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

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.