Efficient Separation of Nucleic Acids with Different Secondary Structures by Metal-Organic Frameworks

Efficient Separation of Nucleic Acids with Different Secondary Structures by Metal-Organic Frameworks
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利用金属有机框架有效分离不同二级结构的核酸

DOI:
10.1021/jacs.9b10936
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发表时间:
2020
影响因子:
15
通讯作者:
Zhou Xiang
Zhou Xiang
中科院分区:
化学1区
文献类型:
--
作者:
Peng Shuang;Bie Binglin;Jia Hongnan;Tang Heng;Zhang Xiong;Sun Yuqing;Wei Qi;Wu Fan;Yuan Yushu;Deng Hexiang;Zhou Xiang

文献摘要

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我们报告使用金属有机框架(MOFs)的选择性分离的核酸(DNA和RNA)通过大小,形状,长度和构象转换的能力不同的二级结构。三种具有精确控制的孔环境的MOF,Co-IRMOF-74-II、-III和-IV,分别由Co 2+和有机连接体(II、III和IV)组成,用于将核酸从溶液包含到它们的孔中。通过圆二色光谱证明了这是一个从无序自由态到受限有序态的自发过程。确定了三个关键因素:(1)空间位阻诱导的尺寸选择,(2)稳定性诱导的构象转变能选择,和(3)分子量选择。这些选择规则用于从多种核酸的复杂混合物中提取具有柔性和不稳定二级结构的核酸,将具有刚性和稳定二级结构的那些留在母液中。这提供了通过核酸的不同结构特征大量分离和富集核酸的可能性,这在核酸的全基因组结构测量中是非常期望的。与依赖于特异性结合抗体或配体的方法不同,这种MOF方法能够选择具有相似二级结构特征的所有种类的核酸;因此,它适合于同时处理大量种类和数量的核酸。这种方法也有可能收集有关二级结构生物分子折叠稳定性的信息。
We report the use of metal–organic frameworks (MOFs) for the selective separation of nucleic acids (DNA and RNA) with different secondary structures through size, shape, length, and capability of conformational transition. Three MOFs with precisely controlled pore environments, Co-IRMOF-74-II, -III, and -IV, composed of Co2+and organic linkers (II, III, and IV), respectively, were used for the inclusion of nucleic acid into their pores from the solution. This was proven to be a spontaneous process from disordered free state to restricted ordered state via circular dichroism (CD) spectroscopy. Three critical factors were identified for their inclusion: (1) size selection induced by steric hindrance, (2) conformation transition energy selection induced by stability, and (3) molecular weight selection. These selection rules were used to extract nucleic acids with flexible and unstable secondary structures from complex mixtures of multiple nucleic acids, leaving those with rigid and stable secondary structures in the mother liquor. This provides the possibility to separate and enrich nucleic acids in bulk through their different structure feature, which is highly desirable in genome-wide structural measurement of nucleic acids. Unlike methods that rely on specific binding antibodies or ligand, this MOF method is capable of selecting all kinds of nucleic acids with similar secondary structure features; therefore, it is suitable for the handling of a large variety and quantity of nucleic acids at the same time. This method also has the potential to gather information about the folding stability of biomolecules with secondary structures.