Fluorescence screening and imaging by chemical probes for detecting histone deacetylases/demethylases activity

• Project/Area Number: 16K13099
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: Osaka University
• Principal Investigator: KIKUCHI Kazuya 大阪大学, 工学研究科, 教授 (70292951)
• Project Period (FY): 2016-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 蛍光プローブ / ヒストン脱メチル化酵素 / エピジェネティクス / ヒストン脱アセチル化酵素 / リジン脱メチル化酵素 / エピゲノム

Outline of Final Research Achievements

Fluorescent probes were developed for detection of lysine demethylase (KDM) activity. This fluorescent probe produced a fluorescent coumarin upon lysine demethylation by utilizing the intramolecular transesterification mechanism. As results, KDM activity was successfully detected with a single-step manipulation for the first time. The probe will be useful for understanding the role of KDM and contribute to development of drugs targeting KDM activity.

Research Products

• [Journal Article] Photostable and Photoswitching Fluorescent Dyes for Super-resolution Imaging (2017)
  • Author(s): M. Minoshima, K. Kikuchi
  • Journal Title: Journal of Biological Inorganic Chemistry Volume: - Issue: 5 Pages: 1-14
  • DOI: 10.1007/s00775-016-1435-y
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Enzyme-Triggered Compound Release using Functionalized Antimicrobial Peptide Derivatives (2017)
  • Author(s): Shin Mizukami, Masayoshi Kashibe, Kengo Matsumoto, Yuichiro Hori, Kazuya Kikuchi
  • Journal Title: Chem. Sci. Volume: 8 Issue: 4 Pages: 3047-3053
  • DOI: 10.1039/c6sc04435b
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Fluorogenic Probes Reveal a Role of GLUT4 N-glycosylation in Intracellular Trafficking (2016)
  • Author(s): S. Hirayama, Y. Hori, Z. Benedek, T. Suzuki, K. Kikuchi
  • Journal Title: Nature Chemical Biology Volume: 12 Issue: 10 Pages: 853-859
  • DOI: 10.1038/nchembio.2156
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Real-Time Intravital Imaging of pH Variation Associated with Osteoclast Activity (2016)
  • Author(s): Hiroki Maeda, Toshiyuki Kowada, Junichi Kikuta, Masayuki Furuya, Mai Shirazaki, Shin Mizukami, Masaru Ishii, Kazuya Kikuchi
  • Journal Title: Nat. Chem. Biol. Volume: 12 Issue: 8 Pages: 579-585
  • DOI: 10.1038/nchembio.2096
  • Peer Reviewed
• [Journal Article] Fabrication of ‘Clickable’ Polyfluorene Nanowires with High Aspect Ratio as Biological Sensing Platforms (2016)
  • Author(s): T. Wasin, K. Enomoto, T. Sakurai, V. Padalkar, H. Cheng, M. Tang, A. Horio, D., Sakamaki, M. Omichi, A. Saeki, K. Kikuchi, Y. Hori, A. Chiba, Y. Saito, T. Kamiya, M. Sugimoto, S. Seki
  • Journal Title: ACS Sensors Volume: 6 Issue: 6 Pages: 766-774
  • DOI: 10.1021/acssensors.6b00070
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Real-time Intravital Imaging of pH Variation Associated with Osteoclast Activity Using BODIPY Based Two Photon Excitation Probes (2016)
  • Author(s): K. Kikuchi
  • Organizer: The 8th Asian Biological Inorganic Chemistry Conference (AsBIC VIII)
  • Place of Presentation: Auckland, New Zealand
  • Year and Date: 2016-12-05
  • Int'l Joint Research / Invited
• [Presentation] Real-time Intravital Imaging of pH Variation Associated with Osteoclast Activity (2016)
  • Author(s): K. Kikuchi
  • Organizer: MSMLG 2016, 5th International Conference on Molecular Sensors and Molecular Logic Gates
  • Place of Presentation: Bath, UK
  • Year and Date: 2016-07-24
  • Int'l Joint Research / Invited
• [Presentation] Real-time Intravital Imaging of pH Variation Associated with Osteoclast Activity Using BODIPY Based Two Photon Excitation Probes (2016)
  • Author(s): K. Kikuchi
  • Organizer: ICPP-9, 9th International Conference on Porphyrins and Phthalocyanines
  • Place of Presentation: Nanjing, China
  • Year and Date: 2016-07-03
  • Int'l Joint Research / Invited