Drug-Target Interactions Flashcards
what is cooperativity due to?
ligand pre-organisation / target plasticity
what does enthalpy-entropy compensation often lead to?
negative cooperativity
most water molecules occupying a ligand binding site are ..
disordered + easily displaced
what are PDE10 inhibitors ion interest as?
antipsychotics
charged HB are shorter than …
uncharged HB
what is the angular preference in HB dictated by?
acceptor atom / functional group
when does the acceptor ability drop?
when lone pair = conjugated
e.g. O atom of diphenyl ether doesn’t HB
when is sulfonyl useful?
when wanting to form HB in hydrophobic pocket
weak HB are …
longer than strong ones
acetyl units and iodine are roughly …
isosteric
what is halogen bonding from chlorine atoms in triclosan thought to be key in?
bactericidal activity
what is fluorine important in?
drug target interactions due to extreme electronegativity
results in strong dipole
Cl shows a greater degree of …
angle preference than F
the presence of a sigma-hole allows for what?
halogen bonding
what is the sigma-hole?
region of positive electrostatic potential opposite C-X bond
what is the sigma-hole caused by?
s2p2p2 electron configuration
when halogens are positioned close to and over the pi-surface, what arrangement do they prefer?
perpendicular
aromatic CH is preferred to…
halogen over pi-surface contact
what does binding affinity correlate to?
hydrophobic surface area removed from solvent upon complexation
what does a difference in volume allow?
target to retain reasonable flexibility
describe the eg of DPP-IV inhibitors developed to treat type 2 diabetes?
- inc in vol + greater hydrophobicity of F over H
- combine to produce 400 fold inc in binding compared to unsubstituted compound
e-rich, e-poor, e-poor, e-poor aromatics are better than ….
e-rich, e-rich stacks
what do ortho/para e withdrawing substituents increase?
hydrogen acidity + promote T stacked orientation
extension of a methyl group will provide what?
better lipophilic contact
