Binding modes of a core-extended metalloporphyrin to human telomeric DNA G-quadruplexes

The molecular recognition of human telomeric G-quadruplexes by a novel cationic pi-extended Ni-II-porphyrin (Ni-II-TImidP4) is studied in aqueous solutions via (chir) optical spectroscopy, Fluorescence Resonance Energy Transfer (FRET) melting assay, and computational molecular modeling. The results are systematically compared with the recognition by a conventional meso-substituted Ni-II-porphyrin (Ni-II-TMPyP4), which allows us to pinpoint the differences in binding modes depending on the G-quadruplex topology. Importantly, FRET melting assays show the higher selectivity of Ni-II-TImidP4 towards human telomeric G4 than that of Ni-II-TMPyP4.