Classification of drugs?
Based on identifying interactions between ligands and receptor macromolecules at a site that recognise the endogenous agonist
The site on a receptor that recognise the endogenous agonist
What sites can ligands bind to?
Orthosteric and allosteric sites.
MWC model: what are the two confirmation that protein exisit in?
Proteins exist in two distinct confirmation
T and R state
When is T state favoured over the R state?
In the absence of enzyme
What is the equilibrium constant
Visual the MWC model?
The binding site on a receptor macromolecule that is recognised by the endogenous agonist for that receptor
Binding site on a receptor macromolecule that is non-overlapping and spatially distinct from but conformationally linked to the arthosteric binding site.
Name the 4 potential advantages of allosteric ligands?
Structural features that govern binding of allosteric ligand and orthosteric ligands can be different.
- Targeting the allosteric site may allow the development of ligands with greater receptor subtype selectivity because of higher sequence divergence.
- Ligands binding to allosteric sites will modify the confirmation of a receptor.
- Preserve spatial and temporal selectivity of endogenous signalling.
Ligand that binds to an allosteric site on a receptor macromolecule and alters the receptor state.
Resulting in a biological response.
Name the two types of allosteric agonists?
The differences between them
Conventional allosteric agonist: increase receptor activity
Allosteric inverse agonist: decrease the receptor activity.
Ligand that modifies the action of an orthosteric agonist, endogeneous activitor or antagonist.
By combinding with an allosteric site on the receptor.
Name the two types of allosteric modulators and the differences?
Positive allosteric modulator:
Increases the action of an orthosteric agonist.
Negative allosteric modulator:
Decreases the action of an orthosteric agonist.
Neutral allosteric ligand?
Ligand that combines with an allosteric site on a receptor but does not alter the action of an orthosteric agonist, activator or antagonist.
Prevents the binding of other allosteric ligands
Interaction between ligands that bind to the same recognition site or one that overlaps on the receptor macromolecule.
Can occur between different orthosteric ligands or different allosteric ligands.
Engages on orthosteric and allosteric site on a receptor macromolecule.