Design and Synthesis of Highly Potent and Plasma‐Stable Dimeric Inhibitors of the PSD‐95–NMDA Receptor Interaction

On the double: Dimerization of monomeric peptide ligands towards the PDZ domains of the protein PSD-95 (postsynaptic density 95) leads to potent inhibitors of protein–protein interactions with stability in blood plasma. Optimization of the length of the polyethylene glycol linker results in unprecedented affinity for inhibitors of the PDZ1-2 domain (see picture).