Metabolic-Pathway-Oriented Screening Targeting S-Adenosyl-L-methionine Reveals the Epigenetic Remodeling Activities of Naturally Occurring Catechols
Metabolic-Pathway-Oriented Screening Targeting S-Adenosyl-L-methionine Reveals the Epigenetic Remodeling Activities of Naturally Occurring Catechols
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DOI：
10.1021/jacs.9b08698
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发表时间：
2020-01-08
影响因子：
15
通讯作者：
Urano, Yasuteru
中科院分区：
文献类型：
--
作者：
Ogihara, Shusuke;Komatsu, Toru;Urano, Yasuteru
甲基转移反应在许多生物学现象中起着重要的作用，其中甲基化辅因子S-腺苷-L-甲硫氨酸（SAM）是协调这些反应的重要媒介。我们已经开发了一种基于荧光探针的高通量筛选（HTS）系统来寻找控制细胞SAM水平的化合物。HTS与药物重新定位库揭示了儿茶酚-O-甲基转移酶（COMT）及其底物在控制结直肠肿瘤细胞中SAM浓度和组蛋白甲基化水平中的重要性。
Methyl transfer reactions play important roles in many biological phenomena, wherein the methylation cofactor S-adenosyl-L-methionine (SAM) serves as the important currency to orchestrate those reactions. We have developed a fluorescent-probe-based high-throughput screening (HTS) system to search for the compounds that control cellular SAM levels. HTS with a drug repositioning library revealed the importance of catechol-O-methyltransferase (COMT) and its substrates in controlling the SAM concentrations and histone methylation levels in colorectal tumor cells.