Amino-Acid-Derived Naphthalenediimides as Versatile G-Quadruplex Binders

The design and synthesis of water soluble, amino-acid-functionalised naphthalenediimides (NDIs) as potential ligands of native G-quadruplexes is reported. The NDIs were tested on a panel of oncogene promoters, on the human telomeric sequence h-telo, and on double-stranded DNA. Out of the ligands tested, NDI 3 (N-epsilon-Boc-l-lysine NDI) exhibited a highly discriminating nature by only stabilising the oncogene promoter c-kit2, which is up-regulated up to 80% in ovarian, gastrointestinal, and breast malignancies.