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  • Title: Targeting specific gene by alkylating pyrrole-imidazole polyamides.
    Author: Minoshima M, Chou J, Lefebvre S, Bando T, Shinohara K, Gottesfeld JM, Sugiyama H.
    Journal: Nucleic Acids Symp Ser (Oxf); 2008; (52):363-4. PubMed ID: 18776404.
    Abstract:
    Targeting specific genes or gene products by small molecules is novel approach of cancer chemotherapy. We have developed sequence-specific DNA alkylating agents, conjugates between pyrrole (Py)-imidazole (Im) polyamides and 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H benz[e]indole (seco-CBI) with an indole linker. These compounds efficiently alkylate DNA at a targeted sequence and inhibit gene expression caused by alkylation at template strand of coding region. Recently, histone H4c gene could be targeted by polyamide-chlorambucil (Chl) conjugates. Thus, we designed and synthesized polyamide seco-CBI conjugates 1-5 targeting histone H4c coding sequence. High resolution denaturing polyacrylamide gel electrophoresis (PAGE) showed polyamide seco-CBI conjugates alkylated at the histone H4c coding sequence.
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