Direct Ras inhibitors identified from a structurally rigidified bicyclic peptide library

作者：Upadhyaya Punit; Qian Ziqing; Habir Nurlaila A A; Pei Dehua^*

来源：Tetrahedron, 2014, 70(42): 7714-7720.

DOI：10.1016/j.tet.2014.05.113

• Bicyclic peptide
• Combinatorial library
• Inhibition
• K-Ras
• Protein-protein interaction

A one-bead-two-compound (OBTC) library of structurally rigidified bicyclic peptides was chemically synthesized on TentaGel microbeads (90 gm), 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.

• 出版日期2014-10-21