Development of new channelrhodpsin having the long conjugated chromophore

• Project/Area Number: 26450146
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bioorganic chemistry
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: WADA Akimori 神戸薬科大学, 薬学部, 教授 (80158683)
• Co-Investigator(Renkei-kenkyūsha): SHICHIDA Yoshinori 京都大学, 大学院・理学研究科, 教授 (60127090)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: チャネルロドプシン / 発色団 / 長い共役系 / 赤色光 / レチナール / ケミカルバイオロジー / 共役系 / 長波長吸収 / オプトジェネティクス / チャンネルロドプシン

Outline of Final Research Achievements

Optogenetics is a powerful new tool, which allows control of neuronal activity by light. Channelrhodopsins are light-gated cation channels and have been used for optogenetics. In order to construct a new type of channelrhodopsin having the chromophore responding to the longer wavelength, we prepared the novel retinal analogs with double bond-elongated at the Schiff base, side chain or cyclohexene ring of retinal and 3,4-dehyrdoretinal.All analogs synthesized here bound to apo-protein to afford the new channelrhodopsins. Although the red shift values of ramuda max were only 10-20 nm, these channelrhodopsins exhibited the half of absorption maximum at about 560-580 nm, which were about 50-80 nm red shifted than that of native channelrhodopsin.

Research Products

• [Journal Article] Alternative Formation of Red-Shifted Channelrhodopsins: Noncovalent Incorporation with Retinal-Based Enamine-Type Schiff Bases and Mutated Channelopsin (2017)
  • Author(s): T. Okitsu
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 65 Issue: 4 Pages: 356-358
  • DOI: 10.1248/cpb.c17-00054
  • NAID: 130005529782
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed
• [Journal Article] Solid-state NMR structural study of retinal-binding pocket in sodium ion pump rhodopsin. (2017)
  • Author(s): Arisu Shigeta, Shota Ito, Keiichi Inoue, Takashi Okitsu, Akimori Wada, Hideki Kandori, Izuru Kawamura*
  • Journal Title: Biochemistry Volume: 56 Issue: 4 Pages: 543-550
  • DOI: 10.1021/acs.biochem.6b00999
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Convergent Synthesis of Dronedarone, an Antiarrhythmic Agent (2016)
  • Author(s): Okitsu, T.; Ogasahara, M.; Wada, A.
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 64 Issue: 8 Pages: 1149-1153
  • DOI: 10.1248/cpb.c16-00237
  • NAID: 130005253909
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Modulation of thermal noise and spectral sensitivity in Lake Baikal cottoid fish rhodopsins (2016)
  • Author(s): Luk, H. L.; Bhattacharyya, N.; Montisci, F.; Morrow, J. M.; Melaccio, F.; Wada, A.; Sheves, M.; Fanelli, F.; Chang, B. S. W.; Olivucci, M.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 38425-38425
  • DOI: 10.1038/srep38425
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Anti-Oxidative Activity of Mytiloxanthin, a Metabolite of Fucoxanthin in Shellfish and Tunicates (2016)
  • Author(s): Maoka, T.; Nishino, A.; Yasui, H.; Yamano, Y.; Wada, A.
  • Journal Title: Mar. Drugs Volume: 14 Issue: 5 Pages: 93-93
  • DOI: 10.3390/md14050093
  • Peer Reviewed
• [Journal Article] Oxidative Metabolites of Lycopene and -Carotene in Gac (Momordica cochinchinensis) (2015)
  • Author(s): Maoka, T.; Yamano, Y.; Wada, A.; Etho, T.; Terada, Y.; Tokuda, H.; Nishino, H
  • Journal Title: J. Agric. Food Chem. Volume: 63 Issue: 5 Pages: 1622-1630
  • DOI: 10.1021/jf505008d
  • Peer Reviewed
• [Journal Article] Total synthesis of gobiusxanthin stereoisomers and their application to determination of absolute configurations of natural products: revision of reported absolute configuration of epigobiusxanthin (2015)
  • Author(s): Yamano, Y.; Ematsu, K.; Kurimoto, H.; Maoka, T.; Wada, A.
  • Journal Title: Mar. Drugs Volume: 13 Issue: 1 Pages: 159-172
  • DOI: 10.3390/md13010159
  • Peer Reviewed
• [Journal Article] Stereocontrolled First Total Syntheses of Salmoxanthin and Deepoxysalmoxanthin (2015)
  • Author(s): Yamano, Y.; Eno, K.; Hikita, Y.; Kurimoto, H.; Wada, A.
  • Journal Title: Curr. Org. Synth. Volume: 12 Issue: 2 Pages: 180-188
  • DOI: 10.2174/1570179411999141106102507
  • Peer Reviewed
• [Journal Article] Identical hydrogen-bonding strength of the retinal Schiff base between primate green- and red-sensitive pigments: New insight into color tuning mechanism (2015)
  • Author(s): K. Katayama, T. Okitsu, H. Imai, A. Wada, H. Kandori*
  • Journal Title: J. Phys. Chem. Lett Volume: 6 Issue: 7 Pages: 1130-1133
  • DOI: 10.1021/acs.jpclett.5b00291
  • Peer Reviewed
• [Journal Article] Characterization of photo-intermediates in the photo-reaction pathways of a bacteriorhodopsin Y185F mutant using in situ photo-irradiation solid-state NMR spectroscopy (2015)
  • Author(s): Kyosuke Oshima, Aris Shigeta, Yoshiteru Makino, Izuru Kawamura, Takashi Okitsu, Akimori Wada, Satoru Tuzi, Tetsuo Iwasa, Akira Naito
  • Journal Title: Photochem. Photobiol. Sci. Volume: 14 Issue: 9 Pages: 2015-2015
  • DOI: 10.1039/c5pp00154d
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Origin of the low thermal isomerization rate of rhodopsin chromophore (2015)
  • Author(s): Yanagawa, M.; Kojima, K.; Yamashita, T.; Iwamoto, Y.; Matsuyama, T.; Nakanishi, K.; Yamano, Y.; Wada, A.; Sako, Y.; Shichida, Y.
  • Journal Title: Sci. Rep. Volume: 5 Issue: 1 Pages: 11081-11081
  • DOI: 10.1038/srep11081
  • NAID: 120005690204
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ligand-induced population shift leads to the activation of rhodopsin, a G-protein coupled receptor (2014)
  • Author(s): Maeda, R., Hiroshima, M., Yamashita, T., Wada, A., Nishimura, S., Sako, Y., Shichida, Y., and Imamoto, Y
  • Journal Title: Biophys. J Volume: 106 (4) Issue: 4 Pages: 915-924
  • DOI: 10.1016/j.bpj.2014.01.020
  • Peer Reviewed
• [Journal Article] Inhibition of lysine-specific demethylase 1 by the acyclic diterpenoid geranylgeranoic acid and its derivatives. (2014)
  • Author(s): Sakane C, Okitsu T, Wada A, Sagami H, Shidoji Y.
  • Journal Title: Biochem Biophys Res Commun. Volume: 444 Issue: 1 Pages: 24-29
  • DOI: 10.1016/j.bbrc.2013.12.144
  • Peer Reviewed
• [Journal Article] Synthesis of (3S,3S')- and meso-stereoisomers of alloxanthin and determination of absolute configuration of alloxanthin isolated from aquatic animals (2014)
  • Author(s): Yamano, Y.; Maoka, T.; Wada, A.
  • Journal Title: Mar. Drugs Volume: 12 Issue: 5 Pages: 2626-2632
  • DOI: 10.3390/md12052623
  • Peer Reviewed
• [Journal Article] Iodocyclization of Ethoxyethyl Ethers to Ynamides: An Immediate Construction to Benzo[b]furans (2014)
  • Author(s): Okitsu, T.; Nakata, K.; Nishigaki, K.; Michioka, N.; Karatani, M.; Wada, A.
  • Journal Title: J. Org. Chem. Volume: 79 Pages: 5914-5920
  • Peer Reviewed
• [Journal Article] Color Discriminating Retinal Configurations of Sensory Rhodopsin I by Photo-Irradiation Solid State NMR Spectroscopy. (2014)
  • Author(s): H. Yomonda, Y. Makino, Y. Tomonaga, T. Hidaka, I. Kawamura*, T. Okitsu, A. Wada, Y. Sudo*, A. Naito*.
  • Journal Title: Angew. Chem. Int. Ed. Volume: 53 Issue: 27 Pages: 6960-6964
  • DOI: 10.1002/anie.201309258
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ビタミンA誘導体を用いた生物有機化学的研究 (2014)
  • Author(s): 和田 昭盛
  • Journal Title: ビタミン Volume: 88 Pages: 72-81
  • NAID: 110009805253
  • Peer Reviewed
• [Presentation] レチナール環構造に共役系を導入したアナログの合成とタンパク質オプシンとの相互作用 (2016)
  • Author(s): 和田昭盛、山野由美子、沖津貴志、山下高廣、今元泰、七田芳則
  • Organizer: 日本レチノイド研究会第２７学術集会
  • Place of Presentation: 町田
  • Year and Date: 2016-10-22
• [Presentation] 共役したクロメン環を有するレチナールアナログの合成研究 (2016)
  • Author(s): 神崎さくら子、石井菜紬子、沖津貴志、和田昭盛
  • Organizer: 日本ビタミン学会第６８回大会
  • Place of Presentation: 富山
  • Year and Date: 2016-06-18
• [Presentation] Iodonium-mediated dearomative cyclization/Diels-Alder tandem of a chiral ynamide toward diastereoselective construction of bridgehead-spiro system (2015)
  • Author(s): Okitsu, T.; Murai, C.; Wada, A.
  • Organizer: Pacifichem 2015
  • Place of Presentation: Honolulu/USA
  • Year and Date: 2015-12-19
  • Int'l Joint Research
• [Presentation] Lycopeneの新規酸化代謝物、lycopene-5,6-diol立体異性体の全合成 (2015)
  • Author(s): 山野 由美子、西山 裕也、青木 敦志、和田 昭盛
  • Organizer: 第41回反応と合成の進歩シンポジウム
  • Place of Presentation: 東大阪
  • Year and Date: 2015-10-26
• [Presentation] イナミドの求電子性が促進する6-endo-dig環化：ピリダジン類の制御合成 (2015)
  • Author(s): 沖津 貴志、森澤 祐介、本村 映人、和田 昭盛
  • Organizer: 第41回反応と合成の進歩シンポジウム
  • Place of Presentation: 東大阪
  • Year and Date: 2015-10-26
• [Presentation] Preparation of New ChR with One Double Bond-elongated 3,4-Dehydroretinals (2015)
  • Author(s): Wada, A.; Okitsu, T.; Yamano, Y.; Kobayashi, Y.; Ishizuka, T.; Yawo, H.; Matsuyama, T.; Yamashiya, T.; Imamoto, Y.; Shichida, Y.
  • Organizer: The 3rd International Conference on Retinoids
  • Place of Presentation: Gifu/Japan
  • Year and Date: 2015-10-21
  • Int'l Joint Research
• [Presentation] ガックより単離されたlycopene-5,6-diolおよびγ-carotene-5’,6’-diolの立体異性体の合成とHPLC分離条件の確立 (2015)
  • Author(s): 山野 由美子、西山 裕也、青木 敦志、和田 昭盛、眞岡 孝至
  • Organizer: 第29回カロテノイド研究談話会
  • Place of Presentation: 八王子
  • Year and Date: 2015-09-04
• [Presentation] 3-メチレン-4-アミド-1,2-ジアゼチジンの求核的開環反応 (2014)
  • Author(s): 沖津 貴志、小林 恵子、吉田 淳美、吉田 裕司、和田 昭盛
  • Organizer: 第40回反応と合成の進歩シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2014-11-10
• [Presentation] β-ジケトン構造を有するアセチレンカロテノイドmytiloxanthinの立体選択的全合成 (2014)
  • Author(s): 山野 由美子、大畑 雅裕、和田 昭盛
  • Organizer: 第40回反応と合成の進歩シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2014-11-10
• [Presentation] 7-ヒドロキシレチノイン酸の合成と生物活性 (2014)
  • Author(s): 和田 昭盛、山野 由美子、笠原 奈那子、脇本 友絵、中川 公恵、岡野 登志夫
  • Organizer: 日本レチノイド研究会第25回学術集会
  • Place of Presentation: 秋田
  • Year and Date: 2014-10-11
• [Presentation] Preparation of Red-Shifted PSB of Retinal Having Enamine Structure (2014)
  • Author(s): Wada, A.; Okitsu, T.; Futamura, N.; Niimi, Y.; Ishizuka, T.; Yawo, H.; Matsuyama Hoyos, T.; Yamashiya, T.; Shichida, Y.
  • Organizer: 16th International Conference on Retinal Proteins
  • Place of Presentation: Nagahama
  • Year and Date: 2014-10-05 – 2014-10-10
• [Presentation] イナミドのヨード環化反応を利用したベンゾフランの即時合成 (2014)
  • Author(s): 沖津 貴志、中田 康平、西垣 賢志、道岡 直幸、柄谷 光章、和田 昭盛
  • Organizer: 第17回ヨウ素学会シンポジウム
  • Place of Presentation: 千葉
  • Year and Date: 2014-09-19
• [Presentation] mytiloxanthinの立体選択的全合成 (2014)
  • Author(s): 山野 由美子、大畑 雅裕、和田 昭盛
  • Organizer: 第28回カロテノイド研究談話会
  • Place of Presentation: 金沢
  • Year and Date: 2014-09-05
• [Presentation] ガックに含まれる-Caroteneの酸化代謝産物について (2014)
  • Author(s): 眞岡 孝至、山野 由美子、和田 昭盛
  • Organizer: 第28回カロテノイド研究談話会
  • Place of Presentation: 金沢
  • Year and Date: 2014-09-05
• [Presentation] 3-メチレン-4-アミド-1,2-ジアゼチジンへのアリルシランの求核的開環反応 (2014)
  • Author(s): 沖津 貴志、小林 恵子、吉田 淳美、和田 昭盛
  • Organizer: 第34回有機合成若手セミナー
  • Place of Presentation: 神戸
  • Year and Date: 2014-08-05