Sequence-specific alkylation by a tandem motif of pyrrole-imidazole CBI conjugate

We have developed various types of sequence-specific alkylating agents by conjugation of Py-Im polyamides and alkylating moieties 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) with an indole linker. In order to extend the length of target DNA sequence of the hairpin Py-Im polyam...

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Bibliographic Details
Published in:Nucleic Acids Symposium Series 2007-11, Vol.51 (1), p.265-266
Main Authors: Sasaki, Shunta, Minoshima, Masafumi, Fujimoto, Jun, Shinohara, Ken-ichi, Bando, Toshikazu, Sugiyama, Hiroshi
Format: Article
Language:English
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Summary:We have developed various types of sequence-specific alkylating agents by conjugation of Py-Im polyamides and alkylating moieties 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) with an indole linker. In order to extend the length of target DNA sequence of the hairpin Py-Im polyamide 1, we designed and synthesized Y-shaped and tandem hairpin Py-Im polyamides 2 and 3. High-resolution denaturing polyacrylamide gel electrophoresis using 5'-Texas Red-labeled 465-bp DNA fragments revealed that conjugates 2 and 3 alkylated the adenine of target DNA sequences at nanomolar concentrations. Furthermore, evaluation in human cancer cell lines revealed that these Py-Im polyamides 2 and 3 have strong cytotoxicities.
ISSN:0261-3166
1746-8272
DOI:10.1093/nass/nrm133