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富含胞嘧啶的DNA聚集体的结构多样性:甲虫状纳米结构的异常自组装

The structural diversity of C-rich DNA aggregates: unusual self-assembly of beetle-like nanostructures.

作者信息

Protopopova A D, Tsvetkov V B, Varizhuk A M, Barinov N A, Podgorsky V V, Klinov D V, Pozmogova G E

机构信息

Biophysics Department, Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, 119435, Russia.

出版信息

Phys Chem Chem Phys. 2018 Jan 31;20(5):3543-3553. doi: 10.1039/c7cp05380k.

DOI:10.1039/c7cp05380k
PMID:29336444
Abstract

We studied the ability of oligonucleotides CT (n = 2, 5, 7, 9, 12, 25) to form an intermolecular i-motif using circular dichroism, ultra-violet spectroscopy, nuclear magnetic resonance, high-resolution atomic force microscopy, high-performance liquid chromatography, and molecular dynamics simulations. The arrangement of single-stranded oligonucleotides in multimer i-motifs was very unusual: C-tracts of different oligonucleotides followed each other consecutively in order to fold into a closed intermolecular i-motif core with minimal loops (one cytidine in a loop spanning over a minor groove, three cytidines in a loop over a major groove); intact T-tracts protruded from predefined loci allowing visualization of beetle-like nanostructures by atomic force microscopy. The same structures were formed from analogous biotinylated oligonucleotides demonstrating one of the potential applications of such structures as carriers of multiple functional groups. Our findings open up possibilities for the rational design of pH-sensitive DNA aggregates and evaluation of the efficiency of their assembly.

摘要

我们使用圆二色性、紫外光谱、核磁共振、高分辨率原子力显微镜、高效液相色谱和分子动力学模拟等方法,研究了寡核苷酸CT(n = 2、5、7、9、12、25)形成分子间i-基序的能力。单链寡核苷酸在多聚体i-基序中的排列非常独特:不同寡核苷酸的C链依次相连,以折叠成具有最小环(跨越小沟的环中有一个胞嘧啶,跨越主沟的环中有三个胞嘧啶)的封闭分子间i-基序核心;完整的T链从预定义位点突出,通过原子力显微镜可观察到甲虫状纳米结构。由类似的生物素化寡核苷酸形成了相同的结构,证明了此类结构作为多官能团载体的潜在应用之一。我们的研究结果为pH敏感DNA聚集体的合理设计及其组装效率评估开辟了可能性。

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