An orthosteric inhibitor of the Ras-Sos interaction

Mimics of alpha-helices on protein surfaces have emerged as powerful reagents for antagonizing protein-protein interactions, which are difficult to target with small molecules. Here we describe the design of a cell-permeable synthetic alpha-helix, based on the guanine nucleotide exchange factor Sos, that interferes with Ras-Sos interaction and downregulates Ras signaling in response to receptor tyrosine kinase activation.