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Synthetic strategy for chemical methylome analyses

Research Project

Project/Area Number 17H02213
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical biology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

SOHTOME Yoshihiro  国立研究開発法人理化学研究所, 開拓研究本部, 専任研究員 (50431888)

Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2021: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2020: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsタンパク質メチル化 / 補酵素 / 酵素 / 阻害剤 / 有機合成化学 / プロテオーム / 検出プローブ / 非ヒストン / メチローム解析 / 触媒反応 / エピゲノム
Outline of Final Research Achievements

Protein methylation, catalyzed by protein methyltransferases (MTases) using S-adenosyl-L-methionine (SAM ) as a methyl donor, is an important post-translational modification. We have focused on the development of a new chemical methylome strategy, using propargylic Se-adenosyl-L-selenomethionine (ProSeAM), an analog of SAM, enabling to identify substrates and methylation sites. Integrating ProSeAM with SILAC (stable isotope labeling by amino acids in cell culture) led us to the development of PMS (ProSeAM/MTase/SILAC) and PIS (ProSeAM/Inhibitor/SILAC), which are useful tools for protein substrate discovery and inhibitor profiling.

Academic Significance and Societal Importance of the Research Achievements

タンパク質メチル化反応は、環境に応答して可逆的に変動する翻訳後修飾反応の1つである。しかしながら、メチル化されたタンパク質を効率的に濃縮する方法が限られているため、酵素と基質タンパク質とを紐付けるメチローム解析は遅れている。本研究では、タンパク質メチル化反応をモデル題材としてとらえ、有機合成化学主導で、他の分野の研究者、特に生物学者が『興味をもつ・分かる』、そして『使える』分子技術の創出を目指した。本研究を通じて、これまで見逃されてきた数種のタンパク質メチル化反応を見出すことに成功し、それらの制御を目指した新しいタイプの阻害剤を創出することにも成功した。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (46 results)

All 2022 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 5 results) Presentation (25 results) (of which Int'l Joint Research: 2 results,  Invited: 14 results) Book (2 results) Remarks (8 results)

  • [Int'l Joint Research] University of North Carolina(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Propargylic Se-adenosyl-l-selenomethionine: A Chemical Tool for Methylome Analysis2021

    • Author(s)
      Sohtome Yoshihiro、Shimazu Tadahiro、Shinkai Yoichi、Sodeoka Mikiko
    • Journal Title

      Accounts of Chemical Research

      Volume: 54 Issue: 20 Pages: 3818-3827

    • DOI

      10.1021/acs.accounts.1c00395

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamics in Catalytic Asymmetric Diastereoconvergent (3 + 2) Cycloadditions with Isomerizable Nitrones and α-Keto Ester Enolates2021

    • Author(s)
      Ezawa Tetsuya、Sohtome Yoshihiro、Hashizume Daisuke、Adachi Masaya、Akakabe Mai、Koshino Hiroyuki、Sodeoka Mikiko
    • Journal Title

      Journal of the American Chemical Society

      Volume: 143 Issue: 24 Pages: 9094-9104

    • DOI

      10.1021/jacs.1c02833

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes2021

    • Author(s)
      Erna Davydova, Tadahiro Shimazu et al,
    • Journal Title

      Nat. Commun.

      Volume: 12 Issue: 1 Pages: 891-891

    • DOI

      10.1038/s41467-020-20670-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cross-Coupling Reactions of Persistent Tertiary Carbon Radicals,2021

    • Author(s)
      Yoshihiro Sohtome, Kyohei Kanomata, Mikiko Sodeoka
    • Journal Title

      Bull. Chem. Soc. Jpn.

      Volume: 94 Issue: 3 Pages: 1066-1079

    • DOI

      10.1246/bcsj.20200376

    • NAID

      130008021808

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regiodivergent Oxidative Cross-Coupling of Catechols with Persistent tert-Carbon Radicals2020

    • Author(s)
      Masumi Sugawara, Rikako Ohnishi, Tetsuya Ezawa, Mai Akakabe, Miki Sawamura, Daiki Hojo, Daisuke Hashizume, Yoshihiro Sohtome, Mikiko Sodeoka
    • Journal Title

      ACS Catalysis

      Volume: 10 Issue: 21 Pages: 895-898

    • DOI

      10.1021/acscatal.0c03986

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Unveiling epidithiodiketopiperazine as a non-histone arginine methyltransferase inhibitor by chemical protein methylome analyses2018

    • Author(s)
      Yoshihiro Sohtome, Tadahiro Shimazu, Joaquin Barjau, Shinya Fujishiro, Mai Akakabe, Naoki Terayama, Kosuke Dodo, Akihiro Ito, Minoru Yoshida, Yoichi Shinkai, Mikiko Sodeoka
    • Journal Title

      Chem. Commun.

      Volume: 54 Issue: 66 Pages: 9202-9205

    • DOI

      10.1039/c8cc03907k

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tri-methylation of ATF7IP by G9a/GLP recruits the chromodomain protein MPP8.2018

    • Author(s)
      Tsusaka T, Kikuchi M, Shimazu T, Suzuki T, Sohtome Y, Akakabe M, Sodeoka M, Dohmae N, Takashi Umehara T, Shinkai Y*.
    • Journal Title

      Epigenetics and chromatin.

      Volume: 11 Issue: 1 Pages: 56-56

    • DOI

      10.1186/s13072-018-0231-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of Chaetocin and S-Adenosylmethionine Analogues as Tools for Studying Protein Methylation2018

    • Author(s)
      Yoshihiro Sohtome, Mikiko Sodeoka
    • Journal Title

      Chem. Rec.

      Volume: 18 Issue: 12 Pages: 1660-1671

    • DOI

      10.1002/tcr.201800118

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Naked d-orbital in a centrochiral Ni(II) complex as a catalyst for asymmetric [3+2] cycloaddition2017

    • Author(s)
      Sohtome Yoshihiro、Nakamura Genta、Muranaka Atsuya、Hashizume Daisuke、Lectard Sylvain、Tsuchimoto Teruhisa、Uchiyama Masanobu、Sodeoka Mikiko
    • Journal Title

      Nature Commun.

      Volume: 8 Issue: 1 Pages: 14875-14875

    • DOI

      10.1038/ncomms14875

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Catalytic Enantioselective [3+2] Cycloaddition of a‐Keto Ester Enolates and Nitrile Oxides2017

    • Author(s)
      Samuel L. Bartlett, Yoshihiro Sohtome, Daisuke Hashizume, Peter S. White, Miki Sawamura, Jeffrey S. Johnson, Mikiko Sodeoka
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 139 Issue: 25 Pages: 8661-8666

    • DOI

      10.1021/jacs.7b03782

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Dynamic catalytic diastereoconvergent (3+2) cycloaddition with alpha-keto ester enolates2022

    • Author(s)
      Yoshihiro Sohtome, Tetsuya Ezawa, Daisuke Hashizume, Masaya Adachi, Mai Akakabe, Hiroyuki Koshino, Mikiko Sodeoka
    • Organizer
      日本化学会第102春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 鍵と鍵穴からinduced-fitへ: ジアステレオ収束的(3+2)環化付加2021

    • Author(s)
      五月女宜裕
    • Organizer
      新領域研究グループ「分子空間化学」シンポジウム2020
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 合成化学を起点としたケミカルメチローム解析2021

    • Author(s)
      五月女宜裕
    • Organizer
      日本薬学会第141回年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 動的反応化学: 分子触媒と酵素の理解と制御を目指して2021

    • Author(s)
      五月女宜裕
    • Organizer
      京都大学化学研究所講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 吸熱的結合形成反応: 酸化的分子変換の高度化を目指して2020

    • Author(s)
      五月女宜裕
    • Organizer
      日本化学会新領域研究グループ「分子空間化学」2020オンラインシンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] タンパク質メチル化反応の検出と制御を目指して2020

    • Author(s)
      五月女宜裕
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 分野の垣根を超えた有機反応化学を目指して2019

    • Author(s)
      五月女宜裕
    • Organizer
      北里大学大学院感染制御科学府、公開セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 分子触媒と酵素の理解と制御を目指して2019

    • Author(s)
      五月女宜裕
    • Organizer
      柴﨑セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 安定炭素ラジカル種を用いた連続四置換炭素の構築法の開発2019

    • Author(s)
      大西理華子、菅原真純、赤壁麻衣、五月女宜裕、越野広雪、袖岡幹子
    • Organizer
      日本化学会第99回春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] a-ケトエステルエノレートとC-シアノニトロンとの触媒的不斉[3+2]環化付加型反応2019

    • Author(s)
      江澤哲也、足立雅弥、赤壁麻依、五月女宜裕、袖岡幹子
    • Organizer
      日本化学会第99回春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Strategies to control chiral environments constructed by molecular catalysts and enzymes2019

    • Author(s)
      Yoshihiro Sohtome
    • Organizer
      日本化学会第99回春季年会 (2019) 特別企画講演
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 安定炭素ラジカル種を用いる連続四置換炭素の構築及びスペクトル解析2018

    • Author(s)
      大西理華子、菅原真純、赤壁麻衣、五月女宜裕、越野広雪、袖岡幹子
    • Organizer
      第8回CSJ化学フェスタ2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] 金属中心キラリティー内包型遷移金属錯体を用いる触媒的不斉反応2018

    • Author(s)
      五月女宜裕
    • Organizer
      錯体化学若手の会・関東支部前期勉強会2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 酸素を用いる酸化的炭素-炭素結合形成反応2018

    • Author(s)
      五月女宜裕
    • Organizer
      新領域研究グループ「分子空間化学」シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Centrochiral transition metal complexes for catalytic asymmetric [3+2] cycloaddition of alpha-ketoester enolates2018

    • Author(s)
      Yoshihiro Sohtome, Mikiko Sodeoka
    • Organizer
      International Congress on Pure & Applied Chemistry (ICPAC) 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Controlling regioselectivity in the aerobic oxidative hetero-coupling of catechols2018

    • Author(s)
      Masumi Sugawara, Daiki Hojo, Miki Sawamura, Daisuke, Hashizume, Yoshihiro Sohtome, Mikiko Sodeoka
    • Organizer
      日本化学会第98回春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Catalytic Asymmetric [3+2] Cycloaddition of a-Ketoester Enolates and Nitrile Oxides2018

    • Author(s)
      Samuel L. Bartlett, Yoshihiro Sohtome, Daisuke Hashizume, Peter S. White, Miki Sawamura, Jeffrey S. Johnson, Mikiko Sodeoka
    • Organizer
      日本化学会第98回春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 安定な炭素ラジカル種を用いたヘテロカップリング反応の基質展開2018

    • Author(s)
      大西理華子、菅原真純、五月女宜裕、袖岡 幹子
    • Organizer
      日本化学会第98回春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ProSeAMを用いるケミカルメチローム解析及びタンパク質メチル化阻害剤探索2017

    • Author(s)
      五月女宜裕、島津忠広、Barjau Joaquin、藤城信哉、赤壁麻依、寺山直樹、どど孝介、伊藤昭博、吉田稔、眞貝洋一、袖岡幹子
    • Organizer
      日本ケミカルバイオロジー学会 第12回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ラジカル-ラジカルヘテロカップリング反応を基軸とする連続四級炭素の構築: N-Bocオキシインドール二量体の構造解析2017

    • Author(s)
      菅原真純、五月女宜裕、橋爪大輔、 北條大樹、澤村 美紀、村中厚哉、内山真伸、袖岡 幹子
    • Organizer
      第6回JACI/GSCシンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Centrochiral Ni(II) complex that enables the merger of enolate formation and H-bonding activation2017

    • Author(s)
      Yoshihiro Sohtome, Genta Nakamura, Atsuya Muranaka, Daisuke Hashizume, Sylvain Lectard, Teruchira Tsuchimoto, Masanobu Uchiyama, Mikiko Sodeoka
    • Organizer
      29th International Symposium on Chirality (Chirality 2017; ISCD-29)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 歪みを内包するNi(II)錯体の創製と触媒的不斉[3+2]環化付加型反応への展開2017

    • Author(s)
      五月女宜裕、中村元太、村中厚哉、橋爪大輔、レクターシルバン、土本晃久、内山真伸、袖岡幹子
    • Organizer
      第64回有機金属化学討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ケミカルエピゲノムの新展開2017

    • Author(s)
      五月女宜裕
    • Organizer
      新領域研究グループ『精密物質変換のための分子空間化学』 2017山形シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 特異な不斉空間制御を可能とする有機触媒・遷移金属錯体触媒2017

    • Author(s)
      五月女宜裕
    • Organizer
      新化学技術推進協会、先端化学・材料技術部会、高選択性反応分科会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 分野、研究室の垣根を超えた異分野融合型-有機合成化学2017

    • Author(s)
      五月女宜裕
    • Organizer
      中堅・若手リーダーのためのYUGOKAFE NExT
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Book] "Design of the chiral environment for catalytic asymmetric acid-base catalysis" in Designed Molecular Space in Material Science and Catalysis2018

    • Author(s)
      Yoshihiro Sohtome, Kazuo Nagasawa, Mikiko Sodeoka
    • Total Pages
      262
    • Publisher
      Springer
    • ISBN
      9789811312564
    • Related Report
      2018 Annual Research Report
  • [Book] 実験医学別冊 エピジェネティクス実験スタンダード: もう悩まない!ゲノム機能制御の読み解き方/メ チル化酵素の新規標的分子の網羅的解析2017

    • Author(s)
      島津忠広、五月女宜裕、袖岡幹子、眞貝洋一
    • Total Pages
      398
    • Publisher
      羊土社
    • ISBN
      475810199X
    • Related Report
      2017 Annual Research Report
  • [Remarks] ジアステレオ収束的な(3+2)環化付加型反応の開発-鍵と鍵穴から誘導適合へ-

    • URL

      https://www.riken.jp/press/2021/20210610_3/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 動的ジアステレオ収束型触媒反応

    • URL

      https://www.chemistry.or.jp/division-topics/2021/10/post-202.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 位置多様性・脱水素型クロスカップリング

    • URL

      https://www.chem-station.com/blog/2020/11/coupling.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 位置多様性・脱水素型クロスカップリングの開発

    • URL

      https://www.riken.jp/pr/news/2020/20201218_2/index.html?fbclid=IwAR20Ccl_UckP5cODEkA6cLTak6jTkz7lo

    • Related Report
      2020 Annual Research Report
  • [Remarks] 位置多様性・脱水素型クロスカップリング -ラジカル・酸/塩基反応の協奏により反応位置を操る-

    • URL

      https://www.riken.jp/press/2020/20201022_1/index.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 理化学研究所プレスリリース

    • URL

      http://www.riken.jp/pr/press/2018/20180806_2/

    • Related Report
      2018 Annual Research Report
  • [Remarks] Chem-Station スポットライトリサーチ

    • URL

      https://www.chem-station.com/blog/2018/09/methylation.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] Cover picture in Chem. Rec.

    • URL

      https://onlinelibrary.wiley.com/doi/10.1002/tcr.201881201

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2023-01-30  

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