Specific molecular recognition of mixed nucleic acid sequences: An aromatic dication that binds in the DNA minor groove as a dimer
Specific molecular recognition of mixed nucleic acid sequences: An aromatic dication that binds in the DNA minor groove as a dimer
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DOI：
10.1073/pnas.97.1.12
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发表时间：
2000-01-04
影响因子：
11.1
通讯作者：
Wilson, WD
中科院分区：
文献类型：
--
作者：
Wang, L;Bailly, C;Wilson, WD
通过呋喃环连接的苯脒阳离子基团（呋喃脒）和相关化合物作为单体与DNA的AT序列结合。通过定量足迹分析发现，呋喃脒的苯环之一被苯并咪唑取代的不对称衍生物（DB 293）与DNA上含CC的位点的结合比与纯AT序列的结合更强。NMR结构分析和表面等离子体共振结合结果清楚地表明，DB293结合在小沟在特定的CC-含有序列的DNA在一个高度合作的方式作为一个堆叠的二聚体。DB293的对称双苯基或双苯并咪唑类似物均不显著结合含CC的序列。DB293为设计特异性识别混合DNA序列的化合物提供了范例，并扩展了小分子DNA识别的边界。
Phenylamidine cationic groups linked by a furan ring (furamidine) and related compounds bind as monomers to AT sequences of DNA. An unsymmetric derivative (DB293) with one of the phenyl rings of furamidine replaced with a benzimidazole has been found by quantitative footprinting analyses to bind to CC-containing sites on DNA more strongly than to pure AT sequences. NMR structural analysis and surface plasmon resonance binding results clearly demonstrate that DB293 binds in the minor groove at specific CC-containing sequences of DNA in a highly cooperative manner as a stacked dimer. Neither the symmetric bisphenyl nor bisbenzimidazole analogs of DB293 bind significantly to the CC containing sequences. DB293 provides a paradigm for design of compounds for specific recognition of mixed DNA sequences and extends the boundaries for small molecule-DNA recognition.