Metallation-induced heterogeneous dynamics of DNA revealed by single-molecule FRET.
Metallation-induced heterogeneous dynamics of DNA revealed by single-molecule FRET.
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DOI：
10.1002/chem.202000458
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发表时间：
2020-01
期刊：
影响因子：
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通讯作者：
Raul Berrocal-Martin;C. Sanchez‐Cano;Cookson K. C. Chiu;R. J. Needham;P. Sadler;S. Magennis
中科院分区：
文献类型：
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作者：
Raul Berrocal-Martin;C. Sanchez‐Cano;Cookson K. C. Chiu;R. J. Needham;P. Sadler;S. Magennis
核酸的金属化是从抗癌药物到纳米材料的广泛应用的关键，但人们对金属化的分子水平的影响缺乏了解。在这里，我们应用单分子荧光方法研究了一种有机Os抗癌化合物与DNA的反应。用Förster共振能量转移(FRET)对单个金属DNA发夹进行了表征。虽然系综测量提出了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潜在的异质性，这可归因于富含GC的发夹茎的不同程度的金属化。与未修饰的发夹相比，金属化的发夹显示出快速的双态转变，开放速率提高到~2 S-1，而相对静态的构象则表现出从5 S到≥50 S的长寿命开放(和闭合)状态。这些研究表明，单分子方法可以为金属诱导的DNA结构和动力学变化提供新的见解。
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 characterized 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-1, relative to the unmodified hairpin, and relatively static conformations with long-lived open (and closed) states of 5 s to ≥ 50 s. These studies show that a single-molecule approach can provides new insight into metallation-induced changes in DNA structure and dynamics.