Discovery of a fluorescent, long chain-bridged bispurine that selectively targets the c-MYC G-quadruplex.

G-quadruplexes (G4s) are special nucleic acid structures which are involved in the regulation of some key biological events like transcription and translation, which are now treated as promising therapeutic targets for cancers. Stabilizing the promoter G4 by small-molecule ligands can suppress the c-MYC oncogene transcription, thus inhibiting cancer cell proliferation. So far, targeting the very structure, a number of ligands have been reported. However, most of them showed unsatisfactory specificity to the c-MYC G4 over other G4s, resulting in uncertain side effects. In this contribution, we discovered a new class of bispurines bridged with flexible hydrocarbon chains, which presented somewhat selectivity to the c-MYC G4 possibly by adaptive binding, which then showed clear inhibition on the c-MYC expression rather than other G4-driven oncogenes. Moreover, these novel molecules had the potential to fluorescently label G4s. We believed that this study may shed light on the discovery of new functional small molecules targeting a specific G4 structure.