High Fidelity of Base Pairing by 2-Selenothymidine in DNA
High Fidelity of Base Pairing by 2-Selenothymidine in DNA
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DOI：
10.1021/ja909330m
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发表时间：
2010-02-24
影响因子：
15
通讯作者：
Huang, Zhen
中科院分区：
文献类型：
--
作者：
Hassan, Abdalla E. A.;Sheng, Jia;Huang, Zhen
碱基对是核酸序列依赖性识别、遗传信息存储和 DNA 聚合酶复制高保真度的贡献者。然而，摆动碱基配对（其中 T 与 G 而不是 A 配对）降低了特定碱基配对识别并损害了酶促聚合的高保真度。通过胸苷2位的硒原子探测，我们通过操纵2位外位的空间和电子效应来研究摆动辨别，提供了一种独特的化学策略来增强碱基对特异性。我们在这里报告了新型 2-Se-胸苷 (T-Se) 衍生物、其亚磷酰胺和 Sc-DNA 的首次合成。我们对 2-Se-T DNA 的生物物理和结构研究表明，具有弱氢键能力的大体积 2-Se 原子可以在很大程度上增加错配歧视（包括 T/G 摆动和 T/C 错配碱基对），同时保持 T-Se/A 与天然 T/A 碱基对几乎相同。 2-Se原子体积和电子效应可能是导致摆动T-Se/G碱基对形成的主要因素。我们的研究提供了一种潜在的新工具来研究碱基对的特异性识别，这是复制、转录和翻译过程中高保真度的基础。此外，这种硒原子特异性取代和探测可用于核酸的 X 射线晶体结构和功能研究。
The base pairs are the contributors to the sequence-dependent recognition of nucleic acids, genetic information storage, and high fidelity of DNA polymerase replication. However, the wobble base pairing, Where T pairs with G instead of A. reduces specific base-pairing recognition and compromises the high fidelity of the enzymatic polymerization. Via the selenium atomic probing at the 2-position of thymidine, we have investigated the wobble discrimination by manipulating the steric and electronic effects at the 2-exo position, providing a unique chemical strategy to enhance the base pair specificity. We report here the first synthesis of the novel 2-Se-thymidine (T-Se) derivative, its phosphoramidite, and the Sc-DNAs. Our biophysical and structural studies of the 2-Se-T DNAs reveal that the bulky 2-Se atom with a weak hydrogen-bonding ability can largely increase mismatch discriminations (including T/G wobble and T/C mismatched base pairs) while maintaining the T-Se/A virtually identical to the native T/A base pair. The 2-Se atom bulkiness and the electronic effect are probably the main factors responsible for the discrimination against the formation of the wobble T-Se/G base pair. Our investigations provide a potential novel tool to investigate the specific recognition of base pairs, which is the basis of high fidelity during replication, transcription, and translation. Furthermore, this Se-atom-specific substitution and probing are useful for X-ray crystal structure and function studies of nucleic acids.