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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 ?m), 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.

SUBMITTER: Upadhyaya P

PROVIDER: S-EPMC4180945 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Direct Ras Inhibitors Identified from a Structurally Rigidified Bicyclic Peptide Library.

Upadhyaya Punit P Qian Ziqing Z Habir Nurlaila A A NA Pei Dehua D

Tetrahedron 20141001 42

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 ...[more]

PMID: 25284901

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