Development of covalent ligands to modulate CD1d protein function

• Project/Area Number: 26882036
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Biomolecular chemistry
• Research Institution: Keio University
• Principal Investigator: INUKI SHINSUKE 慶應義塾大学, 理工学部, 助教 (70736272)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 免疫機能解析 / 生物有機化学 / ケミカルバイオロジー / 相互作用解析 / 分子動力学計算 / 免疫調節 / 脂質抗原受容体 / 共有結合 / 有機合成化学

Outline of Final Research Achievements

We focused on CD1d protein that can control the activation of natural killer T (NKT) cells through the presentation of self and foreign lipids, and planned to develop selective covalent ligands toward CD1d in order to enable the functional analysis and the modulation of CD1d. Based on the known CD1d ligand, α-GalCer, we designed novel covalent ligands containing an amide group as a linker. Some of the designed ligands showed the higher affinities to CD1d, and increased the cytokine production compared with α-GalCer.

Research Products

• [Journal Article] Efficient synthesis of (-)-hanishin, (-)-longamide B, and (-)-longamide B Methyl Ester via piperazinone formation with 1,2-cyclic sulfamidates (2016)
  • Author(s): Shiokawa, Z., Inuki, S., Fukase, K., Fujimoto, Y.
  • Journal Title: Synlett Volume: 27 Issue: 04 Pages: 616-620
  • DOI: 10.1055/s-0035-1560988
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Visible-light-mediated decarboxylative benzoyloxylation of -hydroxy amino acids and its application to synthesis of functional 1,2-amino alcohol derivatives (2015)
  • Author(s): Inuki, S., Sato, K., Fujimoto, Y.
  • Journal Title: Tetrahedron Lett. Volume: 56 Issue: 42 Pages: 5787-5790
  • DOI: 10.1016/j.tetlet.2015.09.012
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] CD1dの脂質認識部位への高親和性を指向した新規リガンドの創製研究 (2016)
  • Author(s): 井貫晋輔、相羽俊彦、平田菜摘、市原収、吉留大輔、日下裕規、喜多俊介、前仲勝実、深瀬浩一、藤本ゆかり
  • 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] 免疫活性化能を示すTLR2リガンド・リポペプチド標識体合成および解析 (2016)
  • Author(s): 荒井洋平、太田一平、横山康平、フォンチ、樺山一哉、井貫晋輔、深瀬浩一、藤本ゆかり
  • Organizer: 日本化学会第96春季年会
  • Place of Presentation: 同志社大学（京都府・京田辺市）
  • Year and Date: 2016-03-24
• [Presentation] 光反応を利用したデオキシアミノ糖類の合成研究 (2016)
  • Author(s): 佐藤啓介、福山高英、柳日馨、井貫晋輔、藤本ゆかり
  • Organizer: 日本化学会第96春季年会
  • Place of Presentation: 同志社大学（京都府・京田辺市）
  • Year and Date: 2016-03-24
• [Presentation] Synthesis and immunomodulatory activity of unique protozoal inositol phospholipids containing long fatty acids (2016)
  • Author(s): Toshihiko Aiba, Sae Suehara, Hannah Bernin, Hanna Lotter, Shinsuke Inuki, Koichi Fukase, Yukari Fujimoto
  • Organizer: The 8th Takeda Science Foundation Symposium on PharmaSciences
  • Place of Presentation: 武田薬品工業研修所(大阪府・吹田市）
  • Year and Date: 2016-01-21
  • Int'l Joint Research
• [Presentation] Decarboxylative Functionalization of β-Hydroxy Amino Acids via Photoredox Catalysis and Its Application to Synthesis of Functional 1,2-Amino Alcohol Derivatives (2015)
  • Author(s): Shinsuke Inuki, Keisuke Sato, Yukari Fujimoto
  • Organizer: 2015 International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Honolulu（USA）
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Synthetic Studies on Funiculosin (2015)
  • Author(s): Keisuke Sato, Shinsuke Inuki, Yukari Fujimoto
  • Organizer: 2015 International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Honolulu（USA）
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Fluorescence-labeled lipopeptides as molecular probes for TLR2 (2015)
  • Author(s): Yohei Arai, Yuki Kawahara, Kouhei Yokoyama, Shinsuke Inuki, Kazuya Kabayama, Koichi Fukase, Yukari Fujimoto
  • Organizer: 2015 International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Honolulu（USA）
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Synthesis of inositol phospholipids from Ascaris Suum using regioselective phosphorylation (2015)
  • Author(s): Sae Suehara, Toshihiko Aiba, Shou Nakagawa, Masaki Sato, Yuuki Maekawa, Toshiaki Murai, Koichi Fukase, Shinsuke Inuki, Yukari Fujimoto
  • Organizer: 2015 International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Honolulu（USA）
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Synthetic Studiy on Cardiolipin Containing Cyclopropane Fatty Acids (2015)
  • Author(s): Shunichi Ishibashi, Shinsuke Inuki, Yukari Fujimoto
  • Organizer: 2015 International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Honolulu（USA）
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Decarboxylative Functionalization of β-Hydroxy Amino Acids via Photoredox Catalysis and Its Application to Synthesis of Functional 1,2-Amino Alcohol Derivatives (2015)
  • Author(s): Shinsuke Inuki, Keisuke Sato, Yukari Fujimoto
  • Organizer: The 13th International Kyoto Conference on New Aspects of Organic Chemistry
  • Place of Presentation: リーガロイヤルホテル京都（京都府・京都市）
  • Year and Date: 2015-11-09
  • Int'l Joint Research
• [Presentation] Synthesis and Immunoregulatory Activity of Lipophosphoglycans as NKT Cell Modulator (2015)
  • Author(s): Toshihiko Aiba, Sae Suehara, Hannah Bernin, Hanna Lotter, Shinsuke Inuki, Koichi Fukase, Yukari Fujimoto
  • Organizer: The 13th International Kyoto Conference on New Aspects of Organic Chemistry
  • Place of Presentation: リーガロイヤルホテル京都（京都府・京都市）
  • Year and Date: 2015-11-09
  • Int'l Joint Research
• [Presentation] Photoredox触媒を用いたデオキシアミノ糖類の合成研究 (2015)
  • Author(s): 佐藤啓介、井貫晋輔、藤本ゆかり
  • Organizer: GlycoTOKYO
  • Place of Presentation: 慶應義塾大学（神奈川県・横浜市）
  • Year and Date: 2015-10-24
• [Presentation] Ascaris suum由来イノシトールリン脂質の合成研究 (2015)
  • Author(s): 末原紗英、相羽俊彦、前川侑輝、村井利昭、深瀬浩一、井貫晋輔、藤本ゆかり
  • Organizer: GlycoTOKYO
  • Place of Presentation: 慶應義塾大学（神奈川県・横浜市）
  • Year and Date: 2015-10-24
• [Presentation] Gal(α1-6)Gal構造を含有する糖脂質の合成研究 (2015)
  • Author(s): 柏原瑛美、相羽俊彦、井貫晋輔、藤本ゆかり
  • Organizer: GlycoTOKYO
  • Place of Presentation: 慶應義塾大学（神奈川県・横浜市）
  • Year and Date: 2015-10-24
• [Presentation] 自然免疫受容体TLR2リガンドの蛍光標識体合成と解析 (2015)
  • Author(s): 荒井洋平、横山康平、フォンチ、樺山一哉、井貫晋輔、深瀬浩一、藤本ゆかり
  • Organizer: 第5回 CSJ化学フェスタ2015
  • Place of Presentation: タワーホール船堀（東京都・江戸川区）
  • Year and Date: 2015-10-13
• [Presentation] Synthesis and Biological Activity of Inositol Phospholipid as NKT Cell Modulator (2015)
  • Author(s): Toshihiko Aiba, Sae Suehara, Hannah Bernin, Hanna Lotter, Shinsuke Inuki, Koichi Fukase, Yukari Fujimoto
  • Organizer: 23rd International Symposium on Glycoconjugates
  • Place of Presentation: Split（Croatia）
  • Year and Date: 2015-09-15
  • Int'l Joint Research
• [Presentation] 自然免疫受容体リガンドの細胞内動態解析に向けて (2015)
  • Author(s): 横山康平、河原佑紀、Qi Feng、荒井洋平、井貫晋輔、藤本ゆかり、樺山一哉、深瀬浩一
  • 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（宮城県・仙台市）
  • Year and Date: 2015-06-10
• [Presentation] Photoredox触媒を用いた光学活性1,2-アミノアルコール類の合成法開発 (2015)
  • Author(s): 井貫晋輔、藤本ゆかり
  • Organizer: 第14回新規素材探索研究会
  • Place of Presentation: 新横浜フジビューホテル（神奈川県・横浜市）
  • Year and Date: 2015-06-05
• [Presentation] Entamoeba histolytica由来糖イノシトールリン脂質の合成と免疫調節活性 (2015)
  • Author(s): 相羽俊彦、末原紗英、Bernin Hannah、Lotter Hanna、井貫晋輔、深瀬浩一、藤本ゆかり
  • Organizer: 第14回新規素材探索研究会
  • Place of Presentation: 新横浜フジビューホテル（神奈川県・横浜市）
  • Year and Date: 2015-06-05
• [Presentation] 位置選択的リン酸化反応を用いたAscaris suum由来イノシトールリン脂質の合成研究 (2015)
  • Author(s): 末原紗英、相羽俊彦、中川翔、佐藤昌紀、前川侑輝、村井利昭、深瀬浩一、井貫晋輔、藤本ゆかり
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学（千葉・船橋）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 免疫調節作用を有する原虫由来イノシトールリン脂質の合成と生物活性 (2015)
  • Author(s): 相羽俊彦、末原紗英、佐藤昌紀、田中慎二、北村雅人、BERNIN HANNAH、LOTTER HANNA、井貫晋輔、深瀬浩一、藤本ゆかり
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学（千葉・船橋）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Remarks] 慶應義塾大学理工学部化学科 生体分子化学研究室ホームページ
  • URL: http://www.chem.keio.ac.jp/~fujimoto-lab/
• [Patent(Industrial Property Rights)] 化合物又はその塩、ナチュラルキラーＴ細胞活性化剤、及び医薬組成物 (2016)
  • Inventor(s): 井貫晋輔、相羽俊彦、平田菜摘、藤本ゆかり
  • Industrial Property Rights Holder: 井貫晋輔、相羽俊彦、平田菜摘、藤本ゆかり
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-03-22