Efforts toward the expansion of the genetic alphabet: Information storage and replication with unnatural hydrophobic base pairs
Efforts toward the expansion of the genetic alphabet: Information storage and replication with unnatural hydrophobic base pairs
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DOI：
10.1021/ja9940064
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发表时间：
2000-04-12
影响因子：
15
通讯作者：
Romesberg, FE
中科院分区：
文献类型：
--
作者：
Ogawa, AK;Wu, YQ;Romesberg, FE
对互补核碱基之间链间氢键的忠实识别构成了遗传密码的基础。复制含有稳定第三碱基对的 DNA 的能力将允许通过用第三碱基对补充遗传字母表中现有的两个碱基对来扩展 DNA 的信息内容。我们报告了非天然核碱基的优化，其双链 DNA 中的配对基于碱基间疏水相互作用。我们表明，这种非天然碱基对的稳定性和选择性可能与天然碱基对相当，甚至超过了天然碱基对。我们还证明，大肠杆菌 DNA 聚合酶 I 的 Klenow 片段将几个非天然碱基对整合到 DNA 中，其效率与天然 DNA 合成的效率相当。此外，非天然碱基与天然碱基正交，正确配对相对于错误配对至少有一个数量级的优势。
The faithful recognition of the interstrand hydrogen bonds between complementary nucleobases forms the foundation of the genetic code. The ability to replicate DNA containing a stable third base pair would allow for an expansion of the information content of DNA by supplementing the existing two base pairs of the genetic alphabet with a third. We report the optimization of unnatural nucleobases whose pairing in duplex DNA is based on interbase hydrophobic interactions. We show that the stability and selectivity of such unnatural base pairs may be comparable to, or even exceed, that of native pairs. We also demonstrate that several unnatural base pairs are incorporated into DNA by Klenow fragment of Escherichia coli DNA polymerase I with an efficiency equivalent to that of native DNA synthesis. Moreover, the unnatural bases are orthogonal to the native bases, with correct pairing being favored by at least an order of magnitude relative to mispairing.