DNA site-specific N3-adenine methylation targeted to estrogen receptor-positive cells.

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Kishton RJ, Miller SE, Perry H, Lynch T, Patel M, Gore VK, Akkaraju GR, Varadarajan S

DNA site-specific N3-adenine methylation targeted to estrogen receptor-positive cells.

Bioorg Med Chem. 2011 Sep 1;19(17):5093-102. doi: 10.1016/j.bmc.2011.07.026. Epub 2011 Jul 22.

PubMed ID
21839641 [ View in PubMed
]
Abstract

A compound that can target cells expressing the estrogen receptor (ER), and produce predominantly 3-MeA adducts in those cells has been designed and synthesized. This compound produces mainly the 3-MeA adduct upon reaction with calf thymus DNA, and binds to the ER with a relative binding affinity of 51% (estradiol = 100%). The compound is toxic to ER-expressing MCF-7 breast cancer cells, and pre-treatment with the ER antagonist fulvestrant abrogates the toxicity. Pre-treatment of MCF-7 cells with netropsin, which inhibits N3-adenine methylation by the compound, resulted in a threefold decrease in the toxicity. These results demonstrate the feasibility of this strategy for producing 3-MeA adducts in targeted cells.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
EstradiolEstrogen receptor alphaIC 50 (nM)0.57N/AN/ADetails