Unfolding of i-Motif DNA Structures Using G-Quadruplex Stabilizing Bisindolylmaleimide Ligands

i-Motif (iM) structures are formed by C-rich DNA strands that complement G-quadruplex (G4)-forming sequences in the genome. Small-molecule ligands that help transiently fold or unfold iM structures provide tools to regulate gene expression. Herein, we demonstrate, using CD studies, NMR titration, and molecular dynamics (MD) simulations, that potent G4 stabilizers, BIM-Pr1 and BIM-Pr2, also interact with telomeric and diverse sets of promoter iM structures, resulting in their destabilization and conformational unfolding. Since the formation of iM and G4 structures is predominantly mutually exclusive, our results have implications for developing ligands that interact with both G4 and iM for biological and sensing applications.