ArticleNucleic acids research2006
Alkylation of template strand of coding region causes effective gene silencing.
Article in Nucleic acids research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Novel therapeutic strategy targeting STMN1 using chlorambucil-conjugated pyrrole-imidazole polyamide in small cell lung cancer.International journal of cancer · 2026Article
- Targeting the mutant PIK3CA gene by DNA-alkylating pyrrole-imidazole polyamide in cervical cancer.Cancer science · 2021Article
- Targeting anaplastic lymphoma kinase (ALK) gene alterations in neuroblastoma by using alkylating pyrrole-imidazole polyamides.PloS one · 2021Article
- Review
- Deciphering the genomic targets of alkylating polyamide conjugates using high-throughput sequencing.Nucleic acids research · 2016Article
- Chromatin structure determines accessibility of a hairpin polyamide-chlorambucil conjugate at histone H4 genes in pancreatic cancer cells.Bioorganic & medicinal chemistry letters · 2012Article
- Small molecules targeting histone H4 as potential therapeutics for chronic myelogenous leukemia.Molecular cancer therapeutics · 2008Article
- Unanticipated differences between alpha- and gamma-diaminobutyric acid-linked hairpin polyamide-alkylator conjugates.Nucleic acids research · 2007Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We recently developed a new type of pyrrole (Py)-imidazole (Im) polyamide-tetrahydrocyclopropabenzindolone (CBI) conjugate with an indole linker as a stable sequence-specific alkylating agent. In this study, we investigated the gene silencing activities of polyamides A, B and C, which selectively alkylate specific sequences in the promoter region, non-coding strand and coding strand, respectively, of the green fluorescent protein (GFP) gene. GFP vectors were transfected into human colon carcinoma cells (HCT116), and the cells were treated with 100 nM of the polyamides for 24 h. Fluorescence microscopy indicated that a significant reduction of GFP fluorescence was only observed in the cells that were treated with polyamide C. In clear contrast, polyamides A and B did not show such activity. Moreover, real-time PCR demonstrated selective reduction of the expression of GFP mRNA following treatment with polyamide C. These results suggest that alkylating Py-Im polyamides that target the coding strand represent a novel approach for sequence-specific gene silencing.
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Registered trials
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