Development of chemical biological tools to monitor and control pathologically important methyltransferase activites
Project/Area Number |
15K14937
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Physical pharmacy
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Research Institution | The University of Tokyo |
Principal Investigator |
Komatsu Toru 東京大学, 大学院薬学系研究科(薬学部), 助教 (40599172)
|
Project Period (FY) |
2015-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | ケミカルバイオロジー / 創薬化学 / 酵素 / 生化学 |
Outline of Final Research Achievements |
Methyl transfer reactions play important roles in many biological phenomena, and the methylation cofactor S-adenosyl-L-methionine (SAM) serves as the important currency to govern those reactions inside cells. We have developed a fluorescent probe-based system to detect this important cofactor by fluorescence activation upon coupled reaction with protein L-isoaspartyl methyltransferase (PIMT). By carefully optimizing the molecular structures, the system was established as highly sensitive off-on or ratiometric type responsive platform that can quantify the cofactor as low as 20 nM within 10 min with mix-and-read platform. The system was applied (1) to detect the changes of cellular methylation potential at altered cellular conditions, and (2) to monitor general lysine methyltransferase reactions for inhibitor screening.
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Report
(3 results)
Research Products
(57 results)
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[Journal Article] Discovery and Mechanistic Characterization of Selective Inhibitors of H2S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide2017
Author(s)
K. Hanaoka, K. Sasakura, Y. Suwanai, S. Toma-Fukai, K. Shimamoto, Y. Takano, N. Shibuya, T. Terai, T. Komatsu, T. Ueno, Y. Ogasawara, Y. Tsuchiya, Y. Watanabe, H. Kimura, C. Wang, M. Uchiyama, H. Kojima, T. Okabe, Y. Urano, T. Shimizu, T. Nagano
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Journal Title
Sci. Rep.
Volume: 7
Issue: 1
Pages: 40227-40227
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Development of a Reversible Fluorescent Probe for Reactive Sulfur Species, Sulfane Sulfur, and its Biological Application2017
Author(s)
Takano Y, Hanaoka K, Shimamoto K, Miyamoto R, Komatsu T, Ueno T, Terai T, Kimura H, Nagano T, Urano Y
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Journal Title
Chem Commun
Volume: 53
Issue: 6
Pages: 1064-1067
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Development of an Azoreductase-based Reporter System with Synthetic Fluorogenic Substrates2017
Author(s)
Narae Shin, Kenjiro Hanaoka, Wen Piao, Takuya Miyakawa, Tomotsumi Fujisawa, Satoshi Takeuchi, Shodai Takahashi, Toru Komatsu, Tasuku Ueno, Takuya Terai, Tahei Tahara, Masaru Tanokura, Tetsuo Nagano, Yasuteru Urano
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Journal Title
ACS Chem. Biol.
Volume: 12
Issue: 2
Pages: 558-563
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Discovery of Cell-type-specific and Disease-related Enzymatic Activity Changes via Global Evaluation of Peptide Metabolism2017
Author(s)
Jun Onagi, Toru Komatsu, Yuki Ichihashi, Yugo Kuriki, Mako Kamiya, Takuya Terai, Tasuku Ueno, Kenjiro Hanaoka, Hiroyuki Matsuzaki, Keisuke Hata, Toshiaki Watanabe, Tetsuo Nagano, and Yasuteru Urano
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Journal Title
J. Am. Chem. Soc.
Volume: 139
Issue: 9
Pages: 3465-3472
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Unexpected photo-instability of 2,6-sulfonamide-substituted BODIPYs and its application to development of caged GABA2016
Author(s)
Aoi Takeda, Toru Komatsu, Hiroshi Nomura, Naka Masamitsu, Norio Matsuki, Yuji Ikegaya, Takuya Terai, Tasuku Ueno, Kenjiro Hanaoka, Tetsuo Nagano, Yasuteru Urano
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Journal Title
ChemBioChem
Volume: 17
Issue: 13
Pages: 1-9
DOI
Related Report
Peer Reviewed
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[Journal Article] Development of Practical Red Fluorescent Probe for Cytoplasmic Calcium Ions with Greatly Improved Cell-membrane Permeability2016
Author(s)
Kazuhisa Hirabayashi, Kenjiro Hanaoka, Takahiro Egawa, Chiaki Kobayashi, Shodai Takahashi, Toru Komatsua, Tasuku Ueno, Takuya Terai, Yuji Ikegaya, Tetsuo Nagano, Yasuteru Urano
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Journal Title
Cell Calcium
Volume: 60
Issue: 4
Pages: 256-265
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Rapid and sensitive detection of early esophageal squamous cell carcinoma with fluorescence probe targeting dipeptidylpeptidase IV.2016
Author(s)
Onoyama H, Kamiya M, Kuriki Y, Komatsu T, Abe H, Tsuji Y, Yagi K, Yamagata Y, Aikou S, Nishida M, Mori K, Yamashita H, Fujishiro M, Nomura S, Shimizu N, Fukayama M, Koike K, Urano Y, Seto Y
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Journal Title
Sci Rep.
Volume: 6
Issue: 1
Pages: 26399-26399
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of Lung Inflammation-Related Elevation of Acylamino Acid Releasing Enzyme (APEH) Activity Using an Enzymomics Approach2016
Author(s)
Yoko Takano, Kenjiro Hanaoka, Kazuhito Shimamoto, Ryo Miyamoto, Toru Komatsu, Tasuku Ueno, Takuya Terai, Hideo Kimura, Tetsuo Nagano, Yasuteru Urano
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Journal Title
Chemical and Pharmaceutical Bulletin
Volume: 64
Issue: 11
Pages: 1533-1538
DOI
NAID
ISSN
0009-2363, 1347-5223
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Artificial Ligands of Streptavidin (ALiS): Discovery, Characterization, and Application for Reversible Control of Intracellular Protein Transport2015
Author(s)
Takuya Terai, Moe Kohno, Gaelle Boncompain, Shigeru Sugiyama, Nae Saito, Ryo Fujikake, Tasuku Ueno, Toru Komatsu, Kenjiro Hanaoka, Takayoshi Okabe, Yasuteru Urano, Franck Perez, and Tetsuo Nagano
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Journal Title
J. Am. Chem. Soc.
Volume: 137
Issue: 33
Pages: 10464-10467
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Identification of tissue-restricted bio-reaction suitable for in vivo targeting by fluorescent substrate library-based enzyme discovery2015
Author(s)
Kentaro Yoshioka, Toru Komatsu, Akihiro Nakada, Jun Onagi, Yugo Kuriki, Mitsuyasu Kawaguchi, Takuya Terai, Tasuku Ueno, Kenjiro Hanaoka, Tetsuo Nagano, and Yasuteru Urano
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Journal Title
J. Am. Chem. Soc.
Volume: 137
Issue: 38
Pages: 12187-12190
DOI
Related Report
Peer Reviewed
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