NF unit 2

applied drug design

what is the function of an agonist

binds to the ligand binding site and triggers a chain of intracellular events to transduce a response

this then leads to what?

tissue response

what is the function of an antagonist

bind to the same binding site and obscure the receptor so the agonist can no longer access it

this does what?

blocks the response

selectivity is defined as — —

this means that a ligand (— or —) has higher — for one receptor over another

as you increase the concentration of a ligand eventually it will start to bind to other receptors as well

if a drug has better selectivity, it means you can use it a high concentration without worrying about it binding to off target sites/other receptors and having adverse effects

relative affinity, agonist, antagonist, affinity

what are the 3 major ways you can quantify selectivity

response profiles, concentration response curves, radioligand binding

what is the most up to date and selective one?

radioligand binding

concentration response curves with non selective and selective agonist

done

what does radioligand binding determine?

binding affinity of ligand for binding site

what is not a factor for radioligand binding?

efficacy

so there is no distinction between?

agonists and antagonists

what are the two types of radioligand binding

saturation binding, competition binding

in saturation binding the drug of interest is labelled with a — label and then by measuring the — you can measure how much drug is present in any given sample

radioactive, radioactivity

when you add your radiolabelled drug you will get 2 types of binding- what are they

specific binding, non specific binding

what happens with specific binding

drug binds to target receptor

what is non specific binding

drug binds to membranes and other proteins that are not the ligands receptor

which type of binding is saturable?

specific binding

what is the equation for total binding?

specific binding + non specific binding

what is a cold ligand?

unlabelled version of the drug

what is a hot ligand?

radiolabelled drug

saturation binding analysis

done

what can you obtain from saturation binding?

KD

what can you then obtain from K_D?

affinity constant KA

what is the affinity constant equation

1/KD

this means a low KD means a — affinity

high

maximum specific binding is equivalent to?

total number of receptors present

in competition binding, what amount of radioligand is added?

one concentration

during competition binding, the radioligand is — from receptors with — —

displaced, unlabelled ligand

affinity is calculated based on?

relative affinity and concentration of radioligand used