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  • Title: Sequence-specific alkylation by a tandem motif of pyrrole-imidazole CBI conjugate.
    Author: Sasaki S, Minoshima M, Fujimoto J, Shinohara K, Bando T, Sugiyama H.
    Journal: Nucleic Acids Symp Ser (Oxf); 2007; (51):265-6. PubMed ID: 18029688.
    Abstract:
    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.
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