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DNA intercalation by quinacrine and methylene blue: A comparative binding and thermodynamic characterization study

机译：奎纳克林和亚甲蓝的DNA嵌入：比较结合和热力学表征研究

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There is compelling evidence that cellular DNA is the target of many anticancer agents. Consequently, elucidation of the molecular nature governing the interaction of small molecules to DNA is paramount to the progression of rational drug design strategies. In this study, we have compared the binding and thermodynamic aspects of two known DNA-binding agents, quinacrine (QNA) and methylene blue (MB), with calf thymus (CT) DNA. The study revealed noncooperative binding phenomena for both the drugs to DNA with an affinity one order higher for QNA compared to MB as observed from diverse techniques, but both bindings obeyed neighbor exclusion principle. The data of the salt dependence of QNA and MB from the plot of log K versus log [Na+] revealed a slope of 1.06 and 0.93 consistent with the values predicted by theories for the binding of monovalent cations, and have been analyzed for contributions from polyelectrolytic and nonpolyelectrolytic forces. The binding of both drugs was further characterized by strong stabilization of DNA against thermal strand separation in both optical melting and differential scanning calorimetry studies. The binding data analyzed from the thermal denaturation and from isothermal titration calorimetry (ITC) were in close proximity to those obtained from spectral titration data. ITC results revealed the binding to be exothermic and favored by both negative enthalpy and positive entropy changes. The heat capacity changes obtained from temperature dependence of enthalpy indicated -146 and -78 cal/(mol-K), respectively, for the binding of QNA and MB to CT DNA. Circular dichroism study further characterized the structural changes on DNA upon intercalation of these molecules. Molecular aspects of interaction of these molecules to DNA are discussed.
机译：有令人信服的证据表明细胞DNA是许多抗癌药物的靶标。因此，阐明控制小分子与DNA相互作用的分子性质对于合理的药物设计策略至关重要。在这项研究中，我们比较了两种已知的DNA结合剂奎纳克林（QNA）和亚甲基蓝（MB）与小牛胸腺（CT）DNA的结合和热力学方面。这项研究揭示了两种药物与DNA的非合作结合现象，与MB相比，QNA的亲和力比MB高一阶，但两种结合都遵循了邻居排斥原理。从log K对log [Na +]的关系图得出的QNA和MB的盐依赖性数据显示，斜率分别为1.06和0.93，与理论上预测的单价阳离子结合预测的值一致，并且已经分析了聚电解质的贡献和非聚电解力。两种药物的结合的特征还在于，在光学熔解和差示扫描量热法研究中，DNA对热链分离具有较强的稳定性。从热变性和等温滴定热分析（ITC）分析的结合数据与从光谱滴定数据获得的结合数据非常接近。 ITC结果表明，结合是放热的，并且受到负焓和正熵变化的影响。对于QNA和MB与CT DNA的结合，由焓的温度依赖性获得的热容变化分别表示为-146和-78 cal /（mol-K）。圆二色性研究进一步表征了插入这些分子后DNA的结构变化。讨论了这些分子与DNA相互作用的分子方面。

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