Here we report a new study performed at single molecule level on the interaction of the antineoplastic drug Carboplatin and the DNA molecule - the main target of the drug inside cells in cancer chemotherapies. By using optical tweezers, we measure how the mechanical properties of the DNA-Carboplatin complexes changes as a function of the drug concentration in the sample, for two different ionic strengths ([Na] = 150 mM and [Na] = 1 mM). From these measurements, the binding mechanism and the physicochemical (binding) parameters of the interaction were inferred and directly compared to those obtained for the precursor drug Cisplatin under equivalent conditions. As the main conclusion, we show that Carboplatin binds preferentially forming covalent monoadducts in contrast to Cisplatin, which is hydrolyzed easier and presents a higher efficiency in forming covalent diadducts along the double-helix. In addition, we explicitly show that Carboplatin is much less sensitive to ionic strength changes when compared to Cisplatin. These findings provide new insights on the interactions of platinum-based compounds with the DNA molecule, being important to improve the current treatments and in the development of new antineoplastic agents.
In the present study we investigated the binding of the anticancer compound Oxaliplatin to DNA. Using optical tweezers to perform single molecule force spectroscopy, we determined the changes of the mechanical parameters of DNA complexes formed with Oxaliplatin, at high and low ionic strengths. The interaction mechanism and the physical chemistry of the binding were determined from these measurements. In addition, kinetic information on covalent diadduct formation and on DNA compaction by Oxaliplatin were also obtained. All these results were critically compared to those obtained for the related anti-neoplastic compounds Cisplatin and Carboplatin, previously determined under similar experimental conditions. These results provide new information about the action of platinum-based compounds on DNA, being useful to the improvement of current chemotherapies and to the design of novel correlated drugs.
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