Dipartimento di Medicina Sperimentale, Universita' di Milano-Bicocca, via Cadore 48, Monza (MI) 20052, Italy.
Nucleic Acids Res. 2010 Nov;38(20):7089-99. doi: 10.1093/nar/gkq597. Epub 2010 Jul 3.
Herein, we study the nanomechanical characteristics of single DNA molecules in the presence of DNA binders, including intercalating agents (ethidium bromide and doxorubicin), a minor groove binder (netropsin) and a typical alkylating damaging agent (cisplatin). We have used magnetic tweezers manipulation techniques, which allow us to measure the contour and persistence lengths together with the bending and torsional properties of DNA. For each drug, the specific variations of the nanomechanical properties induced in the DNA have been compared. We observed that the presence of drugs causes a specific variation in the DNA extension, a shift in the natural twist and a modification of bending dependence on the imposed twist. By introducing a naive model, we have justified an anomalous correlation of torsion data observed in the presence of intercalators. Finally, a data analysis criterion for discriminating between different molecular interactions among DNA and drugs has been suggested.
在此,我们研究了单链 DNA 分子在 DNA 结合剂存在下的纳米力学特性,包括嵌入剂(溴化乙锭和阿霉素)、小沟结合剂(萘替普林)和典型的烷化损伤剂(顺铂)。我们使用了磁镊操作技术,该技术允许我们测量 DNA 的轮廓和持久长度以及弯曲和扭转特性。对于每种药物,我们比较了其在 DNA 中引起的纳米力学特性的具体变化。我们观察到,药物的存在会导致 DNA 延伸的特定变化,自然扭转的偏移以及对所施加的扭转的弯曲依赖性的改变。通过引入一个简单的模型,我们证明了在嵌入剂存在下观察到的扭转数据的异常相关性。最后,提出了一种用于区分 DNA 与药物之间不同分子相互作用的数据分析标准。