Selective Disruption of Survivin's Protein-Protein Interactions: A Supramolecular Approach Based on Guanidiniocarbonylpyrrole

Abstract

Targeting specific protein binding sites to interfere with protein-protein interactions (PPIs) is crucial for the rational modulation of biologically relevant processes. Survivin, which is highly overexpressed in most cancer cells and considered to be a key player of carcinogenesis, features two functionally relevant binding sites. Here, we demonstrate selective disruption of the Survivin/Histone H3 or the Survivin/Crm1 interaction using a supramolecular approach. By rational design we identified two structurally related ligands (L_NES and L_HIS ), capable of selectively inhibiting these PPIs, leading to a reduction in cancer cell proliferation.

Keywords: CL-FEP; cancer; molecular recognition; supramolecular chemistry; survivin.