Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B2 to Duplex DNA.
Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B2 to Duplex DNA.
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DOI：
10.1002/chem.201600950
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Tingting Zou;S. Kizaki;G. Pandian;H. Sugiyama
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文献类型：
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作者：
Tingting Zou;S. Kizaki;G. Pandian;H. Sugiyama
为了评价抗肿瘤药物在核小体结构中的反应性，我们进行了体外研究，利用测序凝胶电泳法评估了核小体与核心区和连接区DNA的烷基化水平。我们的结果表明，与裸露DNA相比，在核心DNA中，双卡霉素B2的烷基化效率显著降低，而在无组蛋白连接的DNA位点上，其烷基化效率显著增加。我们发现，核小体组装改变了双链DNA对多卡霉素B2的可及性，这可能会促进其作为抗肿瘤药物的设计。
To evaluate the reactivity of antitumor agents in a nucleosome architecture, we conducted in vitro studies to assess the alkylation level of duocarmycin B2 on nucleosomes with core and linker DNA using sequencing gel electrophoresis. Our results suggested that the alkylating efficiencies of duocarmycin B2 were significantly decreased in core DNA and increased at the histone-free linker DNA sites when compared with naked DNA conditions. Our finding that nucleosome assembly alters the accessibility of duocarmycin B2 to duplex DNA could advance its design as an antitumor agent.