Molecular design of DNA alkylating pyrrole-imidazole polyamides with longer recognition sequence
Author(s) -
Masafumi Minoshima,
Shunta Sasaki,
Kenichi Shinohara,
Tatsuhiko Shimizu,
Toshikazu Bando,
Hiroshi Sugiyama
Publication year - 2006
Publication title -
nucleic acids symposium series
Language(s) - English
Resource type - Journals
eISSN - 1746-8272
pISSN - 0261-3166
DOI - 10.1093/nass/nrl082
Subject(s) - dna , alkylation , indole test , linker , sequence (biology) , chemistry , pyrrole , polyamide , base pair , recognition sequence , imidazole , stereochemistry , biochemistry , polymer chemistry , organic chemistry , restriction enzyme , computer science , catalysis , operating system
The sequence-specificity, and DNA alkylating activity of the conjugate 1, which consists of N-methylpyrrole (Py)-N-methylimidazole (Im) polyamides, 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) with indole linker, were investigated in the absence or presence of partner Py-Im polyamide 2. High-resolution denaturing polyacrylamide gel electrophoresis showed that the specificity of DNA alkylation by 1 modulated in the presence of partner 2. We found that sequence-specific DNA alkylation by 1 and 2 with 10 base pair (bp) match recognition sequence through heterodimer formation. This result indicates one possibility of DNA alkylation with longer recognition sequence by different two molecules.
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