Specific inhibition of the Survivin-CRM1 interaction by peptide-modified molecular tweezers.

ABSTRACT: Survivin's dual function as apoptosis inhibitor and regulator of cell proliferation is mediated via its interaction with the export receptor CRM1. This protein-protein interaction represents an attractive target in cancer research and therapy. Here, we report a sophisticated strategy addressing Survivin's nuclear export signal (NES), the binding site of CRM1, with advanced supramolecular tweezers for lysine and arginine. These were covalently connected to small peptides resembling the natural, self-complementary dimer interface which largely overlaps with the NES. Several biochemical methods demonstrated sequence-selective NES recognition and interference with the critical receptor interaction. These data were strongly supported by molecular dynamics simulations and multiscale computationa

SUBMITTER: Meiners A 

PROVIDER: S-EPMC7940618 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature