Metabolic-Pathway-Oriented Screening Targeting S‑Adenosyl‑l‑methionine Reveals the Epigenetic Remodeling Activities of Naturally Occurring Catechols

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 fo...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2020-01, Vol.142 (1), p.21-26
Main Authors: Ogihara, Shusuke, Komatsu, Toru, Itoh, Yukihiro, Miyake, Yuka, Suzuki, Takayoshi, Yanagi, Kouichi, Kimura, Yusuke, Ueno, Tasuku, Hanaoka, Kenjiro, Kojima, Hirotatsu, Okabe, Takayoshi, Nagano, Tetsuo, Urano, Yasuteru
Format: Article
Language:English
Subjects:
Animals
Catechol O-Methyltransferase - metabolism
Catechols - pharmacology
Epigenesis, Genetic
HT29 Cells
Humans
Metabolic Networks and Pathways
Mice
Mice, Inbred BALB C
Mice, Nude
S-Adenosylmethionine - metabolism
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Summary: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.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.9b08698