title: An orthosteric inhibitor of the Ras-Sos interaction.
abstract: 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. Here 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.
authors.affiliation: Department of Chemistry, New York University, New York, New York, USA.
authors.forename: Anupam
authors.initials: A
authors.lastname: Patgiri
authors.forename: Kamlesh K
authors.initials: KK
authors.lastname: Yadav
authors.forename: Paramjit S
authors.initials: PS
authors.lastname: Arora
authors.forename: Dafna
authors.initials: D
authors.lastname: Bar-Sagi
mesh_terms: D000595:Amino Acid Sequence; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D032701:Biomimetics; D002460:Cell Line; D015536:Down-Regulation; D015195:Drug Design; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D020839:Son of Sevenless Protein, Drosophila / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020663:ras Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D009842:Oligopeptides; D020839:Son of Sevenless Protein, Drosophila; D020663:ras Guanine Nucleotide Exchange Factors; D011505:Protein-Tyrosine Kinases