Jonas Nii Nortey Eildal

Blocking cellular protein-protein interactions (PPIs) serves as a potential mean to specifically manipulate with downstream effector molecules and develop more efficient and safe medicine. Furthermore, PPI inhibitors are valuable pharmacological tools to elucidate complex biological phenomena. In our group we focus on a protein domain family named PDZ. These domains are highly abundant in the human proteome and participate in many therapeutical relevant PPIs as modules in larger proteins. PSD-95 is a scaffold protein that interacts with the NMDA receptor through its PDZ domains and thereby involved in stroke (Figure). By using a peptidomimetic approach potent N-alkylated tetrapeptide inhibitors has been identified and are currently investigated in cell-based assays. Alternative strategies for pursuing potent and druglike PDZ domain inhibitors are also being explored.