Synthesis of glutamine transporter inhibitors regulating amino acids concentrations in neurotransmission system

• Project/Area Number: 19510228
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: Suntory Institute for Bioorganic Research
• Principal Investigator: SHIMAMOTO Keiko Suntory Institute for Bioorganic Research, 研究員 (70235638)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: グルタミン / トランスポーター / 阻害剤 / グリア細胞 / 立体配座固定 / グルタミン酸 / 中性アミノ酸 / シスチン / ヘテロエクスチェンジ

Research Abstract

Extracellular concentrations of amino acids and sugars are regulated by transporters. In order to elucidate physiological roles in neurotransmission system and substrate recognition mechanisms of these transporters, we synthesized selective inhibitors for neutral amino acid transporter (ASCT2) and glutamate-cyctine exchanger (xCT).

Research Products

• [Journal Article] Improved synthesis and in vitro/in vivo activities of natural product-inspired, artificial glutamate analogs (2010)
  • Author(s): M. Oikawa, M. Ikoma, M. Sasaki, M.B. Gill, G.T. Swanson, K. Shimamoto, R. Sakai
  • Journal Title: Bioorg. Med. Chem. 10 Pages: 3795-3804
  • NAID: 120002169301
  • Peer Reviewed
• [Journal Article] Regioselective Domino Metathesis of Unsymmetrical 7-Oxanorbornenes with Electron-rich Vinyl Acetate toward Biologically Active Glutamate Analogues (2009)
  • Author(s): M. Oikawa, M. Ikoma, M. Sasaki, M.B. Gill, G.T. Swanson, K. Shimamoto, R. Sakai
  • Journal Title: Eur. J. Org. Chem. 32 Pages: 5531-5548
  • Peer Reviewed
• [Journal Article] Regioselective Domino Metathesis of Unsymmetrical 7-Oxanorbornenes with Electron-rich Vinyl Acetate toward Biologically Active Glutamate Analogues (2009)
  • Author(s): M.Oikawa
  • Journal Title: Eur.J.Org.Chem. 32 Pages: 5531-5548
  • Peer Reviewed
• [Journal Article] Glutamate transporter blockers for elucidation of the function of excitatory neurotransmission systems. (2008)
  • Author(s): K. Shimamoto
  • Journal Title: Chem. Rec. 8 Pages: 182-199
  • Peer Reviewed
• [Journal Article] Regioselective Domino Metathesis of 7-Oxanorbornenes and Its Application to the Synthesis of Biologically Active Glutamate Analogues (2008)
  • Author(s): M. Ikoma, M. Oikawa, M.B. Gill, G.T. Swanson, R. Sakai, K. Shimamoto, M. Sasaki
  • Journal Title: Eur. J. Org. Chem. 31 Pages: 5215-5220
  • Peer Reviewed
• [Journal Article] Low-affinity excitatory amino acid uptake in hippocampal astrocytes: a possible role of Na+/dicarboxylate cotransporters (2008)
  • Author(s): A.T. Holten, N.C. Danbolt, K. Shimamoto, V. Gundersen
  • Journal Title: Glia 58 Pages: 990-997
  • Peer Reviewed
• [Journal Article] Rapid and efficient synthesis of dysiherbaine and analogues to explore structure-activity relationships (2008)
  • Author(s): M. Sasaki, K. Tsubone, K. Aoki, N. Akiyama, M. Shoji, M. Oikawa, R. Sakai, K. Shimamoto
  • Journal Title: J. Org. Chem. 73 Pages: 264-273
  • Peer Reviewed
• [Journal Article] Low-affinity excitatory amino acid uptake in hipocampal astrocytes : A possible role of Na+/dicarboxylate cotransporters (2008)
  • Author(s): A. T. Holten
  • Journal Title: Glia 56 Pages: 990-997
  • Peer Reviewed
• [Journal Article] Regioselective Domino Metathesis of 7-Oxanorbornenes and its Application tothe Synthesis of Biologically Active glutamate Analogues (2008)
  • Author(s): M. Ikoma
  • Journal Title: Eur. J. Org. Chem 2008 Pages: 5215-20
  • Peer Reviewed
• [Journal Article] Rapid and efficient synthesis of dysiherbaine and analogues to explore structure-activity relationships (2008)
  • Author(s): M. Sasaki
  • Journal Title: Journal of Organic Chemistry 73 Pages: 264-273
  • Peer Reviewed
• [Journal Article] Glutamate transporter GLAST/EAAT1 directs cell surface expression of FXYD2/gamma subunit of Na, K-ATPase in human fetal astrocytes (2007)
  • Author(s): M. Gegelashvili, A. Rodriguez-Kern, L. Sung, K. Shimamoto, G. Gegelashvili
  • Journal Title: Neurochem. Int. 50 Pages: 916-920
• [Journal Article] Glutamate transporter GLAST/EAATl directs cell surface expression of FXYD2/gamma subunit of Na,K-ATPase in human fetal astrocytes (2007)
  • Author(s): M. Gegelashvili
  • Journal Title: Neurochemistry International 50 Pages: 916-920
  • Peer Reviewed
• [Journal Article] 毒を作って何になる……?!-神経伝達機構の解明で活躍する化合物TBOA (2007)
  • Author(s): 島本 啓子
  • Journal Title: 化学 62 Pages: 39-42
  • Peer Reviewed