Programmable oligomers for minor groove DNA recognition
Programmable oligomers for minor groove DNA recognition
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DOI：
10.1021/ja0621795
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发表时间：
2006-07-19
影响因子：
15
通讯作者：
Dervan, Peter B.
中科院分区：
文献类型：
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作者：
Doss, Raymond M.;Marques, Michael A.;Dervan, Peter B.
通过将咪唑(Im)、吡咯(Py)和羟基吡咯(Hp)这三个五元芳香胺并排配对，可以在小凹槽中区分DNA的四个Watson-Crick碱基对，四种不同的方法。基于芳环对边不对称的小槽识别模式，第二代杂环对咪唑并吡啶/吡咯(Ip/Py)和羟基苯并咪唑/吡咯(Hz/Py)揭示了可以实现不基于地塞米松类似物的识别元件。一组新的端帽杂环二聚体，恶唑-羟基苯并咪唑(No-HZ)和氯噻吩羟基苯并咪唑(Ct-HZ)，与Py-Py配对，可以高亲和力和选择性地结合DNA的小沟槽中的连续碱基对，特别是5‘-GT-3’和5‘-TT-3’。利用这一技术，我们开发了一类不再基于地沙霉素的N-甲基吡咯甲酰胺的序列特异性DNA细沟识别的新的寡聚体。
The four Watson-Crick base pairs of DNA can be distinguished in the minor groove by pairing side-by-side three five-membered aromatic carboxamides, imidazole (Im), pyrrole (Py), and hydroxypyrrole (Hp), four different ways. On the basis of the paradigm of unsymmetrical paired edges of aromatic rings for minor groove recognition, a second generation set of heterocycle pairs, imidazopyridine/pyrrole (Ip/Py) and hydroxybenzimidazole/pyrrole (Hz/Py), revealed that recognition elements not based on analogues of distamycin could be realized. A new set of end-cap heterocycle dimers, oxazole-hydroxybenzimidazole (No-Hz) and chlorothiophene-hydroxybenzimidazole (Ct-Hz), paired with Py-Py are shown to bind contiguous base pairs of DNA in the minor groove, specifically 5'-GT-3' and 5'-TT-3', with high affinity and selectivity. Utilizing this technology, we have developed a new class of oligomers for sequence-specific DNA minor groove recognition no longer based on the N-methyl pyrrole carboxamides of distamycin.