Real Time in Vitro Regulation of DNA Methylation Using a 5-Fluorouracil Conjugated DNA-Based Stimuli-Responsive Platform
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- 作者：Xiuhai Mao ; Ming Wei ; Chengfeng Zhu ; Jianxin Lu ; Jimin Gao ; Anna J. Simon ; Jiye Shi ; Qing Huang ; Chunhai Fan
- 刊名：ACS Applied Materials & Interfaces
- 出版年：2013
- 出版时间：April 10, 2013
- 年：2013
- 卷：5
- 期：7
- 页码：2604-2609
- 全文大小：347K
- 年卷期：v.5,no.7(April 10, 2013)
- ISSN：1944-8252
文摘
DNA methylation, catalyzed by methylases, plays a critical role in many biological processes, and many methylases have been regarded as promising targets for antimicrobial drugs. In this work, we report a stimulus responsive, self-regulating anticancer drug release platform, comprising a multifunctional DNA that upon methylation by methyltransferase (MTase) releases 5-fluorouracil (5-Fu) and in turn inhibits subsequent expression of MTase. The multifunctional DNA with anticancer drug are first methylated by DNA adenine methylation (DAM) methyltransferase (MTase) and then cut by the methylation-sensitive restriction endonuclease Dpn I. Removal of duplex from the functional DNA by the methylation/cleavage process will release the anticancer drug, resulting in inhibition of the activity of DAM in turn. Consequently, the enzyme activity of DAM MTase can be self-regulated. Furthermore, we found that the inhibition efficiency of 5-Fu significantly increase as it is functionalized with DNA.