A triphenylamine derivative as a naked-eye and light-up fluorescent probe for G-quadruplex DNA

Abstract

G-quadruplex (G4) DNAs have attracted considerable interest because of their important biological functions and medical applications. Searching for highly specific binding molecules is important for the basic research of G4 DNA, as well as the design of novel anticancer drugs. Previous, we have developed a quinolone-substituted triphenylamine probe (TPA-2b) with selectivity to G4 DNAs. Herein, we further designed and synthesized a hydroxyethyl functionalized derivative (TPA-3) and investigated the interactions with G4 DNAs and living cells. TPA-3 was found to express significant fluorescence enhancement upon its interaction with G4 DNAs while shows almost no response to non-quadruplex DNAs. The distinction can even be easily distinguished by the naked eye under UV light. The spectral analysis showed TPA-3 bound to G4 DNAs mainly through intercalative binding mode. CD study results indicated TPA-3 did not disturb the conformation of G4 structure. Cellular uptake assay suggested that TPA-3 could pass through membrane and enter living cells. Our results suggested the side chain of core structure could change the binding affinity to G4 DNAs, as well as the interaction with living cells. Thus, this study gives some clues to design new G4 DNA probes with high selectivity, sensitivity, and biological imaging applications.