Synthesis and biological activity of cyclic diadenylic acid and its derivatives

• Project/Area Number: 22750148
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Chemistry related to living body
• Research Institution: Nagoya University
• Principal Investigator: TSUKAMOTO Masaki 名古屋大学, 情報科学研究科, 助教 (10362295)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 天然物有機化学 / 環状ジアデニル酸 / ホスホロアミダイト法 / ホスホトリエステル法

Research Abstract

We established a practical synthesis of cyclic bis(3'-5')diadenylic acid (c-di-AMP), which was recently identified as a second messenger monitoring DNA integrity during sporulation in the soil bacterium Bacillus subtilis. Using the synthetic c-di-AMP obtained by ourmethod, we revealed that c-di-AMP promotes the cell division of Chlamydomonas reinhardtii, a kind of freshwater green algae. The three 2'-modified c-di-AMPs synthesized by our method were also found to enhance the cell division.

Research Products

• [Journal Article] Synthesis of 2'-Modified CyclicBis(3'-5')diadenylic Acids (c-di-AMPs) and Their Promotion of Cell Division in a Freshwater Green Alga (2012)
  • Author(s): T. Tezuka, N. Suzuki, K. Ishida, K.-i. Oyama, S. Aoki, and M. Tsukamoto
  • Journal Title: Chem. Lett Volume: 41 Pages: 1723-1725
  • NAID: 10031135807
  • Peer Reviewed
• [Journal Article] Controlling Glycosyl Bond Conformation of Guanine Nucleosides: Stabilization of the anti Conformer in 5'-O-Ethylguanosine (2012)
  • Author(s): H. Asami, S.-h. Urashima, M. Tsukamoto, A. Motoda, Y. Hayakawa, and H. Saigusa
  • Journal Title: J. Phys. Chem. Lett Volume: 3 Pages: 571-575
  • Peer Reviewed
• [Journal Article] Synthesis of 2&prime;-Modified Cyclic Bis(3&prime;&ndash;5&prime;)diadenylic Acids (<i>c</i>-di-AMPs) and Their Promotion of Cell Division in a Freshwater Green Alga (2012)
  • Author(s): T. Tezuka
  • Journal Title: Chemistry Letters Volume: 41 Issue: 12 Pages: 1723-1725
  • DOI: 10.1246/cl.2012.1723
  • NAID: 130004426483
  • ISSN: 0366-7022, 1348-0715
  • Peer Reviewed
• [Journal Article] Controlling glycosyl bond conformation of guanine nucleosides : stabilization of the anti conformer in 5'-O-ethylguanosine (2012)
  • Author(s): H.Asami, S.Urashima, M.Tsukamoto, A.Motoda, Y.Hayakawa, H.Saigusa
  • Journal Title: Journal of Physical Chemistry Letters Volume: 3 Issue: 5 Pages: 571-575
  • DOI: 10.1021/jz300081e
  • Peer Reviewed
• [Journal Article] Practical Synthesis of Cyclic Bis(3'-5')diadenylic Acid (c-di-AMP). (2011)
  • Author(s): N. Suzuki, K.-i. Oyama, and M. Tsukamoto
  • Journal Title: Chem. Lett. Volume: 40 Pages: 1113-1114
  • NAID: 10029683115
  • Peer Reviewed
• [Journal Article] Practical Synthesis of Cyclic Bis(3'-5')diadenylic Acid (c-di-AMP) (2011)
  • Author(s): N.Suzuki, K.-i.Oyama, M.Tsukamoto
  • Journal Title: Chemistry Letters Volume: 40 Issue: 10 Pages: 1113-1114
  • DOI: 10.1246/cl.2011.1113
  • NAID: 130004426072
  • ISSN: 0366-7022, 1348-0715
  • Peer Reviewed
• [Journal Article] H. Asami, M. Tsukamoto, Y. Hayakawa, and H. Saigusa (2010)
  • Author(s): Gas-Phase Isolation of Diethyl Guanosine 5'-Monophosphate and Its Conformational Assignment
  • Journal Title: Chem. Phys. Volume: 12 Pages: 13918-13921
  • Peer Reviewed
• [Journal Article] Gas-phase isolation of diethyl guanosine 5'-monophosphate and its conformational assignment. (2010)
  • Author(s): H.Asami, M.Tsukamoto, Y.Hayakawa, H.Saigusa
  • Journal Title: Physical Chemistry Chemical Physics Volume: 12 Pages: 13918-13921
  • Peer Reviewed
• [Presentation] 2'-位を修飾した環状ジアデニル酸の合成およびそれらの生物活性 (2013)
  • Author(s): 手塚修文、鈴木紀尊、石田啓悟、尾山公一、青木摂之、 塚本眞幸
  • Organizer: 日本化学会第93 春季年会
  • Place of Presentation: 草津
  • Year and Date: 2013-03-22
• [Presentation] 2'-位を修飾した環状ジアデニル酸の合成およびそれらの生物活性 (2013)
  • Author(s): 塚本眞幸
  • Organizer: 日本化学会第93春季年会
  • Place of Presentation: 草津
• [Presentation] Synthesis of Cyclic Bis(3'-5')diadenylic Acid (c-di-AMP) and Its 2'-Modified Analogs (2012)
  • Author(s): N. Suzuki, K.-i. Oyama, and M. Tsukamoto
  • Organizer: Asian Core Program 2012
  • Place of Presentation: Singapore
  • Year and Date: 2012-12-12
• [Presentation] Synthesis of 2'-Modified Cyclic Bis(3'-5')diadenylic Acids (c-di-AMPs) (2012)
  • Author(s): H. Shirouzu, N. Suzuki, K.-i. Oyama, and M. Tsukamoto
  • Organizer: The 39th International Symposium on Nucleic Acids Chemistry
  • Place of Presentation: Nagoya
  • Year and Date: 2012-11-16
• [Presentation] 環状ジアデニル酸の効率的合成法の開発 (2012)
  • Author(s): 鈴木紀尊、尾山公一、塚本眞幸
  • Organizer: 日本化学会第92 春季年会
  • Place of Presentation: 横浜
  • Year and Date: 2012-03-25
• [Presentation] 環状ジアデニル酸の効率的合成法の開発 (2012)
  • Author(s): 鈴木紀尊、尾山公一、塚本眞幸
  • Organizer: 日本化学会第92春季年会(2012)
  • Place of Presentation: 横浜
  • Year and Date: 2012-03-25
• [Presentation] Facile Synthesis of Cyclic Bis(3'-5')diadenylic Acid (c-di-AMP) (2011)
  • Author(s): N. Suzuki, K.-i. Oyama, and M. Tsukamoto
  • Organizer: Nagoya University Global COE International Symposium on Elucidation and Design of Materials and Molecular Functions & Yoshimasa Hirata Memorial Lectures
  • Place of Presentation: Nagoya
  • Year and Date: 2011-11-29
• [Presentation] Facile Synthesis of Cyclic Bis(3'-5')diadenylic Acid (c-di-AMP) (2011)
  • Author(s): N.Suzuki, K.-i.Oyama, M.Tsukamoto
  • Organizer: Nagoya University Global COE International Symposium on Elucidation and Design of Materials and Molecular Functions & Yoshimasa Hirata Memorial Lectures
  • Place of Presentation: 名古屋
  • Year and Date: 2011-11-29
• [Presentation] 核酸塩基関連分子のレーザー脱離パフォーマンスの改善: サンプルとマトリクス粒子のサイズ調整 (2011)
  • Author(s): 塚島史朗、浅見祐也、元田彩香、塚本眞幸、早川芳宏、三枝洋之
  • Organizer: 第5回分子科学討論会 2011
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-21
• [Presentation] 核酸塩基関連分子のレーザー脱離パフォーマンスの改善:サンプルとマトリクス粒子のサイズ調整 (2011)
  • Author(s): 塚島史朗、浅見祐也、元田彩香、塚本眞幸、早川芳宏、三枝洋之
  • Organizer: 第5回分子科学討論会2011
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-21
• [Presentation] Non-destructive vaporization of GMP facilitated by the phosphoesterification: Conformational preference in the gas phase (2010)
  • Author(s): H. Asami, A. Motoda, M. Tsukamoto, Y. Hayakawa, and H. Saigusa
  • Organizer: The 37th International Symposium on Nucleic Acids Chemistry 2010
  • Place of Presentation: Nagoya
  • Year and Date: 2010-11-11
• [Presentation] Non-destructive vaporization of GMP facilitated by the phosphoesterification : Conformational preference in the gas phase (2010)
  • Author(s): H.Asami, A.Motoda, M.Tsukamoto, Y.Hayakawa, H.Saigusa
  • Organizer: The 37th International Symposium on Nucleic Acids Chemistry 2010
  • Place of Presentation: 横浜
  • Year and Date: 2010-11-11
• [Presentation] グアニンヌクレオチドのリン酸基エステル化による非破壊的気化と赤外振動分光 (2010)
  • Author(s): 浅見祐也、元田彩香、塚本眞幸、早川芳宏、三枝洋之
  • Organizer: 第4回分子科学討論会 2010
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-16
• [Presentation] グアニンヌクレオチドのリン酸基エステル化による非破壊的気化と赤外振動分光 (2010)
  • Author(s): 浅見祐也, 元田彩香, 塚本眞幸, 早川芳宏, 三枝洋之
  • Organizer: 第4回分子科学討論会2010
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-16
• [Presentation] Intact laser desorption of guanosine 5'-monophosphate facilitated by the phosphoesterification - Conformational analysis by infrared vibrational spectroscopy (2010)
  • Author(s): H. Asami, A. Motoda, M. Tsukamoto, Y. Hayakawa, and H. Saigusa
  • Organizer: Molecular and Ionic Clusters Conference 2010
  • Place of Presentation: Niigata
  • Year and Date: 2010-09-08
• [Presentation] Intact laser desorption of guanosine 5'-monophosphate facilitated by the phosphoe sterification-Conformational analysis by infrared vibrational spectroscopy (2010)
  • Author(s): H.Asami, A.Motoda, M.Tsukamoto, Y.Hayakawa, H.Saigusa
  • Organizer: Molecular and Ionic Clusters Conference 2010
  • Place of Presentation: 新潟
  • Year and Date: 2010-09-08
• [Patent(Industrial Property Rights)] 核酸固相合成用リンカー及び担体 (2012)
  • Inventor(s): 塚本眞幸、早川芳宏ら
  • Industrial Property Rights Holder: 名古屋大学、日東電工(株)
  • Industrial Property Number: 2012-016895
  • Filing Date: 2012-01-30
• [Patent(Industrial Property Rights)] 核酸固相合成用リンカー及び担体 (2012)
  • Inventor(s): 塚本眞幸, 鈴木紀尊, 早川芳宏, 前田恵里, 森健二郎, 味呑憲二郎
  • Industrial Property Rights Holder: 名古屋大学, 日東電工(株)
  • Industrial Property Number: 2012-016895
  • Filing Date: 2012-01-30
• [Patent(Industrial Property Rights)] Linker and Support for Solid Phase Synthesis of Nucleic Acid (2010)
  • Inventor(s): Y. Hayakawa, M. Tsukamoto
  • Industrial Property Rights Holder: 名古屋大学、日東電工(株)
  • Filing Date: 2010-10-20
  • Overseas
• [Patent(Industrial Property Rights)] 核酸固相合成用リンカー及び担体 (2010)
  • Inventor(s): 早川芳宏, 塚本眞幸, 森健二郎, 味呑憲二郎, 前田恵里, 小西達也
  • Industrial Property Rights Holder: 名古屋大学日東電工(株)
  • Filing Date: 2010-10-20
  • Overseas