Binding of hairpin pyrrole and imidazole polyamides to DNA: relationship between torsion angle and association rate constants.
Binding of hairpin pyrrole and imidazole polyamides to DNA: relationship between torsion angle and association rate constants.
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DOI：
10.1093/nar/gks897
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发表时间：
2012-12
影响因子：
14.9
通讯作者：
Sugiyama H
中科院分区：
文献类型：
--
作者：
Han YW;Matsumoto T;Yokota H;Kashiwazaki G;Morinaga H;Hashiya K;Bando T;Harada Y;Sugiyama H
N-甲基吡咯（Py）-N-甲基咪唑（Im）聚酰胺是一种有机小分子，可与DNA序列特异性结合，并可用作合成的DNA结合配体。本研究合成了五种不同Im环数的发夹型八环Py-Im聚酰胺1-5，并利用表面等离子体共振技术研究了它们的结合行为。发现Py-Im聚酰胺与其靶DNA的结合率（ka）随着Py-Im聚酰胺中Im的数量而降低。由密度泛函理论计算得到的四元环Py-Im聚酰胺的结构表明，Py酰胺羰基的二面角为14 ° ~ 18°，而Im的二面角明显较小.由于DNA的小沟具有螺旋结构，平面Py-Im聚酰胺需要改变它们的构象以在结合到小沟时适合它。数据解释了由Im的掺入引起的Py-Im聚酰胺的平面性的增加降低了Py-Im聚酰胺的缔合速率。Py-Im聚酰胺与DNA结合的基本知识将有助于设计发夹Py-Im聚酰胺作为合成的DNA结合模块。
N-methylpyrrole (Py)-N-methylimidazole (Im) polyamides are small organic molecules that bind to DNA with sequence specificity and can be used as synthetic DNA-binding ligands. In this study, five hairpin eight-ring Py–Im polyamides 1–5 with different number of Im rings were synthesized, and their binding behaviour was investigated with surface plasmon resonance assay. It was found that association rate (ka) of the Py–Im polyamides with their target DNA decreased with the number of Im in the Py–Im polyamides. The structures of four-ring Py–Im polyamides derived from density functional theory revealed that the dihedral angle of the Py amide carbonyl is 14∼18°, whereas that of the Im is significantly smaller. As the minor groove of DNA has a helical structure, planar Py–Im polyamides need to change their conformation to fit it upon binding to the minor groove. The data explain that an increase in planarity of Py–Im polyamide induced by the incorporation of Im reduces the association rate of Py–Im polyamides. This fundamental knowledge of the binding of Py–Im polyamides to DNA will facilitate the design of hairpin Py–Im polyamides as synthetic DNA-binding modules.
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影响因子：
2.9
作者：
Baliga, R;Baird, EE;Crothers, DM
通讯作者：
Crothers, DM
影响因子：
2.1
作者：
Kyo, M;Yamamoto, T;Yamamoto, M
通讯作者：
Yamamoto, M
影响因子：
15
作者：
Arora, PS;Ansari, AZ;Dervan, PB
通讯作者：
Dervan, PB
影响因子：
64.8
作者：
Trauger, JW;Baird, EE;Dervan, PB
通讯作者：
Dervan, PB
影响因子：
15
作者：
Fechter, EJ;Dervan, PB
通讯作者：
Dervan, PB