Molecular design of DNA alkylating pyrrole-imidazole polyamides with longer recognition sequence.
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.
Minoshima
Masafumi
M
Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo, Kyoto 606-8502, Japan.
Sasaki
Shunta
S
Shinohara
Ken-ichi
K
Shimizu
Tatsuhiko
T
Bando
Toshikazu
T
Sugiyama
Hiroshi
H
D000477:Alkylating Agents / Q000737:chemistry*; D000478:Alkylation; D020029:Base Pairing; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D011758:Pyrroles / Q000737:chemistry*
D000477:Alkylating Agents; D011758:Pyrroles; D004247:DNA