The effect of minor-groove hydrogen-bond acceptors and donors on the stability and replication of four unnatural base pairs
The effect of minor-groove hydrogen-bond acceptors and donors on the stability and replication of four unnatural base pairs
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DOI：
10.1021/ja034099w
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发表时间：
2003-05-21
影响因子：
15
通讯作者：
Romesberg, FE
中科院分区：
文献类型：
--
作者：
Matsuda, S;Henry, AA;Romesberg, FE
本文报道了在含有苯并呋喃、苯并噻吩、吲哚和苯并三唑核碱基的非天然核苷酸之间形成的含有自对的DNA的稳定性和复制。这些核碱基类似物基于相似的支架，但具有不同的氢键供体/受体基团，预计在双小槽中取向。非自然碱基对似乎不会引起主要的结构扭曲，并在b型双相的约束下被容纳。这些非自然碱基对之间的差异仅体现在聚合酶介导的延伸步骤中，而不是在碱基对稳定性或合成方面。苯并三唑自偶扩展的效率仅比正确的天然碱基对低200倍。这些数据在可用的聚合酶晶体结构方面进行了讨论，并暗示进一步的修饰可能导致可以有效地合成和扩展的非自然碱基对，从而扩大遗传字母表。
The stability and replication of DNA containing self-pairs formed between unnatural nucleotides bearing benzofuran, benzothiophene, indole, and benzotriazole nucleobases are reported. These nucleobase analogues are based on a similar scaffold but have different hydrogen-bond donor/acceptor groups that are expected to be oriented in the duplex minor groove. The unnatural base pairs do not appear to induce major structural distortions and are accommodated within the constraints of a B-form duplex. The differences between these unnatural base pairs are manifest only in the polymerase-mediated extension step, not in base-pair stability or synthesis. The benzotriazole self-pair is extended with an efficiency that is only 200-fold less than a correct natural base pair. The data are discussed in terms of available polymerase crystal structures and imply that further modifications may result in unnatural base pairs that can be both efficiently synthesized and extended, resulting in an expanded genetic alphabet.