Bazoni R F, Moura T A, Rocha M S
Departamento de Ciências Naturais, Universidade Federal do Espírito Santo, São Mateus, Espírito Santo 29.932-540, Brazil.
Departamento de Física, Universidade Federal de Viçosa. Viçosa, Minas Gerais 36.570-900, Brazil.
J Phys Chem Lett. 2020 Nov 19;11(22):9528-9534. doi: 10.1021/acs.jpclett.0c02590. Epub 2020 Oct 28.
In the past months, the use of the drug hydroxychloroquine has considerably increased in many countries, associated with a proposed treatment for the COVID-19 disease. Although there is no conclusive evidence about the efficacy of the drug for this purpose, surprisingly there are no conclusive studies in the literature concerning its mechanism of action inside cells, which is related to its interaction with nucleic acids. Here, we performed a robust characterization of the interaction between hydroxychloroquine and double-stranded DNA using single-molecule force spectroscopy and gel electrophoresis. Two different binding modes were identified, namely, minor groove binding for low drug concentrations and intercalation for high drug concentrations, and the sets of binding parameters were determined for each of these modes. Such results have unraveled in detail the molecular mechanism of action of the drug as a DNA ligand.
在过去几个月里，许多国家羟氯喹这种药物的使用量大幅增加，这与一种针对新冠病毒疾病的提议治疗方法有关。尽管对于该药物在此用途上的疗效尚无确凿证据，但令人惊讶的是，文献中也没有关于其在细胞内作用机制的确切研究，而这一机制与其与核酸的相互作用有关。在此，我们使用单分子力谱和凝胶电泳对羟氯喹与双链DNA之间的相互作用进行了全面表征。确定了两种不同的结合模式，即低药物浓度时的小沟结合和高药物浓度时的嵌入，并为每种模式确定了结合参数集。这些结果详细揭示了该药物作为DNA配体的分子作用机制。
