Synthesis, physicochemical properties, and hydrogen bonding of 4(5)-substituted 1-H-imidazole-2-carboxamide, a potential universal reader for DNA sequencing by recognition tunneling.
Synthesis, physicochemical properties, and hydrogen bonding of 4(5)-substituted 1-H-imidazole-2-carboxamide, a potential universal reader for DNA sequencing by recognition tunneling.
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DOI：
10.1002/chem.201103306
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发表时间：
2012-05-07
影响因子：
4.3
通讯作者：
Zhang, Peiming
中科院分区：
文献类型：
--
作者：
Liang, Feng;Li, Shengqing;Lindsay, Stuart;Zhang, Peiming
我们已经开发了一种化学试剂，可以识别所有天然存在的DNA碱基，即所谓的通用阅读器，用于通过纳米孔中的识别隧道进行DNA测序。这种类型的分子的主要要求是能够与单个DNA碱基形成非共价复合物，并在电偏压下产生可识别的电子签名。1-H-咪唑-2-甲酰胺被设计为这样的识别部分，通过氢键与DNA碱基相互作用。在本研究中，我们首先提供了一种合成路线，1-H-咪唑-2-甲酰胺在其4（5）位含有一个短的ω-官能化的烷基链，其连接到金属和碳电极。然后通过UV光谱法测定咪唑-2-甲酰胺的酸解离常数。数据显示，1-H-咪唑-2-甲酰胺在pH 6-10之间以中性形式存在。密度泛函理论（DFT）和核磁共振研究表明，咪唑环存在于质子转移互变异构体中。我们提出了1-H-咪唑-2-甲酰胺互变异构的分子内机理。此外，咪唑-2-甲酰胺可以自缔合形成氢键键合的二聚体。NMR滴定发现天然核苷与1-H-咪唑-2-甲酰胺通过氢键相互作用的趋势为dG>dC → dT> dA。这些研究对于帮助我们理解在常规分析工具如NMR和FTIR不能方便地应用的纳米孔中发生的分子识别是必不可少的。
We have developed a chemical reagent that recognizes all naturally occurring DNA bases, a so called universal reader, for DNA sequencing by recognition tunnelling in nanopores. The primary requirements for this type of molecules are the ability to form non-covalent complexes with individual DNA bases and to generate recognizable electronic signatures under an electrical bias. 1-H-imidazole-2-carboxamide was designed as such a recognition moiety to interact with the DNA bases through hydrogen bonding. In the present study, we first furnished a synthetic route to 1-H-imidazole-2-carboxamide containing a short ω-functionalized alkyl chain at its 4(5) position for its attachment to metal and carbon electrodes. The acid dissociation constants of the imidazole-2-carboxamide were then determined by UV spectroscopy. The data show that the 1-H-imidazole-2-carboxamide exists in a neutral form between pH 6–10. Density functional theory (DFT) and NMR studies indicate that the imidazole ring exists in prototropic tautomers. We propose an intramolecular mechanism for tautomerization of 1-H-imidazole-2-carboxamide. In addition, the imidazole-2-carboxamide can self-associate to form hydrogen bonded dimers. NMR titration found that naturally occurring nucleosides interacted with 1-H-imidazole-2-carboxamide through hydrogen bonding in a tendency of dG>dC≫dT> dA. These studies are indispensable to assisting us in understanding the molecular recognition that takes place in the nanopore where routinely used analytical tools such as NMR and FTIR cannot be conveniently applied.
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影响因子：
10.8
作者：
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通讯作者：
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影响因子：
5.2
作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.1001831107
发表时间：
2010-09-14
影响因子：
11.1
作者：
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通讯作者：
Gundlach, Jens H.