Sequence-specific binding behavior of coralyne toward triplex DNA: An ultrafast time-resolved fluorescence spectroscopy study

Abstract

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 than 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 G-containing triplex, the fluorescence of coralyne is markedly quenched owing to photoinduced electron transfer (PET) of coralyne with G base. Systematic studies show that the PET rates are sensitive to the binding configuration and local microenvironment, from which coexisting binding modes of monomeric (full and partial) intercalation and aggregate stacking along 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 important roles 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.

Fluorescence Quenching Dynamics of 2-Amino-7-methyl-1,8-naphthyridine in Abasic-Site-Containing DNA Duplexes for Nucleobase Recognition

“…(iii) A further comparative experiment was performed, showing that the fluorescence decay kinetics of AMND is not affected at all when adding the fully paired double-strand ds-(GGG)/d­(CCC). Although some planar π-conjugate fluorescent molecules can intercalate into base pairs of DNA duplexes by π-stacking interactions, , our results here reveal that the AMND molecule cannot intercalate into base pairs in common dsDNA without abasic sites. Thus, there is a lack of electron transfer and lack of fluorescence quenching when adding common ds-DNA.…”

“…The broad absorption band of AMND at 343 nm undergoes peak splitting, while the intensity decreases and the band becomes narrower, as a result of π-stacking interactions of AMND with flanking bases. The stacking geometry may result in a weaker oscillator strength responsible for the absorption reduction and formation of new absorption peaks that are related to a new electronic state transition. , Moreover, the decrease of absorption intensity of AMND follows the order d­( GXG )/d­(CCC) duplex > d­(G AXA G)/d­(CTCTC) duplex > d­(G TXT G)/d­(CACAC) duplex, implying that the degree of π-stacking interactions of AMND with flanking bases also follows the order guanine > adenine > thymine. Meanwhile, the steady-state fluorescence spectra were performed.…”

“…The stacking geometry may result in a weaker oscillator strength responsible for the absorption reduction and formation of new absorption peaks that are related to a new electronic state transition. 20,22 between electron donor guanine and acceptor AMND as well as the largest degree of π-stacking interactions of AMND with guanine.…”