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Molecular design of hairpin pyrrole-imidazole polyamides possessing sequence specific DNA alkylating moiety
Akihiko Narita1, Toshikazu Bando, Hiroshi Sugiyama
1School of Biomedical Science, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Abstract:
By conjugating pyrrole (Py)/imidazole (Im) hairpin polyamides with CBI, a stable alkylating moiety, we have developed a new type of DNA-sequence-specific alkylating agent. The sequence specificity and alkylation efficiency of the CBI conjugates were analyzed with high-resolution denaturing gel electrophoresis using linear 450- and 1000-bp DNA. The results demonstrate that CBI conjugates selectively alkylate adenine in specific sequences, whereas the previous type of alkylating polyamide, which contains segment A of DU-86, alkylates both adenine and guanine.
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