The hydrocarbon-stapled peptide E1(S) allosterically inhibits the kinase activity of the epidermal growth factor receptor (EGFR) by blocking a distant but essential protein-protein interaction: a coiled coil formed from the juxtamembrane segment (JM) of each member of the dimeric partnership.1 Macrocyclization is not required for activity: the analogous unstapled (but alkene-bearing) peptide is equipotent in cell viability, immunoblot, and bipartite display experiments to detect coiled coil formation on the cell surface.