title: Influence of macrocyclization on allosteric, juxtamembrane-derived, stapled peptide inhibitors of the epidermal growth factor receptor (EGFR).
abstract: 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.
authors.affiliation: Department of Chemistry and ‡Department of Molecular, Cellular and Developmental Biology, Yale University , New Haven, Connecticut 06520-8107, United States.
authors.forename: Julie K-L
authors.initials: JK
authors.lastname: Sinclair
authors.forename: Alanna
authors.initials: A
authors.lastname: Schepartz
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D010766:Phosphorylation; D011485:Protein Binding
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors