title: Direct Ras Inhibitors Identified from a Structurally Rigidified Bicyclic Peptide Library.
abstract: A one-bead-two-compound (OBTC) library of structurally rigidified bicyclic peptides was chemically synthesized on TentaGel microbeads (90 μm), with each bead displaying a unique bicyclic peptide on its surface and a linear encoding peptide of the same sequence in its interior. Screening of the library against oncogenic K-Ras G12V mutant identified two classes of Ras ligands. The class I ligands apparently bind to the effector-binding site and inhibit the Ras-Raf interaction, whereas the class II ligand appears to bind to a yet unidentified site different from the effector-binding site. These Ras ligands provide useful research tools and may be further developed into therapeutic agents.
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18 Avenue, Columbus, Ohio 43210, USA.
authors.forename: Punit
authors.initials: P
authors.lastname: Upadhyaya
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18 Avenue, Columbus, Ohio 43210, USA.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18 Avenue, Columbus, Ohio 43210, USA.
authors.forename: Nurlaila A A
authors.initials: NA
authors.lastname: Habir
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18 Avenue, Columbus, Ohio 43210, USA.
authors.forename: Dehua
authors.initials: D
authors.lastname: Pei
keywords: Bicyclic peptide; K-Ras; Protein-protein interaction; combinatorial library; inhibition