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Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)
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Sequence-specific alkylation of DNA by pyrrole-imidazole polyamides through cooperative interaction
Gengo Kashiwazaki1, Toshikazu Bando, Hiroshi Sugiyama
1Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
Abstract:
We designed and synthesized an alkylating N-methylpyrrole (Py) -N-methylimidazole (Im) polyamide and l-(chloromethyl)-5-hydroxy-l,2-dihydro-3H benz[e]indole (seco-CBI) conjugate 1. DNA alkylating activities of conjugate 1 were evaluated by high-resolution denaturing polyacrylamide gel electrophoresis with DNA fragment containing human telomere repeat sequence. These results revealed that simultaneous treatment of the DNA fragment with conjugate 1 and Distamycin A (Dist) alkylate at the 5(')-GGTTAGGGTTA-3' sequence effectively due to cooperative interaction. Moreover, this combination has achieved 11-base-pair (bp) recognition. Thus, it is suggested that the utilization of one alkylating agent possessing long Py-Im polyamide moiety and short Py-Im polyamide partner can be an expedient way to attain the extension and precision of the recognition of DNA sequence.
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