Photocontrol of NO and H2S treatment as signaling molecules and biological applications

• Project/Area Number: 25293028
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Nagoya City University
• Principal Investigator: Nakagawa Hidehiko 名古屋市立大学, 薬学研究科(研究院), 教授 (80281674)
• Co-Investigator(Renkei-kenkyūsha): Ieda Naoya 名古屋市立大学, 大学院薬学研究科, 助教 (00642026) ; Miyata Naoki 名古屋市立大学, 大学院薬学研究科, 特任教授 (50114674)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2015: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
• Keywords: ケミカルバイオロジー / ケージド化合物 / 薬学 / 有機化学 / 光スイッチ

Outline of Final Research Achievements

A caged NO molecule, Flu-DNB-DB, was developed and applied for cultured cells. When the cells loaded with Flu-DNB-DB was irradiated with near infrared femto-second pulse laser, NO release within the irradiated cells was observed. Another caged NO molecule, Rol-DNB, was developed. Rol-DNB was found to release NO upon photo irradiation at the range of 530-590 nm, yellow-green light, with spatiotemporal resolution. Rol-DNB was also found to be localized to mitochondria within the cells. It was demonstrated that NO release from Rol-DNB upon yellow-green light resulted in the enhancement of mitochondrial fragmentation depending on Drp-1 activation.

Research Products

• [Journal Article] A double bond-conjugated dimethylnitrobenzene-type photolabile nitric oxide donor with improved two-photon cross section (2015)
  • Author(s): 1.N. Ieda, K. Hishikawa, K. Eto, K. Kitamura, M. Kawaguchi, T. Suzuki, K. Fukuhara, N. Miyata, T. Furuta, J. Nabekura, H. Nakagawa
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 25 Issue: 16 Pages: 3172-3175
  • DOI: 10.1016/j.bmcl.2015.05.095
  • Peer Reviewed / Open Access
• [Journal Article] Profiling and relative quantification of multiply nitrated and oxidized fatty acids (2015)
  • Author(s): Milic I, Griesser E, Vemula V, Ieda N, Nakagawa H, Miyata N, Galano J-M, Oger C, Durand T, Fedorova F
  • Journal Title: Anal. Bioanal. Chem. Volume: 407 Issue: 19 Pages: 5587-5602
  • DOI: 10.1007/s00216-015-8766-3
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Development of Photo-controllable Hydrogen Sulfide Donor Applicable in Live Cells (2015)
  • Author(s): Naoki Fukushima, Naoya Ieda, Mitsuyasu Kawaguchi, Kiyoshi Sasakura, Tetsuo Nagano, Kenjiro Hanaoka, Naoki Miyata, Hidehiko Nakagawa
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 25 Issue: 2 Pages: 175-178
  • DOI: 10.1016/j.bmcl.2014.11.084
  • Peer Reviewed / Open Access
• [Journal Article] Synthesis of a photocontrollable hydrogen sulfide donor using ketoprofenate photocages (2014)
  • Author(s): Naoki Fukushima, Hidehiko Nakagawa, et al.
  • Journal Title: Chem. Commun Volume: 50 Issue: 5 Pages: 587-589
  • DOI: 10.1039/c3cc47421f
  • Peer Reviewed
• [Journal Article] hotomanipulation of Vasodilation with a Blue-Light-Controllable Nitric Oxide Releaser (2014)
  • Author(s): Naoya Ieda, Hidehiko Nakagawa, et al.
  • Journal Title: J. Am. Chem. Soc. Volume: 136 Issue: 19 Pages: 7085-7091
  • DOI: 10.1021/ja5020053
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Visible light-induced nitric oxide release from a novel nitrobenzene derivative cross-conjugated with a coumarin fluorophore (2014)
  • Author(s): Kai Kitamura, Hidehiko Nakagawa et al.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 24 Issue: 24 Pages: 5660-5662
  • DOI: 10.1016/j.bmcl.2014.10.075
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Fine spatiotemporal control of nitric oxide release by infrared pulse-laser irradiation of a photo-labile donor (2013)
  • Author(s): Hidehiko Nakagawa, Kazuhiro Hishikawa, Kei Eto, et al.
  • Journal Title: ACS. Chem. Biol. Volume: 8 Issue: 11 Pages: 2493-2500
  • DOI: 10.1021/cb400361m
  • Peer Reviewed
• [Journal Article] A Reductant-Resistant and Metal-Free Fluorescent Probe for Nitroxyl Applicable to Living Cells (2013)
  • Author(s): Kodai Kawai, Naoya Ieda, Hidehiko Nakagawa, et al.
  • Journal Title: J. Am. Chem. Soc. Volume: 135 Issue: 34 Pages: 12690-12696
  • DOI: 10.1021/ja404757s
  • Peer Reviewed
• [Presentation] Two-photon uncaging of photo-NO releasers and vasodilation in living mouse brain (2015)
  • Author(s): Hidehiko Nakagawa
  • Organizer: Pacifichem2015
  • Place of Presentation: Honolulu, HI, USA
  • Year and Date: 2015-12-15
  • Int'l Joint Research / Invited
• [Presentation] Development of Blue-Light-Controllable Nitric Oxide Releaser and its Biological Application (2015)
  • Author(s): Naoya Ieda, Hidehiko Nakagawa, et al.
  • Organizer: SFRBM2015
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2015-11-18
  • Int'l Joint Research
• [Presentation] 光で制御する一酸化窒素・活性酸素投与法の開発と応用 (2015)
  • Author(s): 中川秀彦
  • Organizer: 第68回日本酸化ストレス学会学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2015-06-11
  • Invited
• [Presentation] Caged compounds for gaseous mediators, nitric oxide and hydrogen sulfide, and their biological applications (2015)
  • Author(s): Hidehiko Nakagawa
  • Organizer: 3rd Bioscience and Biotechnology International Symposium
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2015-01-14
  • Invited
• [Presentation] Mitochondria-targeting Nitric Oxide Releasers Controllable with Visible Light (2014)
  • Author(s): Kai Kitamura, Hidehiko Nakagawa, et al.
  • Organizer: ICBS2014
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-11-17 – 2014-11-19
• [Presentation] Photo-inducible hydrogen sulfide releaser using ketoprofenate photocages (2014)
  • Author(s): Hidehiko Nakagawa, et al.
  • Organizer: Third International Conference on H2S Biology and Medicine
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2014-06-04 – 2014-06-06
• [Presentation] 光解除性保護基を用いた光制御型硫化水素供与化合物の合成と機能評価 (2014)
  • Author(s): 福島直樹、中川秀彦ほか
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Remarks] 名古屋市立大学薬学部・大学院薬学研究科薬化学分野
  • URL: http://www.phar.nagoya-cu.ac.jp/hp/ykg/Yakka/index.html
• [Remarks] 名古屋市立大学大学院薬学研究科薬化学分野
  • URL: http://www.phar.nagoya-cu.ac.jp/hp/ykg/Yakka/index.html
• [Patent(Industrial Property Rights)] N-ニトロソアニリン誘導体、並びに、それを用いたNO発生剤及びNOの発生方法 (2013)
  • Inventor(s): 家田直弥、中川秀彦
  • Industrial Property Rights Holder: 名古屋市立大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-234477
  • Filing Date: 2013-11-12