Triplex DNA structure has potential therapeutic application in inhibiting the expression of genes involved in
cancer and other diseases. As
a DNA-targeting antitumor and
antibiotic drug,
coralyne shows a remarkable binding propensity to triplex over canonical duplex and thus can modulate the stability of triplex structure, providing a prospective gene targeting strategy. Much less is known, however, about
coralyne-binding interactions with triplex. By combining multiple steady-state spectroscopy with ultrafast fluorescence spectroscopy, we have investigated the binding behaviors of
coralyne with typical triplexes. Upon binding with a G-containing triplex, the fluorescence of
coralyne is markedly quenched owing to the photoinduced electron transfer (PET) of
coralyne with the G base. Systematic studies show that the PET rates are sensitive to the binding configuration and local microenvironment, from which the coexisting binding modes of monomeric (full and partial) intercalation and aggregate stacking along the
sugar-
phosphate backbone are distinguished and their respective contributions are determined. It shows that
coralyne has preferences for monomeric intercalation within CGG triplex and pure TAT triplex, whereas CGC+ triplex adopts mainly backbone binding of
coralyne aggregates due to charge repulsion, revealing the sequence-specific binding selectivity. The
triplex-DNA-induced aggregation of
coralyne could be used as a probe for recognizing the water content in local
DNA structures. The strong π-π stacking of intercalated
coralyne monomer with base-triplets plays an important role in stabilizing the triplex structure. These results provide mechanistic insights for understanding the remarkable propensity of
coralyne in selective binding to
triplex DNA and shed light on the prospective applications of
coralyne-triplex targeted anti-gene
therapeutics.