School of Chemistry, University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK.
Department of Chemistry, University of Warwick, Gibbet Hill, Coventry, CV4 7AL, UK.
Chemistry. 2020 Apr 16;26(22):4980-4987. doi: 10.1002/chem.202000458. Epub 2020 Mar 9.
The metallation of nucleic acids is key to wide-ranging applications, from anticancer medicine to nanomaterials, yet there is a lack of understanding of the molecular-level effects of metallation. Here, we apply single-molecule fluorescence methods to study the reaction of an organo-osmium anticancer complex and DNA. Individual metallated DNA hairpins are characterised using Förster resonance energy transfer (FRET). Although ensemble measurements suggest a simple two-state system, single-molecule experiments reveal an underlying heterogeneity in the oligonucleotide dynamics, attributable to different degrees of metallation of the GC-rich hairpin stem. Metallated hairpins display fast two-state transitions with a two-fold increase in the opening rate to ≈2 s , relative to the unmodified hairpin, and relatively static conformations with long-lived open (and closed) states of 5 to ≥50 s. These studies show that a single-molecule approach can provide new insight into metallation-induced changes in DNA structure and dynamics.
金属化核酸在从抗癌药物到纳米材料的广泛应用中是关键，但对金属化的分子水平影响缺乏了解。在这里，我们应用单分子荧光方法来研究有机锇抗癌配合物与 DNA 的反应。使用Förster 共振能量转移（FRET）来表征单个金属化 DNA 发夹。尽管整体测量表明是一个简单的两态系统，但单分子实验揭示了寡核苷酸动力学中的潜在异质性，这归因于富含 GC 的发夹茎部的不同程度的金属化。金属化发夹显示快速的两态转变，与未修饰的发夹相比，打开率增加了两倍，达到 ≈2 s，并且具有相对静态的构象，其开放（和关闭）状态的寿命为 5 到 ≥50 s。这些研究表明，单分子方法可以为金属化引起的 DNA 结构和动力学变化提供新的见解。
