Biaffin Lead optimisation

Biaffin - Service für Biomolekulare Interaktionsanalyse

BIA technology for hit validation and lead optimisation

Hit validation is needed to determine whether a molecule identified in a screen or assay will eventually lead to a drug. Therefore secondary assays generating data about potency, selectivity and functional biochemical activity have to be performed. BIA technology has an enormous capability for the rapid confirmation of hits from high throughput screens by a comprehensive kinetic characterisation of potential lead compounds. Informations about affinities, rates of association and dissociation in complex formation and binding stoichiometries are valuable for a ranking and optimisation of lead compounds. Even compounds binding with low affinity or transient kinetics, often found in early phases of drug development, can accurately be identified.

The kinetic information obtained by functional assays together with the knowledge about structural properties of biomolecules allows predictions on structure activity relationships. Lead optimisation is an iterative process involving computer-assisted molecular modelling, chemical synthesis of new compounds and functional assays. BIA technology is used in lead optimisation by linking compound structural information with a comprehensive kinetic characterisation of ligand binding.

The figure shows the determination of EC50 values for different cAMP analoga in a solution competition assay. The cAMP analoga compete with different immobilised nucleotide analoga on the chip surfaces for the binding sites of a cAMP binding protein. Ranking of these analoga enables the identification of compounds with higher affinity than cAMP itself.