lecture 1🅱️ Flashcards
list possible protein drug targets
- proteins
- receptors
- enzymes
- transport proteins
- structural proteins (tubulin)
are drug targets large or small molecules
large molecules
aka macromolecules
are drugs smaller or larger than their targets
they’re smaller
how do drugs interact with their targets
they interact by binding to binding sites
what is a binding site on a drug target
- a hydrophobic hollow // cleft on the surface of the macromolecule
macromolecule = target
what type of bonding is involved when drugs bind to macromolecule binding sites
intermolecular bonds
aka bonds between molecules!!
what equilibrium are most drugs a part of
equilibrium of either being bonded to a macromolecule or free
importance of functional groups
they make up binding groups as they are involved in binding interactions
what is a binding region
specific regions within the binding site that are involved in binding interactions
when a binding interaction occurs what 2 things normally line up
binding regions on the target
binding groups on the drug
when does a binding site change shape to accommodate the drug
during induced fit!!!
caused by bonding interactions
what does the induced fit model cause
causes a change in the binding site shape
what does the induced fit model alter
the shape of the macromolecule
the shape of the binding site
important pharmacological effect of the drug
what is the strongest intermolecular bond force
ionic // electrostatic bond
between what groups do ionic // electrostatic bonds form
between groups of opposite charge
electrostatic bond force and distance relationship
inversely proportional
where do stronger electrostatic bonds form
in hydrophobic environments
as distance increases,; how fast does the bond force decrease by
not that much tbh
it decreases but much slower than other intermolecular forces
what initial interaction is most important when a drug enters the binding site
ionic bonds!!
do hydrogen bonds vary in strength
yes!!!
order electrostatic, hydrogen and VDW interactions
electrostatic
hydrogen
VDW
what atom bonds with H to form a H bond
N, O
describe the heteroatom
electron rich
describe the H in hydrogen bonding
e- deficient
what is the e- deficient hydrogen bond called
hydrogen bond donor
what is the electron rich heteroatom called in hydrogen bonding
hydrogen bond acceptor
describe hydrogen bonding
H and an N or O
involved orbitals + is directional
XH bond points towards the Y to form a linear, 180 molecule
strong hydrogen bond acceptors
carboxylate ion
phosphate ion
tertiary amine
moderate hydrogen bond acceptor
carboxylic acid
amide
oxygen
ketone
ester
ether
alcohol
poor hydrogen bond acceptors
fluorine
chlorine
aromatic amine
aromatic ring
sulfur
describe VDW
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
when can dipole dipole interactions occur
- 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.
what happens to the dipoles when the target and drug get closer
they align + orientates the molecule in the binding site
is orientation of the molecule always a benefit in dipole alignment
nope!!
can be beneficial or detrimental depending on if the binding groups are positioned correctly or not
does the strength of a dipole dipole interaction decrease with distance
yup!!!!
less quickly than VDW but more quickly than electrostatic forces//interactions
describe a molecule moving towards a binding site using dipole dipole interactions
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!!
what dipole interaction is stronger than a dipole dipole interaction
an ion dipole interaction
when do ion dipole interactions occur
when the charge on one molecule interacts with the dipole moment of another.
for ion dipole interactions,, does the strength decrease with distance
yes!!
doesn’t decrease as fast as a dipole dipole interaction tho
how do induced dipoles occur
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
example of where induced dipoles occur
between:
a quaternary ammonium ion
aromatic ring
what must happen to the polar regions of a drug and it’s target before they interact
they are solvated,, they must then be desolvated (energy put in to remove h2o) to increase entropy,, helps binding interactions
does desolation require energy
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)
what part of the drug target and the drug aren’t solvated
the hydrophobic regions
what do water molecules do near the hydrophobic regions of the drug and it’s target
they form an ordered layer as they interact
what effect does the water molecules near the hydrophobic regions do to the drug and target
reduces its entropy.
makes its entropy negative
(more ordered bc the water molecules are nicely organised by the hydrophobic region)
what happens to the ordered water molecules near the hydroponic drug and target regions when the hydrophobic regions interact
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
