ArticleChemMedChem2025
Efficacy of DNA Intercalator-Conjugated Triplex-Forming Oligonucleotide as Anticancer Agent.
Article in ChemMedChem, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
A triplex-forming oligonucleotide (TFO) can form a sequence-specific triple helix via Hoogsteen hydrogen bonding to polypurine tracts within a major groove side of a DNA duplex. Triplex formation can induce a double-strand break, and this phenomenon at the amplified gene loci can selectively induce the cell death of cancer cells with specific gene amplification. However, the relationship between the binding affinity of TFO for target gene loci and the cell death response remains unclear. In this study, it is aimed to develop DNA intercalator-conjugated TFOs with higher affinity for the human epidermal growth factor receptor type2 gene, which is often amplified in breast cancer cells, than the unmodified TFO. The binding affinity of the TFOs for the target DNA duplex is analyzed using nondenaturing polyacrylamide gel electrophoresis, and one of the DNA intercalator-conjugated TFOs show a higher binding affinity for the target duplex than the unmodified TFO. The cell death responses induced by these TFOs using the WST-8 assay is also evaluated suggesting that the higher binding affinity of the TFO for amplified gene loci can lead to a stronger cell death response of cancer cells with specific gene amplification.
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