Abstract
We perform time-correlated single-photon counting measurements with 30-ps resolution of the fluorescence emitted by the donor fluorophores of donor–acceptor pairs covalently labeling DNA synthetic oligonucleotides by using a non-commercial single-photon avalanche diode. The measurements allow us to precisely assess the fluorescence resonant energy transfer efficiency of the pairs in solutions containing the oligonucleotides and DNA–ligands, for different ratios of the DNA base-pair to ligand concentrations. A quantitative evaluation of the deformations of DNA double strands following the ligand binding is obtained, as the transfer efficiency is a steep function of the donor-to-acceptor distance. The results lead to an easy and cheap method to discriminate between the binding modes of minor groove and base intercalating ligands.
Highlights
The classic approach used to fight cancer, based on killing cancerous cells by employing radiations or chemotherapy, invariably kills the healthy cells too, often producing severe collateral effects
As ligands that bind in the same way induce similar deformation and denaturation effects on the Oligos with which they interact, that are very different between Minor Groove Binders (MGBs) and Base Intercalators (BI), the results presented here encourage us to propose a protocol for easy and cheap discrimination between minor groove and intercalation binding modes
The binding isotherm obtained for the spectrophotometric titration of calf thymus (CT) DNA with quinacrine dihydrochloride (QUIN) is displayed in Fig. 1(a), in which the absorbance at 434.4 nm is plotted versus P
Summary
The classic approach used to fight cancer, based on killing cancerous cells by employing radiations or chemotherapy, invariably kills the healthy cells too, often producing severe collateral effects. The unwinding of the helices induced by BIs causes an enhanced exposure of the bases to the solvent: mutagenesis is dramatically increased [11,12,13] For this reason, intercalators are dangerous carcinogens, even if their cytotoxicity has been widely exploited to devise antiviral drugs and in chemotherapy This may result in either over-expression or repression of downstream genes [22,23,24,25]. In vivo studies conducted on the MGB Pentamidine have revealed no mutagenic effect in nuclear DNA, and only very weak effects on mitochondrial DNA of yeast [1,26] This result suggests that minor groove binding does not induce indiscriminate mutagenesis on nucleic acids
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