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Development of novel glycolipids] which activate natural killer T cells to induce antitumor acivity

Research Project

Project/Area Number 20790108
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Drug development chemistry
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

TASHIRO Takuya  The Institute of Physical and Chemical Research, 免疫制御研究グループ, 研究員 (20339104)

Co-Investigator(Renkei-kenkyūsha) MORI Kenji  東京大学名誉教授, 理化学研究所, 研究顧問 (20011843)
HIROKAWA Takatsugu  独立行政法人 産業技術総合研究所, 分子設計チーム (20357867)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsalpha-GalCer / CD1d / carba-galactose / cyclitol / glycosphingolipid / IFN-gamma / KRN7000 / NKT cell / aloha-carba-GalCer / CDld / RCAI-56 / サイトカイン / ナチュラルキラーT細胞 / RCAI-61
Research Abstract

KRN7000, an alpha-Galactosylceramide, stimulates natural killer T cells to induce antitumor activity. RCAI-56, a carba-galactose analog of KRN7000, induces a larger amount of IFN-gamma production than KRN7000. Based on the X-ray crystallographic analysis, further structure-activity relationship study was performed on RCAI-56, and it was found that RCAI-59, the 5a-deoxycyclitol analog of KRN7000, and its relatives induce potent IFN-gamma production.

Report

(3 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • Research Products

    (30 results)

All 2011 2010 2009 2008

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (9 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Induction of Th1-biased cytokine production by 〓-carba-GalCer, a neoglycolipid ligand for NKT cells2010

    • Author(s)
      Takuya Tashiro(15人中1番目)
    • Journal Title

      Int. Immunol. 22

      Pages: 319-328

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant V〓14-J〓18 TCR〓 gene2010

    • Author(s)
      Takuya Tashiro(15人中8番目)
    • Journal Title

      Blood 115

      Pages: 230-237

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The specialized iNKT cell system recognizes glycolipid antigens and bridges the innate and acquired immune systems with potential applications for cancer therapy2010

    • Author(s)
      Takuya Tashiro(5人中2番目)
    • Journal Title

      Int. Immunology 22

      Pages: 1-6

    • NAID

      10027390882

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The specialized iNKT cell system recognizes glycolipid antigens and bridges the innate and acquired immune systems with potential applications for cancer therapy2010

    • Author(s)
      Masaru Taniguchi
    • Journal Title

      International Immunology 22

      Pages: 1-6

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of Th1-biased cytokine production by α-carba-GalCer, a neoglycolipid ligand of NKT cells2010

    • Author(s)
      Takuya Tashiro
    • Journal Title

      International Immunology 22(in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pheromone synthesis Part 243 : Synthesis and biological evaluation of(3R, 13R, 1'S)-1'-ethyl-2'-methylpropyl 3, 13-dimethylpentadecanoate, the major component of the sex pheromone of Paulownia bagworm, Clania variegata, and its stereoisomers2010

    • Author(s)
      Kenji Mori
    • Journal Title

      Tetrahedron 66(in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RCAI-37, 56, 59, 60, 92, 101, and 102, cyclitol and carbasugar analogs of KRN7000: Their synthesis and bioactivity for mouse lymphocytes to produce Th1-biased cytokines2009

    • Author(s)
      Takuya Tashiro(7人中1番目)
    • Journal Title

      Bioorg. Med. Chem. 17

      Pages: 6360-6373

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] RCAI-37, 56, 59, 60, 92, 101, and 102, cyclitol and carbasugar analogs of KRN7000 : Their synthesis and bioactivity for mouse lymphocytes to produce Th1-biased cytokines2009

    • Author(s)
      Takuya Tashiro
    • Journal Title

      Bioorganic and Medicinal Chemistry 17

      Pages: 6360-6373

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] First synthesis and absolute configuration of a β-farnesene-trimethoxystyrene conjugate isolated from Pachypodanthium confine2009

    • Author(s)
      Masatsugu Koso
    • Journal Title

      Tetrahedron 65

      Pages: 9142-9145

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] First Synthesis of(±)-Basidifferquinone C, an Inducer for Fruiting-Body Formation in Polyporus arcularius2009

    • Author(s)
      Takashi Hashimoto
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry 73

      Pages: 2299-2302

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RCAI-61, the 6'-O-methylated analog of KRN7000: its synthesis and potent bioactivity for mouse lymphocytes to produce interferon-〓 in vivo2008

    • Author(s)
      Takuya Tashiro(7人中1番目)
    • Journal Title

      Tetrahedron Lett. 49

      Pages: 6827-6830

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] RCAI-17, 22, 24-26, 29, 31, 34-36, 38-40 and 88, the analogue of KRN7000 with a sulfonamide linkage: their synthesis and bioactivity for mouse natural killer T cells to produce Th2 biased cytokines2008

    • Author(s)
      Takuya Tashiro(8人中1番目)
    • Journal Title

      Bioorg. Med. Chem. 16

      Pages: 8896-8906

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] RCAI-61, the 6'-O-methylated analog of KRN7000: its synthesis and potent bioactivity for mouse lymphocytes to produce interferon-γ in vivo2008

    • Author(s)
      Takuya Tashiro
    • Journal Title

      Tetrahedron Lett. 49

      Pages: 6827-6830

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Identification of Attractive Volatiles in Aged Male Mouse Urine2008

    • Author(s)
      Kazumi Osada
    • Journal Title

      Chem. Senses 33

      Pages: 815-823

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RCAI-17, 22, 24-26, 29, 31, 34-36, 38-40 and 88, the analogue of KRN7000 with a sulfonamide linkage: their synthesis and bioactivity for mouse natural killer T cells to produce Th2 biased cytokines2008

    • Author(s)
      Takuya Tashiro
    • Journal Title

      Bioorg. Med. Chem. 16

      Pages: 8896-8906

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 2-Isopropyl-4,5-dihydrothiazole and 6-Hydroxy6-methyl-3-heptanone, the Pheromone Components of the Male Mouse, Mus musculus2008

    • Author(s)
      Takuya Tashiro
    • Journal Title

      Biosci. Biotechnol. Biochem. 72

      Pages: 2398-2402

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and absolute configuration of the male aggregation pheromone of the stink bug Erysareoris lewisi (Distant), (2Z,6R,1'S,5'S)-2-methyl-6-(4'-methylenebicyclo[3.1.0] hexyl)hept-2-en-1-ol2008

    • Author(s)
      Takuya Tashiro
    • Journal Title

      Tetrahedron:Asymmetry 19

      Pages: 1215-1223

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RCAI-8, 9, 18, 19, and 49-52, conformationally restricted analogues of KRN7000 with an azetidine or pyrrolidine ring: Their synthesis and bioactivity for mouse natural killer T cells to produce cytokines2008

    • Author(s)
      Ken-ichi Fuhshuku
    • Journal Title

      Bioorg. Med. Chem. 16

      Pages: 950-964

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Determination of the absolute configuration of the male aggregation pheromone, 2-methyl-6-(4'-methylenebicyclo[3.1.0]-hexyl)hept-2-en-1-ol, of the stink bug Erysarcoris lewisi (Distant) as 2Z,6R,1',5'S by its synthesis2008

    • Author(s)
      Kenji Mori
    • Journal Title

      Tetrahedron Lett. 49

      Pages: 354-357

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 免疫細胞に対してIFN-〓の産生を誘導する新規スフィンゴ糖脂質の開発2011

    • Author(s)
      田代卓哉
    • Organizer
      日本農芸化学会2010年度大会
    • Place of Presentation
      東京大学
    • Year and Date
      2011-03-28
    • Related Report
      2009 Final Research Report
  • [Presentation] 免疫細胞を活性化する新規糖脂質の合成研究2010

    • Author(s)
      田代卓哉
    • Organizer
      理研シンポジウム
    • Place of Presentation
      理化学研究所
    • Year and Date
      2010-01-29
    • Related Report
      2009 Final Research Report
  • [Presentation] 免疫細胞を活性化する新規糖脂質の合成研究2010

    • Author(s)
      田代卓哉
    • Organizer
      理研シンポジウム 第13回「生体分子の化学」
    • Place of Presentation
      理化学研究所(埼玉県)
    • Year and Date
      2010-01-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] 免疫細胞の一種であるナチュラルキラーt細胞を活性化する新規糖脂質の探索研究2009

    • Author(s)
      田代卓哉
    • Organizer
      第44回天然物談話会
    • Place of Presentation
      つくばグランドホテル
    • Year and Date
      2009-07-09
    • Related Report
      2009 Final Research Report
  • [Presentation] 免疫細胞の一種であるナチュラルキラーT細胞を活性化する新規糖脂質の探索研究2009

    • Author(s)
      田代卓哉
    • Organizer
      第44回天然物化学談話会
    • Place of Presentation
      つくばグランドホテル(茨城県)
    • Year and Date
      2009-07-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] マウス免疫細胞に対してIFN-〓の産生を誘導する新規スフィンゴ糖脂質類縁体の開発2009

    • Author(s)
      田代卓哉
    • Organizer
      日本農芸化学会2009年度大会
    • Place of Presentation
      福岡マリンメッセ
    • Year and Date
      2009-03-29
    • Related Report
      2009 Final Research Report
  • [Presentation] Newly synthesized glycolipids potentiate to produce large amount of IFN-〓 in vivo2009

    • Author(s)
      Takuya Tashiro
    • Organizer
      vivo、The 5th International Symposium on CD1/NKT Cells
    • Place of Presentation
      鎌倉プリンスホテル
    • Year and Date
      2009-03-24
    • Related Report
      2009 Final Research Report
  • [Presentation] ナチュラルキラー(NK)T細胞を活性化し、IFN-γの産生を強力に誘導する新規糖脂質RCAI-61の合成2008

    • Author(s)
      田代卓哉
    • Organizer
      第50回天然有機化合物討論会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2008-10-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] ナチュラルキラー(NK)T細胞を活性化し、IFN-〓の産生を強力に誘導する新規糖脂質RCAI-61の合成2008

    • Author(s)
      田代卓哉
    • Organizer
      第50回天然有機化合物討論会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2008-09-30
    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] 新規合成糖脂質およびその用途2010

    • Inventor(s)
      田代卓哉(5人中1番目)
    • Industrial Property Rights Holder
      理化学研究所
    • Filing Date
      2010-02-05
    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] 新規糖脂質及びその用途2008

    • Inventor(s)
      田代卓哉(6人中1番目)
    • Industrial Property Rights Holder
      理化学研究所
    • Filing Date
      2008-03-25
    • Related Report
      2009 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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