Solution structure and conformational dynamics of deoxyxylonucleic acids (dXNA): an orthogonal nucleic acid candidate.

Solution structure and conformational dynamics of deoxyxylonucleic acids (dXNA): an orthogonal nucleic acid candidate.
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脱氧木糖核酸(dXNA)的溶液结构和构象动力学:正交候选核酸

DOI:
10.1002/chem.201102509
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发表时间:
2012
期刊:
影响因子:
--
通讯作者:
P. Herdewijn
P. Herdewijn
中科院分区:
--
文献类型:
--
作者:
M. Maiti;V. Siegmund;M. Abramov;E. Lescrinier;H. Rosemeyer;M. Froeyen;A. Ramaswamy;A. Ceulemans;A. Marx;P. Herdewijn

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正交核酸是化学修饰的核酸聚合物,其不能与天然核酸转移信息,因此可用于合成生物学以独立地存储和转移遗传信息。最近,有人提出木糖-DNA(dXNA)可以被认为是正交系统的潜在候选者。在本文中,我们提出了两种自我互补的完全修饰的dXNA寡核苷酸的溶液结构和构象分析,如通过CD和NMR光谱所确定的。这些研究是dXNAs结构正交性的初步实验证明。在水溶液中,dXNA双链体主要形成线性梯状(1型)结构。这是采用梯状结构的呋喃糖核酸的第一个实例。在盐的存在下,两种类型的双链形式之间存在平衡。合成了相应的核苷三磷酸(dXNTPs),并通过使用几种天然的和突变的DNA聚合酶来评估它们被掺入到生长的DNA链中的能力。尽管dXNA具有结构正交性,但DNA聚合酶β突变体能够掺入dXNTP,显示出DNA依赖性dXNA聚合酶活性。
Orthogonal nucleic acids are chemically modified nucleic acid polymers that are unable to transfer information with natural nucleic acids and thus can be used in synthetic biology to store and transfer genetic information independently. Recently, it was proposed that xylose‐DNA (dXNA) can be considered to be a potential candidate for an orthogonal system. Herein, we present the structure in solution and conformational analysis of two self‐complementary, fully modified dXNA oligonucleotides, as determined by CD and NMR spectroscopy. These studies are the initial experimental proof of the structural orthogonality of dXNAs. In aqueous solution, dXNA duplexes predominantly form a linear ladderlike (type‐1) structure. This is the first example of a furanose nucleic acid that adopts a ladderlike structure. In the presence of salt, an equilibrium exists between two types of duplex form. The corresponding nucleoside triphosphates (dXNTPs) were synthesized and evaluated for their ability to be incorporated into a growing DNA chain by using several natural and mutant DNA polymerases. Despite the structural orthogonality of dXNA, DNA polymerase β mutant is able to incorporate the dXNTPs, showing DNA‐dependent dXNA polymerase activity.
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