W8 - Binding Flashcards
What controls the speed of drug reaching the receptor
it is controlled by diffusion
what type of bonding allows the drug to fit into the binding site
electrostatic
hydrophobic
hydrogen
how can we describe the binding of the drugs
the binding is in an dynamic equilibrium so the drug does not remain bound forever
Describe how charges affect binding
the substrate and the receptor can have a net charge
if they are the same they repel making it harder to bind
if they are opposite they pull giving a higher affinity for binding
Describe how lipophilicity and polarity affects binding
if the substrate and receptor are the same i.e both lipophilic or both polar then they have a higher affinity for binding
if the substrate and receptor are different it makes it harder to bind and thus has a lower affinity
Describe how the shape of a substrate and receptor affects binding
if that shape of the substrate can interact with the receptor it has a higher affinity for binding… the highest affinity would be for them to be complementary but often this may not be the case.
How can we measure drug binding
Receptor + detectable hot ligand = Measure binding
What is specific binding
total label bound subtracting binding that occurs when an excess of an unlabeled compound present
What does a specific binding plot tell us
Number of receptor sites (Bmax) and dissociation constant which is a measure of affinity (Kd)
What is Ka equal to
K+1 / K - 1
What is Kd equal to
Kd = K-1/K+1
what is binding normally presented as graphically
semi log or scatchard plot
why is concentration often plotted on a log scale
easiest way to determine Kd
why is it plotted on a scatchard plot
Bmax = x axis interception
Slope = -1/Kd
Plots bound vs bound free
what is KD at equillibrium
it is the concentration of ligand required to bind 50% of available binding site
How do we denote competing ligand
X
what is RX
receptor competitor complex
What is Ki
concentration of radio ligand which is dependent on the radioligand used
what do binding studies tell us
Determines the number of binding sites
Measures the affinity through KD and KI
What does it mean if a drug has high affinity and low selectivity
it can bind well to many receptors but due to it being at mulitple receptors it is not selective
what are the 3 factors that make a drug selective
Ability activate the receptor
Where the drug binds to the receptor
Tissue selectivity
What is the occupational model of agonism (Clarke
agonist binds to a receptor it causes a conformal change and an effect
