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

被引:92
作者
Kelly, JJ [1 ]
Baird, EE [1 ]
Dervan, PB [1 ]
机构
[1] CALTECH,DIV CHEM & CHEM ENGN,PASADENA,CA 91125
关键词
D O I
10.1073/pnas.93.14.6981
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页码:6981 / 6985
页数:5
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