Creation of agents that selectively photo-degrade certain proteins and oligosaccharides and its application to control of cell functions

• Project/Area Number: 26282212
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biomolecular chemistry
• Research Institution: Keio University
• Principal Investigator: TOSHIMA KAZUNOBU 慶應義塾大学, 理工学部, 教授 (60217502)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 生物活性分子 / 分子設計 / 合成 / タンパク / 糖 / 光分解 / 細胞 / 生体機能光制御分子 / アントラキノン / シアリルルイスA / ハイブリッド / がん細胞 / 抗体 / 生体機能分子 / 光制御 / 糖鎖 / 糖転移酵素 / 有機合成 / キノリン / ガラクトース / ノロウイルス / レクチン / 糖タンパク / 細胞毒性

Outline of Final Research Achievements

Several agents, that target-selectively photo-degrade certain disease-related proteins and oligosaccharides, were designed and synthesized. Furthermore, it was found the agents thus developed work not only in test tube but also in disease-related cells. From these studies, a new approach for the design of light-activated and molecular-targeted medicines has been established.

Research Products

• [Journal Article] Target-selective Photo-degradation of a Sialyl Lewis a (sLea) Conjugate and Photo-cytotoxicity Against sLea Positive Cancer Cells Using an Anthraquinone-antibody Hybrid (2016)
  • Author(s): D. Takahashi, T. Nagao, S. Sotokawa, K. Toshima
  • Journal Title: Medicinal Chemistry Communications Volume: 7 Issue: 6 Pages: 1224-1228
  • DOI: 10.1039/c6md00167j
  • Peer Reviewed
• [Journal Article] Total Synthesis of Aquayamycin (2016)
  • Author(s): S. Kusumi, H. Nakayama, T. Kobayashi, H. Kuriki, Y. Matsumoto, D. Takahashi, K. Toshima
  • Journal Title: Chemistry - A European Journal Volume: 22 Issue: 52 Pages: 18733-18736
  • DOI: 10.1002/chem.201604697
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Target-selective photo-degradation of AFP-L3 and selective photo-cytotoxicity against HuH-7 hepatocarcinoma cells using an anthraquinone-PhoSL hybrid (2016)
  • Author(s): M. Okuyama, H. Ueno, Y. Kobayashi, H. Kawagishi, D. Takahashi, K. Toshima
  • Journal Title: Chemical Communications Volume: 52 Issue: 10 Pages: 2169-2172
  • DOI: 10.1039/c5cc09542e
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Glycosylation of glycals using N-iodosuccinimide (NIS) and phosphorus compounds for syntheses of 2-iodo- and 2-deoxyglycosides (2015)
  • Author(s): T. Kimura, D. Takahashi, K. Toshima
  • Journal Title: Journal of Organic Chemistry Volume: 80 Issue: 19 Pages: 9552-9562
  • DOI: 10.1021/acs.joc.5b01542
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Systematic synthesis of low-molecular weight fucoidan derivatives and their effect on cancer cells (2015)
  • Author(s): A. Kasai, S. Arafuka, N. Koshiba, D. Takahashi, K. Toshima
  • Journal Title: Organic & Biomolecular Chemistry Volume: 13 Issue: 42 Pages: 10556-10568
  • DOI: 10.1039/c5ob01634g
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] One-pot transformation of N-succinyl chitosan to nitrogen-containing alkyl glycosides using an ionic liquid containing a protic acid (2015)
  • Author(s): M. Aoyagi, T. Kimura, A. Ohba, Y. Katayama, D. Takahashi, K. Toshima
  • Journal Title: Chemistry Letters Volume: 44 Issue: 11 Pages: 1467-1469
  • DOI: 10.1246/cl.150623
  • NAID: 130005108114
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Regioselective and 1,2-cis-α-stereoselective glycosylation utilizing glycosyl-acceptor-derived boronic ester catalyst (2015)
  • Author(s): A. Nakagawa, M. Tanaka, S. Hanamura, D. Takahashi, K. Toshima
  • Journal Title: Angewandte Chemie, International Edition Volume: 54 Issue: 37 Pages: 10935-10939
  • DOI: 10.1002/anie.201504182
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Chemical approach for target-selective degradation of oligosaccharides using photoactivatable organic molecules (2015)
  • Author(s): K. Toshima, D. Takahashi
  • Journal Title: Glycoconjugate Journal Volume: 34 Issue: 7 Pages: 475-482
  • DOI: 10.1007/s10719-015-9591-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Hierarchical CaCO3 Chromatography: A Stationary Phase Based on Biominerals (2015)
  • Author(s): Kosuke Sato, Yuya Oaki, Daisuke Takahashi, Kazunobu Toshima, Hiroaki Imai
  • Journal Title: Chem. Eur. J. Volume: 21 Issue: 13 Pages: 5034-5040
  • DOI: 10.1002/chem.201405724
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Chemical and biological evaluation of unusual sugars, alpha-aculosides, as novel Michael acceptor (2014)
  • Author(s): H. Ikeda, E. Kaneko, S. Okuzawa, D. Takahashi, K. Toshima
  • Journal Title: Organic & Biomolecular Chemistry Volume: 12 Issue: 44 Pages: 8832-8835
  • DOI: 10.1039/c4ob01877j
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A Solid-phase Affinity Labeling Method for Target-selective Isolation and Modification of Proteins (2014)
  • Author(s): Kuwahara, D.; Hasumi, T.; Kaneko, H.; Takahashi, D.; Toshima, K.
  • Journal Title: Chemical Communications Volume: 50 Issue: 98 Pages: 15601-15604
  • DOI: 10.1039/c4cc06783e
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Systematic synthesis of sulfated oligofucosides and their effect on breast cancer MCF-7 cells (2014)
  • Author(s): S. Arafuka, N. Koshiba, D. Takahashi, K. Toshima
  • Journal Title: Chemical Communications Volume: 50 Issue: 69 Pages: 9831-9834
  • DOI: 10.1039/c4cc03544e
  • Peer Reviewed
• [Journal Article] Photo-induced glycosylation using reusable organophotoacids (2014)
  • Author(s): R. Iwata, K. Uda, D. Takahashi, K. Toshima
  • Journal Title: Chemical Communications Volume: 50 Issue: 73 Pages: 10695-10698
  • DOI: 10.1039/c4cc04753b
  • Peer Reviewed
• [Journal Article] Photodegradation of amyloid β and reduction of its cytotoxicity to PC12 cells using porphyrin derivatives (2014)
  • Author(s): A. Hirabayashi, Y. Shindo, K. Oka, D. Takahashi, K. Toshima
  • Journal Title: Chemical Communications Volume: 50 Issue: 67 Pages: 9543-9546
  • DOI: 10.1039/c4cc03791j
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] アルツハイマー病原因物質アミロイドβを光分解する生体機能光制御分子の創製と応用 (2014)
  • Author(s): 平林歩、石田康則、高橋大介、戸嶋一敦
  • Journal Title: ケミカルバイオロジー Volume: 7 Pages: 2-5
• [Presentation] 還元糖を選択的に光分解するアントラキノン-ヒドラジドハイブリッドの創製とAGEs生成阻害への応用 (2017)
  • Author(s): 高城美智、高橋大介、戸嶋一敦
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 慶應義塾大学 （神奈川県、横浜市）
  • Year and Date: 2017-03-16
• [Presentation] セラノスティクスを指向したROS応答型蛍光分子-光感受性分子ハイブリッドの合成と機能評価 (2017)
  • Author(s): 高木亮馬、高橋大介、戸嶋一敦
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 應義塾大学 （神奈川県、横浜市）
  • Year and Date: 2017-03-16
• [Presentation] 光感受性分子-糖ハイブリッドによるグリコシダーゼの選択的光分解 (2017)
  • Author(s): 奥山真衣、高橋大介、戸嶋一敦
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 應義塾大学 （神奈川県、横浜市）
  • Year and Date: 2017-03-16
• [Presentation] アントラキノン-ヒドラジドハイブリッドによる還元糖の選択的光分解とAGEs 生成阻害への応用 (2016)
  • Author(s): 高城美智、高橋 大介、戸嶋一敦
  • Organizer: 日本ケミカルバイオロジー学会 第11 回年会
  • Place of Presentation: 京都テルサ（京都府、京都市）
  • Year and Date: 2016-06-15
• [Presentation] 光制御型酵素を指向したアントラキノン-酵素-ペプチドベクターハイブリッド分子の創製 (2016)
  • Author(s): 外川翔太、高橋 大介、戸嶋一敦
  • Organizer: 日本ケミカルバイオロジー学会 第11 回年会
  • Place of Presentation: 京都テルサ（京都府、京都市）
  • Year and Date: 2016-06-15
• [Presentation] 光制御型酵素を指向したアントラキノン-酵素-ペプチドハイブリッド分子の創製 (2016)
  • Author(s): 外川翔太、高橋 大介、戸嶋一敦
  • Organizer: 日本化学会第96 春季年会
  • Place of Presentation: 同志社大学京田辺キャンパス(京都府・京田辺市)
  • Year and Date: 2016-03-24
• [Presentation] Target-selective Photo-Degradation of AFP-L3 and Selective Photo-Cytotoxicity Against HuH-7 Hepatocarcinoma Cells Using An Anthraquinone-PhoSL Hybrid (2016)
  • Author(s): M. Okuyama, H. Ueno, Y. Kobayashi, H. Kawagishi, D. Takahashi, K. Toshima
  • Organizer: 4th National Tsing Hua University / Keio University Bilateral Symposium of Advanced Chemistry
  • Place of Presentation: 慶應義塾大学（神奈川県、横浜市）
  • Int'l Joint Research
• [Presentation] Target-selective photodegradation of oilgosaccharides in health and disease (2015)
  • Author(s): K. Toshima
  • Organizer: The 2015 International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Honolulu, ( USA)
  • Year and Date: 2015-12-15
  • Int'l Joint Research / Invited
• [Presentation] Target-selective photodegradation of proteins in chemical biology, The 2015 International Chemical Congress of Pacific Basin Societies (2015)
  • Author(s): K. Toshima
  • Organizer: Target-selective photodegradation of proteins in chemical biology, The 2015 International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Honolulu, ( USA)
  • Year and Date: 2015-12-15
• [Presentation] 肝がん関連糖タンパクAFP-L3を選択的に光分解するアントラキノン-PhoSL ハイブリッドの創製と肝がん細胞に対する効果 (2015)
  • Author(s): 奥山真衣、上野晴菜、小林夕香、河岸洋和、高橋大介、戸嶋一敦
  • Organizer: GlycoTOKYO 2015シンポジウム
  • Place of Presentation: 慶應義塾大学矢上キャンパス(神奈川県・横浜市)
  • Year and Date: 2015-10-24
• [Presentation] アントラキノン-PhoSLハイブリッド分子による肝がん関連糖タンパクAFP-L3の光分解及びヒト肝がん細胞HuH-7に対する効果 (2015)
  • Author(s): 上野晴菜、小林夕香、河岸洋和、高橋大介、戸嶋一敦
  • Organizer: 日本ケミカルバイオロジー学会 第10 回年会
  • Place of Presentation: 東北大学川内キャンパス(宮城県・仙台市)
  • Year and Date: 2015-06-10
• [Presentation] アントラキノン-糖ヌクレオチドハイブリッドによる糖転移酵素の光分解 (2015)
  • Author(s): 増田奏衣、高橋大介、戸嶋一敦
  • Organizer: 日本ケミカルバイオロジー学会 第10 回年会
  • Place of Presentation: 東北大学川内キャンパス(宮城県・仙台市)
  • Year and Date: 2015-06-10
• [Presentation] ノロウイルス関連タンパクVP1を光分解するアントラキノン‐H抗原糖鎖ハイブリッドの創製 (2015)
  • Author(s): 志村拓海、大久保聡太、上野晴菜、高橋大介、戸嶋一敦
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学(千葉県船橋市）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] アントラキノン-ハルミンハイブリッドによるアルツハイマー病関連タンパクDYRK1Aの選択的光分解 (2015)
  • Author(s): 奥山真衣、増田奏衣、高橋大介、戸嶋一敦
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学(千葉県船橋市）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 糖質および抗生物質の合成と生体機能光制御分子の創製に関する研究 (2015)
  • Author(s): 戸嶋一敦
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学(千葉県船橋市）
  • Year and Date: 2015-03-26 – 2015-03-29
  • Invited
• [Presentation] 標的生体高分子を選択的に光分解する化学的手法の開発と生物学的応用 (2014)
  • Author(s): 戸嶋一敦
  • Organizer: 国際高等研究所研究プロジェクト「分子基盤に基づく生体機能への揺らぎとダイナミックネットワークの解明」2014年度第1回研究プログラム
  • Place of Presentation: 国際高等研究所(京都府木津川市）
  • Year and Date: 2014-12-14 – 2014-12-15
  • Invited
• [Presentation] Total synthesis of vineomycin B2 : Application of glycosylation method using 2,3-unsaturated sugars to natural products synthesis (2014)
  • Author(s): K. Toshima
  • Organizer: Vietnam Malaysia International Chemical Congress (VMICC2014)
  • Place of Presentation: ハノイ(ベトナム）
  • Year and Date: 2014-11-07 – 2014-11-09
  • Invited
• [Presentation] アントラキノン－抗体ハイブリッドによるシアリルルイスA糖鎖の選択的光分解 (2014)
  • Author(s): 長尾高志、高橋大介、戸嶋一敦
  • Organizer: 日本ケミカルバイオロジー学会第9回年会
  • Place of Presentation: 大阪大学(大阪府豊中市）
  • Year and Date: 2014-06-11 – 2014-06-13
• [Book] 糖鎖の新機能開発・応用ハンドブック (2015)
  • Author(s): 高橋大介、戸嶋一敦
  • Total Pages: 3
  • Publisher: エヌ・ティー・エス
• [Remarks] http://www.applc.keio.ac.jp/~toshima/index.html
• [Remarks] 戸嶋研究室（分子生命化学研究室）
  • URL: http://www.applc.keio.ac.jp/~toshima/
• [Remarks] http://www.applc.keio.ac.jp/~toshima/