Modulators of Protein-Protein Interactions

Protein-protein interactions (PPIs) are operative at all levels of cellular organization and function. Peptide stapling and hydrogen-bond surrogates, among other approaches, were used to improve the metabolic stability and cell membrane permeability of peptides, which is an important step toward PPI targeting therapeutics. Oligomeric structures such as foldamers represent highly promising, metabolically stable secondary structure mimics, while the structural diversity and biological relevance of natural products will continue to be a rich source for PPI drug discovery. Virtual screening can offer a cost-effective alternative to high-throughput screening (HTS), while supramolecular approaches represent novel orthogonal entries for PPI modulation. Accordingly, depending on the general principle of these screening methods and the biophysical characteristics that the proteins of interest have to possess, a differentiation can be made between surface based and proximity based assays.