Binding site size limit of the 2:1 pyrrole-imidazole polyamide-DNA motif

Binding site size limit of the 2:1 pyrrole-imidazole polyamide-DNA motif
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DOI:
10.1073/pnas.93.14.6981
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发表时间:
1996-07-09
影响因子:
11.1
通讯作者:
Dervan, PB
Dervan, PB
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kelly, JJ;Baird, EE;Dervan, PB

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含有N-甲基咪唑(Im)和N-甲基吡咯(Py)氨基酸的聚酰胺可以以反平行并排二聚复合物的形式结合,用于DNA小沟中的序列特异性识别。六种含有三至八个环的聚酰胺分别结合长度为5-10 bp的DNA位点。定量DNA酶I足迹滴定实验表明,亲和力最大化,并在五,六,和七个环的大小是相似的。序列特异性随着聚酰胺的长度增加超过5个环而降低。这些结果为设计新的聚酰胺提供了有用的指导,这些聚酰胺结合更长的DNA位点,具有增强的亲和力和特异性。
Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids can be combined in antiparallel side-by-side dimeric complexes for sequence-specific recognition in the minor groove of DNA. Six polyamides containing three to eight rings bind DNA sites 5-10 bp in length, respectively. Quantitative DNase I footprint titration experiments demonstrate that affinity maximizes and is similar at ring sizes of five, six, and seven. Sequence specificity decreases as the length of the polyamides increases beyond five rings. These results provide useful guidelines for the design of new polyamides that bind longer DNA sites with enhanced affinity and specificity.