Wandering beyond small molecules: peptides as allosteric protein modulators

Recent years have seen the rise of allosteric modulation as an innovative approach for drug design and discovery, efforts which culminated in the development of several clinical candidates. Allosteric modulation of many drug targets, including mainly membrane-embedded receptors, have been vastly explored through small molecule screening campaigns, but much less attention has been paid to peptide-based allosteric modulators. However, peptides have a significant impact on the pharmaceutical industry due to the typically higher potency and selectivity for their targets, as compared with small molecule therapeutics. Therefore, peptides represent one of the most promising classes of molecules that can modulate key biological pathways. Here, we report on the allosteric modulation of proteins (ranging from G protein-coupled receptors to specific protein-protein interactions) by peptides for applications in drug discovery.