A DNA as a Substrate and an Enzyme: Direct Profiling of Methyltransferase Activity by Cytosine Methylation of a DNAzyme

Chemistry : a European Journal
Wang LiJuewen Liu

Abstract

Inhibiting DNA methyltransferase (MTase) activity is crucial for cancer treatment. Evaluating drug candidates as inhibitors of MTase requires the measurement of its activity. However, direct profiling of MTase activity remains an analytical challenge, since a complicated hydrolysis step using methylation-sensitive restriction enzymes (msRE) was inevitable in almost all previously reported methods. Taking advantage that DNA is the substrate of MTase and certain DNA sequences, known as DNAzymes, can also have enzyme-like activities, we herein developed an enzyme-free and label-free route for direct assaying MTase activity. Specifically, adding a cytosine at the meta-position of a peroxidase-mimicking DNAzyme can improve the catalytic activity of DNAzyme up to 5-fold. After methylation of the cytosine cap, the activity is further doubled. Based on these findings, direct assaying of MTase inhibitors was performed without the extra and complicated hydrolysis step. These new findings provide a helpful tool for screening drugs for cancer therapy. The idea of using the same DNA as a substrate and an enzyme could be a general way for assaying other enzymes.

References

Feb 13, 1986·Nature·F H Westheimer
Sep 30, 1998·Chemistry & Biology·P TravascioD Sen
Jan 22, 2002·Journal of Molecular Biology·A R Feldman, D Sen
May 24, 2008·Chemical Society Reviews·Itamar WillnerBilha Willner
Mar 24, 2009·Chemical Reviews·Juewen LiuYi Lu
Jan 26, 2010·The Analyst·De-Ming KongHan-Xi Shen
Jun 18, 2010·Analytical Chemistry·De-Ming KongHan-Xi Shen
May 18, 2011·Chemical Communications : Chem Comm·Xi ZhuGuonan Chen
Jan 19, 2012·Chemistry & Biodiversity·Ming ZhangXiang Zhou
Sep 8, 2012·Analytical Chemistry·Ling ZhuChaoyong James Yang
Mar 26, 2013·Journal of the American Chemical Society·Vineeth Thachappilly Mukundan, Anh Tuân Phan
Jan 5, 2014·Analytical Chemistry·Po-Jung Jimmy HuangJuewen Liu
Apr 29, 2015·Proceedings of the National Academy of Sciences of the United States of America·Seyed-Fakhreddin TorabiYi Lu
Oct 27, 2015·Advanced Drug Delivery Reviews·Keiko Shinjo, Yutaka Kondo
Dec 15, 2015·Journal of the American Chemical Society·Eyal GolubItamar Willner
Dec 15, 2015·Nucleic Acids Research·Wenhu ZhouJuewen Liu
Dec 18, 2015·Angewandte Chemie·Zhifa ShenYingfu Li
Jan 28, 2016·Chemistry : a European Journal·Tianjun ChangDihua Shangguan
Feb 26, 2016·Theranostics·Wan Jun PohZhiqiang Gao
Mar 16, 2016·Analytical Chemistry·Runjhun Saran, Juewen Liu
Jun 18, 2016·Analytical and Bioanalytical Chemistry·Huimin DengZhiqiang Gao
Dec 6, 2016·Sensors·Dingran ChangYingfu Li
May 2, 2017·Current Opinion in Biotechnology·Claire E McGheeYi Lu
Jun 10, 2017·Chemical Reviews·Wenhu ZhouJuewen Liu
Jun 13, 2017·Chemical Communications : Chem Comm·Fei MaChun-Yang Zhang
Aug 15, 2017·Accounts of Chemical Research·Meng LiuYingfu Li
Nov 7, 2017·Angewandte Chemie·Yuehua GuoHuangxian Ju

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Citations

Jan 18, 2020·Chemical Communications : Chem Comm·Jiawei WangJun Zhou
Aug 1, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dehui QiuXiaobo Zhang
Jan 25, 2021·Analytica Chimica Acta·Yongjie YangJuewen Liu

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