ____ concentrations

A

low

2
Q

what is a pharmacophore?

A

core part of a drug molecule that is interacting with the receptor active site and induce a biological response

3
Q

4 types of binding forces

A

1) covalent bond
2) electrostatics
3) hydrophobic interactions
4) aromatic ring interactions

4
Q

drugs of this type involve irreversible target modification and thus biological actions of long duration

A

covalent bond

5
Q

energy for covalent bond is

A

50 to 150 kcal/mol

6
Q

energy used for this is considered to be high

A

covalent bond

7
Q

covalent bonds are generally ______ rather than ______

A

electrophilic

nucleophilic

8
Q

electrostatic interactions involve?

A

1) ion-ion or charge-charge interactions
2) ion-dipole
3) dipole-dipole

9
Q

these are very strong attractive forces, operate over long distances

A

ion-ion or charge-charge interaction

10
Q

what is the kcal/mol for ion-ion or charge-charge interactions?

A

5-10 kcal/mol

11
Q

this is a charged species like solvation

A

ion-dipole

12
Q

hydrogen bond is considered in which of the 4 groups

A

electrostatics

13
Q

this is a particularly strong dipole-dipole interaction between a hydrogen atom and an electronegative atom (O,N,F)

A

hydrogen bond

14
Q

are hydrogen bonds stronger than ion-ion, ion-dipole, or dipole-dipole interactions?

A

not as strong

about 1/10th as strong

15
Q

this is an interaction between non-polar regions of drug and receptor

A

hydrophobic interactions

16
Q

this is a type of hydrophobic interactions

A

van der waals forces

17
Q

the energy of van der waals forces is what

A

0.5-1 kcal/mol

18
Q

in van der waals reactions, they don’t involve _____ per se; rather their driving force is an ____ in _____ resulting from the release of ___ ___ molecules initially bound to the ____ ____ surfaces

A
  • bonds
  • increase, entropy
  • water molecules
  • non-polar
19
Q

this type of binding includes a charge transfer

A

aromatic ring interactions

20
Q

in aromatic ring interactions wham charat happens in a charge transfer?

A
  • two aromatic rings interact cloesely, resulting in a small electron ‘flow’ between them
21
Q

aromatic ring interactions: typically occurs between ___ ___ and ___ ___ aromatic rigns

A
  • electron-rich

- electron-deficient

22
Q

aromatic rings can often interact favorably when they are put close together. You can get some degree of electron sharing between the ____ electrons. We call this?

A
  • pi

- pi stacking

23
Q

in aromatic ring interactions instead of dipole moments they have?

A

quadripole moments

24
Q

aromatic ring interactions have two types

A

1) charge transfer

2) cation-pi

25
Q

aromatic ring interactions: cation-pi

a lot of cations bind to the receptor or enzyme by being sequestered around ___ ____ ____ ____

A
  • aromatic rich amino acids
26
Q

aromatic ring interactions: cation-pi

some of these positively charged amines can be?

A

surrounded on almost all sided by 4 aromatic groups to stabilize that

27
Q

in this reaction, the electron rich pi system cloud neutralizes the charge of the cation - primarily electrostatic

A

aromatic ring interactions: Cation-pi

28
Q

and example of this cation- pi is?

A

acetylcholine binding to tryptophan

29
Q

what drug receptor example did we use?

A

beta-2-adrenergic receptor and isoproterenol

30
Q

every drug uses more than 1 way to bind to its target TRUE or FALSE

A

TRUE

31
Q

when we think of steric properties we think of

A

steric clash

32
Q

steric effects can arise from the presence of ____ groups on a drug molecule

A

bulky

33
Q

steric properties: often works that you want to _____ the ______ and usually represented by ____ effects of releasing ___ that might be taking up space

A
  • fill the pocket
  • tropic
  • water
34
Q

most drugs interact with their protein targets

A

non-covalently

35
Q

this is the rate constant for association of the complex

A

ka

36
Q

this is the rate constant for dissociation of the complex

A

kd

37
Q

the equilibrium ____ _____ ( ) is generally considered synonymous with the term affinity

A
  • association constant, ka
38
Q

the higher the ka value?

A

the more favorable - higher affinity binding

39
Q

the smaller the kd?

A

the more tightly it is bound = increased affinity and less likely to dissociate

40
Q

binding energies typically range from ______ kcal/mol

A

6-15

41
Q

free energy values are _____ if the association between drug and receptor is favorable AKA ta

A
  • negative

- Ka > Kd

42
Q

the more negative the delta G the?

A

great the affinity

43
Q

indirect steric effects: a molecule with a 2D structure similar to that of an active drug may be inactive if it cannot?

A

adopt the necessary conformation to activate the target receptor

44
Q

indirect steric effects: if a molecule cannot adopt the necessary conformation to activate the target receptor it binds to an

A

inactive receptor state

45
Q

what happens really in indirect steric effects?

A

the molecule may be unable to adopt a key conformation because it has bulky groups that prevent rotation about one of its bonds

46
Q

this is the concentration of drug that gives half maximal activity

A

EC50

47
Q

what is an example of us looking at EC50?

A
  • kill cancer, so effective concentration of durg at which you killed 1/2 of your cancer cells
48
Q

concentration of drug that vies half-maximal receptor binding

A

Kd

49
Q

basically Kd is telling us

A

receptor is 1/2 drug bound