An Orthosteric Inhibitor of the Ras-Sos Interaction

Mimics of α-helices on protein surfaces have emerged as powerful reagents for antagonizing protein-protein interactions, which are difficult to target with small molecules. Herein we describe the design of a cell-permeable synthetic α-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.