Turning Peptide Ligands into Small-Molecule Inhibitors of Protein-Protein Interactions

Abstract

Proline makeover: Truncation and extensive chemical modification of a peptide ligand yielded a biologically active, cell-permeable, peptidomimetic, small-molecule inhibitor of a protein-protein interaction. A key step in this transformation was the replacement of a tetraproline motif by two conformationally constrained diproline units that retain the molecule's PPII helix.

Keywords: EVH1 domain; inhibitors; peptidomimetics; polyproline ligands; protein-protein interactions.