Highly Cooperative DNA Dialkylation by the Homodimer of Imidazole−Pyrrole Diamide−CPI Conjugate with Vinyl Linker
Highly Cooperative DNA Dialkylation by the Homodimer of Imidazole−Pyrrole Diamide−CPI Conjugate with Vinyl Linker
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咪唑-吡咯二酰胺-CPI 缀合物与乙烯基连接体的同二聚体的高度协同 DNA 二烷基化
DOI：
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发表时间：
2000
期刊：
影响因子：
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通讯作者：
H. Sugiyama
中科院分区：
文献类型：
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作者：
Z. Tao;I. Saito;H. Sugiyama
我们合成了新型的具有乙烯基连接基的二酰胺-CPI缀合物7。用高分辨变性凝胶电泳法研究了7对双链DNA的序列选择性烷基化作用。高效的烷基化主要在两条链上的5 '-PyG（A/T）CPu-3'位点的嘌呤处同时发生，浓度为7纳摩尔。这些结果表明，根据Dervan配对规则，缀合物7的同二聚体使两条链二烷基化，以及一种新的识别模式，其中Im-乙烯基接头（L）对靶向G/C碱基对。除了主要的二烷基化位点外，还在5 '-GT（A/T）GC-3'处观察到次要的烷基化位点。这种烷基化可以用类似的滑动同二聚体识别模式来解释，其中L-L对识别A/T碱基对。使用寡核苷酸（ODNs）进一步证实了7的同源二聚体的有效二烷基化。HPLC分析表明，缀合物7同时烷基化GN 3.
We synthesized new type of diamide−CPI conjugate possessing a vinyl linker, 7. Sequence-selective alkylation of double-stranded DNA by 7 was investigated by high-resolution denaturing gel electrophoresis using ∼400 bp DNA fragments. Highly efficient alkylation predominantly occurs simultaneously at the purines of 5‘-PyG(A/T)CPu-3‘ site on both strands at a nanomolar concentration of 7. These results suggest that the homodimer of conjugate 7 dialkylates both strands according to Dervan's pairing rule together with a new mode of recognition in which the Im-vinyl linker (L) pair targets G/C base pairs. In addition to the major dialkylation sites, a minor alkylation site was also observed at 5‘-GT(A/T)GC-3‘. This alkylation can be explained by an analogous slipped homodimer recognition mode in which the L−L pair recognizes the A/T base pair. Efficient dialkylation by the homodimer of 7 was further confirmed using oligonucleotides (ODNs). HPLC analysis revealed that the conjugate 7 simultaneously alkylates GN3...