Chenical biology research using diketopiperazine-based anti-microtubule agent.

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790118
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Drug development chemistry
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: YAMAZAKI Yuri Tokyo University of Pharmacy and Life Science, 薬学部, 助手 (70459725)
• Project Period (FY): 2009 – 2010
• Keywords: 分子認識 / 医薬品化学 / 癌 / 生体分子 / 薬学

Research Abstract

In order to understand the precise binding site of diketopiperadine-based anti-microtubule agent 'plinabulin' on tubulin, we designed and synthesized biotin-tagged plinabulin derivatives as chemical probes. Since these derivatives all showed a significant binding ability to tubulin and cytotoxicity, we performed tubulin photoaffinity labeling study. These results suggested that plinabulin derivatives may bind at the boundary region formed between the α-and β-tubulin subunits around the colchicine binding site, but not inside the site, to effectively disrupt the interaction between the two tubulin subunits, thereby producing microtubule depolymerization.

Research Products

• [Journal Article] Tubulin photoaffinity labeling study with a plinabulin chemical probe possessing a biotin tag at the oxazole. (2011)
  • Author(s): Yuri Yamazaki, Yui Kido, Koushi Hidaka, Hiroyuki Yasui, Yoshiaki Kiso, Fumika Yakushiji, Yoshio Hayashi
  • Journal Title: Bioorganic & Medicinal Chemistry 19 Pages: 595-602
  • Peer Reviewed
• [Journal Article] Anti-microtubule 'plinabulin' chemical probe KPU-244-B3 labeled both α- and β-tubulin (2010)
  • Author(s): Yuri Yamazaki, Makiko Sumikura, Koushi Hidaka, Hiroyuki Yasui, Yoshiaki Kiso, Fumika Yakushiji, Yoshio Hayashi
  • Journal Title: Bioorganic & Medicinal Chemistry 18 Pages: 3169-3174
  • Peer Reviewed
• [Journal Article] Total synthesis of (+)-neganycin and its 5-epi-derivatives. (2010)
  • Author(s): Shigenobu Nishiguchi, Magne O.Sydnes, Akihiro Taguchi, Thomas Regnier, Tetsuya Kajimoto, Manabu Node, Yuri Yamazaki, Fumika Yakushiji, Yoshiaki Kiso, Yoshio Hayashi
  • Journal Title: Tetrahedron 66 Pages: 314-320
  • Peer Reviewed
• [Journal Article] Synthesis and antimicrobial activity of (+)-negamycin derivatives focused on the hydrazine amide moiety. (2010)
  • Author(s): Akihiro Taguchi, Mayuko Ina, Yuri Yamazaki, Fumika Yakushiji, Yoshikazu Takahashi, Yoshiaki Kiso, Yoshio Hayashi
  • Journal Title: Peptide Science 46 Pages: 317-318
  • Peer Reviewed
• [Journal Article] Synthesis and structure-activity relationship study of cyclic dipeptide-based microtubule depolymerization agents with a benzophenone structure. (2010)
  • Author(s): Makiko Sumikura, Yuri Yamazaki, Tomoko Yoshida, Yuki Mori, Hiroyuki Yasui, Yoshiaki Kiso, Saskia Neuteboom, Barbara Potts, G.Kenneth Lloyd, Yoshio Hayashi
  • Journal Title: Peptide Science 46 Pages: 315-316
  • Peer Reviewed
• [Journal Article] Acid catalyzed monodehydro-2,5-diketopiperazine formation from N-α-ketoacyl amino acid amides. (2009)
  • Author(s): Yuri Yamazaki, Yuki Mori, Akiko Oda, Yuka Okuno, Yoshiaki Kiso, Yoshio Hayashi
  • Journal Title: Tetrahedron 65 Pages: 3688-3694
  • Peer Reviewed
• [Journal Article] Acid catalyzed monodehydro-2,5-diketopiperazine formation toward natural productsynthesis. (2009)
  • Author(s): Yuri Yamazaki, Yuki Mori, Akiko Oda, Yoshiaki Kiso, Yoshio Hayashi
  • Journal Title: Peptides Breaking Away Proc.21st Amer.Peptide Symp.(Ed.Michal Lebl) Pages: 54-55
  • Peer Reviewed
• [Presentation] 酸触媒環化反応を用いたモノデヒドロ-2,5-ジケトピペラジン化合物の合成研究 (2010)
  • Author(s): 山崎有理、森雄樹、小田暁子、奥野友香、木曽良明、林良雄
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 20100328-20100330
• [Presentation] Plinabulin' a diketopiperazine-type vascular targeting anti-cancer agent based on microtubule depolymerization activity. (2010)
  • Author(s): Yoshio Hayashi, Yuri Yamazaki, Makiko Sumikura, Tomoko Yoshida, Yuki Mori, Hiroyuki Yasui, Kyoko Kohno, Yoshiaki Kiso, Saskia Neuteboom, Barbara Potts, G.Kenneth Lloyd
  • Organizer: ACS Spring 2010 National Meeting & Exposition
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20100321-20100325
• [Presentation] Development of chemical probes towards the elucidation of binding mechanism of plinabulin, a cyclicdipeptide based anti-microtubule agent. (2010)
  • Author(s): Yuri Yamazaki, Yui Kido, Koushi Hidaka, Hiroyuki Yasui, Yoshiaki Kiso, Fumika Yakushiji, Yoshio Hayashi
  • Organizer: 5th International Peptide Symposium in conjunction with 47th Japanese Peptide Symposium
  • Place of Presentation: Kyoto
  • Year and Date: 2010-12-04
• [Presentation] 新生血管を障害するチューブリン重合阻害剤の創製 (2010)
  • Author(s): 林良雄
  • Organizer: 日本放射線腫瘍学会第23回学術大会
  • Place of Presentation: 千葉
  • Year and Date: 2010-11-18
• [Presentation] 微小管作用薬Plinabulinの作用様式解明を目指したケミカルプローブの開発 (2010)
  • Author(s): 山崎有理、城戸結衣、日高興士、安井裕之、木曽良明、薬師寺文華、林良雄
  • Organizer: 第29回メディシナルケミストリーシンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2010-11-17
• [Presentation] Plinabulinケミカルプローブの開発とプローブの機能評価 (2010)
  • Author(s): 山崎有理、林良雄
  • Organizer: 第14回日本がん分子標的治療学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-06
• [Presentation] 新生血管内皮細胞を障害するジケトピペラジン型微小管脱重合剤の創製 (2010)
  • Author(s): 林良雄、山崎有理
  • Organizer: 第14回日本がん分子標的治療学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-06
• [Presentation] ジケトピペラジン型微小管作用薬Plinabulinを基盤としたケミカルプローブの開発 (2010)
  • Author(s): 山崎有理、角倉真紀子、河野享子、日高興士、安井裕之、木曽良明、薬師寺文華、林良雄
  • Organizer: 日本ケミカルバイオロジー学会第5回年会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-18
• [Presentation] ベンゾフェノン構造を有するジケトピペラジン型微小管脱重合剤の開発 (2009)
  • Author(s): 角倉真紀子、山崎有理、吉田智子、森雄樹、安井裕之、木曽良明、Saskia Neuteboom, Barbara Potts, G.Kenneth Lloyd, 林良雄
  • Organizer: 第28回メディシナルケミストリーシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20091125-20091127
• [Presentation] Plinabulin" a cyclic dipeptide-based vascular targeting anti-cancer agent based on microtubule depolymerization activity. (2009)
  • Author(s): Yoshio Hayashi, Yuri Yamazaki, Makiko Sumikura, Tomoko Yoshida, Yuki Mori, Hiroyuki Yasui, Kyoko Kohno, Yoshiaki Kiso, Saskia Neuteboom, Barbara Potts, G.Kenneth Lloyd
  • Organizer: 3rd Asia-Pacific International Peptide Symposium/13th Korean Peptide and Protein Symposium
  • Place of Presentation: Jeju Island, Korea
  • Year and Date: 20091108-20091111
• [Presentation] Synthesis and structure-activity relationship study of cyclic dipeptide-based microtubule depolymerization agents with a benzophenone structure. (2009)
  • Author(s): Makiko Sumikura, Yuri Yamazaki, Tomoko Yoshida, Yuki Mori, Hiroyuki Yasui, Yoshiaki Kiso, Saskia Neuteboom, Barbara Potts, G.Kenneth Lloyd, Yoshio Hayashi
  • Organizer: 46th Japanese Peptide Symposium
  • Place of Presentation: Kitakyusyu
  • Year and Date: 20091104-20091106
• [Presentation] Cyclic dipeptide-based microtubule depolymerization agents as vascular targeting anti-cancer drugs (2009)
  • Author(s): Yuri Yamazaki, Makiko Sumikura, Tomoko Yoshida, Yuki Mori, Hiroyuki Yasui, Kyoko Kohno, Yoshiaki Kiso, Gordafaried Deyanat-Yazdi, Saskia Neuteboom, Barbara Potts, G.Kenneth Lloyd, Yoshio Hayashi
  • Place of Presentation: Chains, Australia
  • Year and Date: 20090823-20090827
• [Presentation] Acid catalyzed monodehydro-2,5-diketopiperazine formation toward natural product synthesis. (2009)
  • Author(s): Yuri Yamazaki, Yuki Mori, Akiko Oda, Yoshiaki Kiso, Yoshio Hayashi
  • Organizer: 21st American Peptide Symposium : Breaking Away
  • Place of Presentation: Bloomington, USA
  • Year and Date: 20090607-20090612
• [Remarks] ホームページ等
• [Remarks] 東京薬科大学ホームページ、研究室紹介
  • URL: http://www.toyaku.ac.jp/departments/pharmacy04_03_05_j.html