Increase your competitive edge by staying longer
Benefits
The efficacy of inhibiting a target is commonly dependent on the residence time of the ligand. Therefore, two different ligands with identical affinity could differ significantly in clinical efficacy due to differences in kinetics. Gaining control over the association and dissociation rate of your inhibitor could provide a competitive advantage. In addition, the discovery of inhibitors with unexpectedly slow dissociation rates could provide an inventive step, making your compounds patentable.
Deliverables
1) Mechanism and complexity of the interaction
2) Kinetic constants (i.e. kon, koff and KD)
3) Same data for competitor compounds
Technical Details
The analysis of protein-ligand interactions are performed by SPR biosensor-based experiments. This entails an immobilization of the target protein to a sensor chip followed by injection of a concentration series of reference and test compounds. Analysis of the response with respect to injection time allows for determination of rate constants as well as dissociation constants (for an example, see figure below). By analysis of the curvature of the response, a mechanism and a stoichiometry could be assigned to the interaction.
Figure. Examples of kinetic traces of two inhibitors of HIV-1 RT. Injection starts at 0 s and ends at 60 s where buffer is injected to study the dissociation phase.
