Preparation of histone demethylase inhibitors based on substrate specificity

• Project/Area Number: 26460159
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Waseda University
• Principal Investigator: Kakizawa Taeko 早稲田大学, 理工学術院, 講師(任期付) (60445963)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 酵素阻害剤 / 創薬化学 / ペプチド / 創薬科学

Outline of Final Research Achievements

Lysine-specific demethylase 1 (LSD1) is a flavin-dependent enzyme that removes methyl groups from lysine residues at the fourth position of histone H3. Several substrate-based LSD1 inhibitors that have LSD1 inactivator motifs on the side chain of the lysine residue in histone H3 peptide were prepared. Inhibitory activity of the synthesized compounds was evaluated using recombinant LSD1.

Research Products

• [Journal Article] Histone H3 peptides incorporating modified lysine residues as lysine-specific demethylase 1 inhibitors (2018)
  • Author(s): Taeko Kakizawa, Yosuke Ota, Yukihiro Itoh, Takayoshi Suzuki
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 28 Issue: 2 Pages: 167-169
  • DOI: 10.1016/j.bmcl.2017.11.035
  • Peer Reviewed
• [Journal Article] Evaluation of phenylcyclopropylamine compounds by enzymatic assay of lysine-specific demethylase 2 in the presence of NPAC peptide (2016)
  • Author(s): Taeko Kakizawa, Tamio Mizukami, Yukihiro Itoh, Makoto Hasegawa, Ryuzo Sasaki, Takayoshi Suzuki
  • Journal Title: Bioorganic and Medicinal Chemistry Letters Volume: 26 Issue: 4 Pages: 1193-1195
  • DOI: 10.1016/j.bmcl.2016.01.036
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Histone H3 peptide based LSD1-selective inhibitors (2015)
  • Author(s): Taeko Kakizawa, Yosuke Ota, Yukihiro Itoh, Hiroki Tsumoto, Takayoshi Suzuki
  • Journal Title: Bioorganic and medicinal chemistry letters Volume: 25 Issue: 9 Pages: 1925-1928
  • DOI: 10.1016/j.bmcl.2015.03.030
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Linking of phosphinidene-capped triruthenium carbonyl clusters with diphosphine ligands (2015)
  • Author(s): Taeko Kakizawa , Hisako Hashimoto, Hiromi Tobita
  • Journal Title: INORGANICA CHIMICA ACTA Volume: 425 Pages: 7-10
  • DOI: 10.1016/j.ica.2014.09.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Lysine-Specific Demethylase 1 Inhibitory Activity of Histone H3 Peptides Incorporating Modified Lysine 4 (2017)
  • Author(s): Taeko Kakizawa, Yosuke Ota, Yukihiro Itoh, and Takayoshi Suzuki
  • Organizer: 第 54 回ペプチド討論会
• [Presentation] Modification of the Lysine Residue of Histone H3 Peptides as Lysine-Specific Demethylase 1 inhibitors (2016)
  • Author(s): Taeko Kakizawa, Takayoshi Suzuki
  • Organizer: 第53回ペプチド討論会
  • Place of Presentation: 京都テルサ
  • Year and Date: 2016-10-26
• [Presentation] Evaluation of phenylcyclopropylamine-type inhibitors by an in vitro lysine-specific demethylase 2 assay in the presence of NPAC dodecapeptide (2015)
  • Author(s): Taeko Kakizawa, Tamio Mizukami, Yukihiro Itoh, Takayoshi Suzuki
  • Organizer: 第52回 ペプチド討論会
  • Place of Presentation: 平塚中央公民館
  • Year and Date: 2015-11-16
• [Presentation] Structure-Activity Relationship Studies of the Peptidic Inactivators of Histone Demethylase LSD1 (2014)
  • Author(s): Taeko Kakizawa, Yosuke Ota, Yukihiro Itoh, Takayoshi Suzuki
  • Organizer: 第51回ペプチド討論会
  • Place of Presentation: 徳島大学蔵本キャンパス
  • Year and Date: 2014-10-22 – 2014-10-24
• [Presentation] Truncation Studies of Histone H3 Peptide Analogs as Lysine-Specific Demethylase 1 Inactivators (2014)
  • Author(s): Taeko Kakizawa, Yosuke Ota, Yukihiro Itoh, Takayoshi Suzuki
  • Organizer: 第51回ペプチド討論会
  • Place of Presentation: 徳島大学蔵本キャンパス
  • Year and Date: 2014-10-22 – 2014-10-24