Applying dynamic combinatorial chemistry (DCC) to medicinal chemistry projects can be a helpful strategy for finding starting points in the drug-discovery process. Especially, when DCC is combined with structure-based or fragment-based drug design approaches, potent compounds can be obtained.
As relevant drug target, 14-3-3 proteins play a role in several diseases and many biological processes. Proteins of this family engage in protein-protein interactions (PPIs), and can do so with numerous different binding partners. By forming these PPIs, these proteins regulate their binding partner’s activity. The activity can be both up- or down-regulated. Finding modulators of PPIs is very challenging via traditional screening approaches.
In this webinar we will briefly introduce DCC, followed by the first application of DCC to a PPI, where we found small-molecule modulators of the PPI of 14-3-3/ synaptopodin. These hit compounds were then evaluated for their biochemical properties via surface plasmon resonance (SPR) and fluorescence polarization (FP) assay.
