PHRM 824: Lecture 5

Question 1

drugs often bind to their targets at ____ concentrations

Answer 1

low

Question 2

what is a pharmacophore?

Answer 2

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

Question 3

4 types of binding forces

Answer 3

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

Question 4

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

Answer 4

covalent bond

Question 5

energy for covalent bond is

Answer 5

50 to 150 kcal/mol

Question 6

energy used for this is considered to be high

Answer 6

covalent bond

Question 7

covalent bonds are generally ______ rather than ______

Answer 7

electrophilic

nucleophilic

Question 8

electrostatic interactions involve?

Answer 8

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

Question 9

these are very strong attractive forces, operate over long distances

Answer 9

ion-ion or charge-charge interaction

Question 10

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

Answer 10

5-10 kcal/mol

Question 11

this is a charged species like solvation

Answer 11

ion-dipole

Question 12

hydrogen bond is considered in which of the 4 groups

Answer 12

electrostatics

Question 13

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

Answer 13

hydrogen bond

Question 14

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

Answer 14

not as strong

about 1/10th as strong

Question 15

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

Answer 15

hydrophobic interactions

Question 16

this is a type of hydrophobic interactions

Answer 16

van der waals forces

Question 17

the energy of van der waals forces is what

Answer 17

0.5-1 kcal/mol

Question 18

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

Answer 18

• bonds
• increase, entropy
• water molecules
• non-polar

Question 19

this type of binding includes a charge transfer

Answer 19

aromatic ring interactions

Question 20

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

Answer 20

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

Question 21

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

Answer 21

• electron-rich

- electron-deficient

Question 22

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?

Answer 22

• pi

- pi stacking

Question 23

in aromatic ring interactions instead of dipole moments they have?

Answer 23

quadripole moments

Question 24

aromatic ring interactions have two types

Answer 24

1) charge transfer

2) cation-pi

Question 25

aromatic ring interactions: cation-pi a lot of cations bind to the receptor or enzyme by being sequestered around ___ ____ ____ ____

Answer 25

- aromatic rich amino acids

Question 26

aromatic ring interactions: cation-pi some of these positively charged amines can be?

Answer 26

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

Question 27

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

Answer 27

aromatic ring interactions: Cation-pi

Question 28

and example of this cation- pi is?

Answer 28

acetylcholine binding to tryptophan

Question 29

what drug receptor example did we use?

Answer 29

beta-2-adrenergic receptor and isoproterenol

Question 30

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

Answer 30

TRUE

Question 31

when we think of steric properties we think of

Answer 31

steric clash

Question 32

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

Answer 32

bulky

Question 33

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

Answer 33

- fill the pocket - tropic - water

Question 34

most drugs interact with their protein targets

Answer 34

non-covalently

Question 35

this is the rate constant for association of the complex

Answer 35

ka

Question 36

this is the rate constant for dissociation of the complex

Answer 36

kd

Question 37

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

Answer 37

- association constant, ka

Question 38

the higher the ka value?

Answer 38

the more favorable - higher affinity binding

Question 39

the smaller the kd?

Answer 39

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

Question 40

binding energies typically range from ______ kcal/mol

Answer 40

6-15

Question 41

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

Answer 41

- negative | - Ka > Kd

Question 42

the more negative the delta G the?

Answer 42

great the affinity

Question 43

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

Answer 43

adopt the necessary conformation to activate the target receptor

Question 44

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

Answer 44

inactive receptor state

Question 45

what happens really in indirect steric effects?

Answer 45

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

Question 46

this is the concentration of drug that gives half maximal activity

Answer 46

EC50

Question 47

what is an example of us looking at EC50?

Answer 47

- kill cancer, so effective concentration of durg at which you killed 1/2 of your cancer cells

Question 48

concentration of drug that vies half-maximal receptor binding

Answer 48

Kd

Question 49

basically Kd is telling us

Answer 49

receptor is 1/2 drug bound