lecture 1🅱️

Question 1

list possible protein drug targets

Answer 1

• proteins
• receptors
• enzymes
• transport proteins
• structural proteins (tubulin)

Question 2

are drug targets large or small molecules

Answer 2

large molecules

aka macromolecules

Question 3

are drugs smaller or larger than their targets

Answer 3

they’re smaller

Question 4

how do drugs interact with their targets

Answer 4

they interact by binding to binding sites

Question 5

what is a binding site on a drug target

Answer 5

• a hydrophobic hollow // cleft on the surface of the macromolecule

macromolecule = target

Question 6

what type of bonding is involved when drugs bind to macromolecule binding sites

Answer 6

intermolecular bonds

aka bonds between molecules!!

Question 7

what equilibrium are most drugs a part of

Answer 7

equilibrium of either being bonded to a macromolecule or free

Question 8

importance of functional groups

Answer 8

they make up binding groups as they are involved in binding interactions

Question 9

what is a binding region

Answer 9

specific regions within the binding site that are involved in binding interactions

Question 10

when a binding interaction occurs what 2 things normally line up

Answer 10

binding regions on the target

binding groups on the drug

Question 11

when does a binding site change shape to accommodate the drug

Answer 11

during induced fit!!!

caused by bonding interactions

Question 12

what does the induced fit model cause

Answer 12

causes a change in the binding site shape

Question 13

what does the induced fit model alter

Answer 13

the shape of the macromolecule
the shape of the binding site

important pharmacological effect of the drug

Question 14

what is the strongest intermolecular bond force

Answer 14

ionic // electrostatic bond

Question 15

between what groups do ionic // electrostatic bonds form

Answer 15

between groups of opposite charge

Question 16

electrostatic bond force and distance relationship

Answer 16

inversely proportional

Question 17

where do stronger electrostatic bonds form

Answer 17

in hydrophobic environments

Question 18

as distance increases,; how fast does the bond force decrease by

Answer 18

not that much tbh

it decreases but much slower than other intermolecular forces

Question 19

what initial interaction is most important when a drug enters the binding site

Answer 19

ionic bonds!!

Question 20

do hydrogen bonds vary in strength

Answer 20

yes!!!

Question 21

order electrostatic, hydrogen and VDW interactions

Answer 21

electrostatic
hydrogen
VDW

Question 22

what atom bonds with H to form a H bond

Answer 22

N, O

Question 23

describe the heteroatom

Answer 23

electron rich

Question 24

describe the H in hydrogen bonding

Answer 24

e- deficient

Question 25

what is the e- deficient hydrogen bond called

Answer 25

hydrogen bond donor

Question 26

what is the electron rich heteroatom called in hydrogen bonding

Answer 26

hydrogen bond acceptor

Question 27

describe hydrogen bonding

Answer 27

H and an N or O
involved orbitals + is directional

XH bond points towards the Y to form a linear, 180 molecule

Question 28

strong hydrogen bond acceptors

Answer 28

carboxylate ion

phosphate ion

tertiary amine

Question 29

moderate hydrogen bond acceptor

Answer 29

carboxylic acid

amide

oxygen

ketone

ester

ether

alcohol

Question 30

poor hydrogen bond acceptors

Answer 30

fluorine
chlorine
aromatic amine
aromatic ring
sulfur

Question 31

describe VDW

Answer 31

very weak intermolecular interaction
occurs between HYDROPHOBIC REGIONS of the drug and target
can cause temporary dipoles and e- aren’t static

• get weaker with distance
• drug must be close for interactions to occur
• overall contribution is crucial to binding

Question 32

when can dipole dipole interactions occur

Answer 32

• when the binding site and drug have dipole moments
• when dipoles align with eachother as they get closer
• dipole alignment orientates the molecule in the binding site.

Question 33

what happens to the dipoles when the target and drug get closer

Answer 33

they align + orientates the molecule in the binding site

Question 34

is orientation of the molecule always a benefit in dipole alignment

Answer 34

nope!!

can be beneficial or detrimental depending on if the binding groups are positioned correctly or not

Question 35

does the strength of a dipole dipole interaction decrease with distance

Answer 35

yup!!!!
less quickly than VDW but more quickly than electrostatic forces//interactions

Question 36

describe a molecule moving towards a binding site using dipole dipole interactions

Answer 36

the molecule comes towards it normally

the dipoles of the targets binding site and the drug align (+-) and rotate the drug in order for this to occur.

this occurs as the dipole on the target binding site is localised!!

Question 37

what dipole interaction is stronger than a dipole dipole interaction

Answer 37

an ion dipole interaction

Question 38

when do ion dipole interactions occur

Answer 38

when the charge on one molecule interacts with the dipole moment of another.

Question 39

for ion dipole interactions,, does the strength decrease with distance

Answer 39

yes!!

doesn’t decrease as fast as a dipole dipole interaction tho

Question 40

how do induced dipoles occur

Answer 40

when the charge on molecule induced a dipole on another.

aka the e- density may move away from the incoming molecule due to its own e- density

Question 41

example of where induced dipoles occur

Answer 41

between:
a quaternary ammonium ion
aromatic ring

Question 42

what must happen to the polar regions of a drug and it’s target before they interact

Answer 42

they are solvated,, they must then be desolvated (energy put in to remove h2o) to increase entropy,, helps binding interactions

Question 43

does desolation require energy

Answer 43

yes!!
it’s also necessary for the target and drug to interact.

stabilisation energy gained through the DT interaction must be larger than this. (aka the energy needed to desolvate)

Question 44

what part of the drug target and the drug aren’t solvated

Answer 44

the hydrophobic regions

Question 45

what do water molecules do near the hydrophobic regions of the drug and it’s target

Answer 45

they form an ordered layer as they interact

Question 46

what effect does the water molecules near the hydrophobic regions do to the drug and target

Answer 46

reduces its entropy.

makes its entropy negative
(more ordered bc the water molecules are nicely organised by the hydrophobic region)

Question 47

what happens to the ordered water molecules near the hydroponic drug and target regions when the hydrophobic regions interact

Answer 47

they are freed!!

aka entropy increases as the water molecules are no longer nicely organised by the hydrophobic regions

it’s beneficial to the binding energy