A Chemical Library Approach to Organic-Modified Peptide Ligands for PDZ Domain Proteins: A Synthetic Thermodynamic and Structural Investigation

摘要

PDZ domains are members of the protein interaction domain family,[] semi-autonomous modules embedded within larger signaling proteins that impart a degree of exclusivity to the binding properties of their hosts. As mediators of mammalian protein-protein interactions that number in the hundreds, PDZ domains are party to a correspondingly large array of cellular processes, most notably those that regulate or support neuronal activities.[] Specific, bioavailable molecular probes are needed to foster biological inquiries into their functions; towards this end, we report our recent progress in the discovery and development of PDZ domain inhibitors.