Development of highly sensitive chemical detection of the nucleic acid methylations strongly affecting lifestyle diseases

• Project/Area Number: 15H02190
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Okamoto Akimitsu 東京大学, 先端科学技術研究センター, 教授 (60314233)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥42,770,000 (Direct Cost: ¥32,900,000、Indirect Cost: ¥9,870,000); Fiscal Year 2017: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000); Fiscal Year 2016: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000); Fiscal Year 2015: ¥21,190,000 (Direct Cost: ¥16,300,000、Indirect Cost: ¥4,890,000)
• Keywords: DNA / メチル化 / 脱メチル化 / ヒストン / 金属反応 / ペプチド合成 / エピジェネティクス / 化学合成 / イメージング / DNAメチル化 / 金属錯体 / RNA修飾 / ＤＮＡメチル化 / ＲＮＡ修飾 / 核酸 / 有機化学 / 癌 / ゲノム / バイオテクノロジー

Outline of Final Research Achievements

Based on the chemical reactions developed by us, the studies on highly efficient detection methods for epigenetic modifications have been carried out. The results are as follows: (i) Highly bright detection of methylation in DNA repeat sequences to understand heterogeneity in tumors, (ii) High performance analysis of the products in demethylation process to make prognostication for tumors efficient, (iii) Chemical reproduction and analysis of histone structures for control of gene expression.

Research Products

• [Journal Article] Efficient peptide ligation between allyl-protected Asp and Cys followed by palladium-mediated deprotection (2018)
  • Author(s): Kamo Naoki、Hayashi Gosuke、Okamoto Akimitsu
  • Journal Title: Chemical Communications Volume: 54 Issue: 34 Pages: 4337-4340
  • DOI: 10.1039/c8cc01965g
  • Peer Reviewed
• [Journal Article] Hybridization-sensitive Fluorescent Oligonucleotide Probe Conjugated with Cell-penetrating Peptides for Enhanced Cellular Uptake (2017)
  • Author(s): Hayashi Gosuke、Tamai Makoto、Okamoto Akimitsu
  • Journal Title: Chemistry Letters Volume: 46 Issue: 12 Pages: 1803-1806
  • DOI: 10.1246/cl.170813
  • NAID: 130006243207
  • Peer Reviewed
• [Journal Article] Regulation of the Stability of the Histone H2A?H2B Dimer by H2A Tyr57 Phosphorylation (2017)
  • Author(s): Sueoka Takuma、Hayashi Gosuke、Okamoto Akimitsu
  • Journal Title: Biochemistry Volume: 56 Issue: 36 Pages: 4767-4772
  • DOI: 10.1021/acs.biochem.7b00504
  • Peer Reviewed
• [Journal Article] Chemical synthesis of dual labeled proteins via differently protected alkynes enables intramolecular FRET analysis (2017)
  • Author(s): Hayashi Gosuke、Kamo Naoki、Okamoto Akimitsu
  • Journal Title: Chemical Communications Volume: 53 Issue: 43 Pages: 5918-5921
  • DOI: 10.1039/c7cc02612a
  • Peer Reviewed
• [Journal Article] DNA-friendly Cu(ii)/TEMPO-catalyzed 5-hydroxymethylcytosine-specific oxidation (2017)
  • Author(s): Matsushita T, Moriyama Y, Nagae G, Aburatani H, Okamoto A
  • Journal Title: Chemical Communications Volume: 53 Issue: 42 Pages: 5756-5759
  • DOI: 10.1039/c7cc02814h
  • Peer Reviewed
• [Journal Article] Chemically-activatable alkyne-tagged probe for imaging microdomains in lipid bilayer membranes (2017)
  • Author(s): Yamaguchi, S.; Matsushita, T.; Izuta, S.; Katada, S.; Ura, M.; Ikeda, T. ;Hayashi, G.; Suzuki, Y.; Kobayashi, Y.; Tokunaga, K.; Ozeki, Y.; Okamoto, A.
  • Journal Title: Sci. Rep. Volume: 7 Issue: 1 Pages: 41007-41007
  • DOI: 10.1038/srep41007
  • Peer Reviewed / Open Access
• [Journal Article] Base-Resolution Analysis of 5-Hydroxymethylcytosine by One-Pot Bisulfite-Free Chemical Conversion with Peroxotungstate. (2016)
  • Author(s): Hayashi G, Koyama K, Shiota H, Kamio A, Umeda T, Nagae G, Aburatani H, Okamoto A.
  • Journal Title: J Am Chem Soc. Volume: 138 Issue: 43 Pages: 14178-14181
  • DOI: 10.1021/jacs.6b06428
  • Peer Reviewed
• [Journal Article] Chemically Activatable Alkyne Tag for Low pH-Enhanced Molecular Labeling on Living Cells (2016)
  • Author(s): Yamaguchi,S.; Ura, M.; Izuta, S.; Okamoto, A.
  • Journal Title: Bioconjugate Chem. Volume: 27 Issue: 9 Pages: 1976-1980
  • DOI: 10.1021/acs.bioconjchem.6b00399
  • Peer Reviewed
• [Journal Article] Rapid nuclear import of short nucleic acids (2016)
  • Author(s): Kitagawa, M.; Okamoto, A.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 26 Issue: 19 Pages: 4568-4570
  • DOI: 10.1016/j.bmcl.2016.08.085
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] In vitro and in cell analysis of chemically synthesized histone H2A with multiple modifications (2016)
  • Author(s): Gosuke Hayashi, Takuma Sueoka, Akimitsu Okamoto
  • Journal Title: Chemical Communications Volume: 52 Issue: 28 Pages: 4999-5002
  • DOI: 10.1039/c5cc10555b
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Diazirine Photocrosslinking Recruits Activated FTO Demethylase Complexes for Specific N6-methyladenosine Recognition (2015)
  • Author(s): Jeong, H. S.; Hayashi, G.; Okamoto, A
  • Journal Title: ACS Chem. Biol. Volume: 10 Issue: 6 Pages: 1450-1455
  • DOI: 10.1021/cb5010096
  • Peer Reviewed
• [Presentation] Chemical approach to nucleic acid diversity (2017)
  • Author(s): Akimitsu Okamoto
  • Organizer: JSPS-NRCT 2017 and IAMPS 33
  • Place of Presentation: タイ・バンコク
  • Year and Date: 2017-03-02
  • Int'l Joint Research / Invited
• [Presentation] Evaluation of Histone H2A-H2B Dimer based on Protein Chemical Synthesis (2017)
  • Author(s): Takuma Sueoka, Gosuke Hayashi, Daisuke Sakakibara and Akimitsu Okamoto
  • Organizer: 25th American Peptide Symposium
  • Int'l Joint Research
• [Presentation] Silyl-protected Alkynes for Multiple Labeling of Chemically Synthesized Protein (2017)
  • Author(s): G. Hayashi, N. Kamo and A. Okamoto
  • Organizer: 25th American Peptide Symposium
  • Int'l Joint Research
• [Presentation] ヌクレオソーム動態解析を指向した化学合成ヒストンタンパク質 (2017)
  • Author(s): 林 剛介、末岡 拓馬、岡本 晃充
  • Organizer: 第55回日本生物物理学会年会
• [Presentation] アリル保護基を用いたAsp-Cys間のNCL連結法の開発 (2017)
  • Author(s): 加茂 直己、林 剛介、岡本 晃充
  • Organizer: 第11回バイオ関連化学シンポジウム
• [Presentation] 化学合成ヒストンを用いたエピジェネティクス解析プラットフォームの構築 (2017)
  • Author(s): 林 剛介、末岡 拓馬、坂元 亮介、榊原 大輔、石橋 真帆、岡本 晃充
  • Organizer: 日本ケミカルバイオロジー学会 第12回年会
• [Presentation] タンパク質化学合成を利用したヒストンH2A-H2B研究への展開 (2017)
  • Author(s): 末岡 拓馬、林 剛介、榊原 大輔、岡本 晃充
  • Organizer: 日本ケミカルバイオロジー学会 第12回年会
• [Presentation] 5-Hydroxymethylcytosine-Specific Oxidation: DNA -Friendly Cu(II)/TEMPO-Catalyzed Oxidation and Apprications (2016)
  • Author(s): Akimitsu Okamoto
  • Organizer: The 22th International Round Table on Nucleosides, Nucleotides and Nucleic Acids (XXII IRT)
  • Place of Presentation: フランス・パリ
  • Year and Date: 2016-07-18
  • Int'l Joint Research