SEARCH FOR GLUTAMATE AGONISTS AND ANTAGONINSTS FROM BASIDOMYCETES

• Project/Area Number: 05671739
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: TOHOKU UNIVERSITY
• Principal Investigator: FUSHIYA Shinji TOHOKU UNIVERSITY PHARMACEUTICAL INSTITUTE ASSOCIATE PROFESSOR, 薬学部, 助教授 (80108563)
• Project Period (FY): 1993 – 1994
• Project Status: Completed (Fiscal Year 1994)
• Budget Amount: ¥2,100,000 (Direct Cost: ¥2,100,000); Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000); Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: Basidiomycetes / Amanita pantherina / Clitocybe acromelalga / glutamate receptors / NMDA receptor / neuroexciting activity / acidic amino acids / opines / 有毒担子菌 / アクロメリン酸 / アミノ酸 / 興奮性神経伝達物質 / グルタミン酸アゴニスト / グルタミン酸アンタゴニスト

Research Abstract

Neurologically active amino acid derivatives were isolated from toxic mushrooms, Amanita panthrina and Clitocybe acromelalga.
1) Two amino acids showing an antagonistic activity toward NMDA receptor subtype were isolated from A.pantherina and determined to be (2R,1'R) -and (2R,1'S) -2-amino-3 (1,2-dicarboxy ethyl-thio) propanoic acids (ADPA). Four stereoisomers of ADPA were synthesized from fumaric acid and L- (or D-) cysteine to evaluate for the activity on NMDA receptor. They showed almost the same magnitude of activity.
2) Acromelic acids D and E,analogs of potent agonists of glutamic acid, were isolated from C.acromelalga. L-Stizolobic acid and L-stizolobinic acid, biosynthetic precursors of acromelic acids and antagonists of quisqualic receptor, were isolated from C.acromelalga. beta-Cyano-L-alanine and its gamma-glutamylpeptide, the neurolathyrogens of Vicia plants, were also isolated. The characteristic syndromes caused by ingestion of this mushroom might be attributed to these neurologically active constituents.
Three amino acids, valinopine, epi-leucinopine and isoleucinopine belonging to the opine family were also isolated from C.acromelalga.

Research Products

• [Publications] Shinji Fushiya: "(2R),(1'R) and (2R),(1'S)-2-Amino-3(1,2-Dicarboxyethylthio)propanoic Acids,NMDA Antagonists from Amanita Pantherina" Chemical and Pharmaceutical Bulletin. 41. 484-486 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shinji Fushiya: "β-Cyano-L-Alanine and γ-Glutamyl-β-Cyano-L-Alanine,the Neurolathyrogens from a Toxic Mushroom,Clitocybe Acromelalga" Phytochemistry. 33. 53-55 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shinji Fushiya: "Three New Amino Acids from a Poisonous Mushroom,Clitocybe Acromelalga" Tetrahedron Letters. 35. 8201-8204 (1994)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] S.Fushiya, Q.-Q.Gu, K.Ishikawa, S.Fnayama and S.Nozoe: "(2R), (1'R) and (2R), (1'S) -2-Amino-3- (1,2-dicarboxyethylthylthio) propanoic acids, NMDA antagonists from Amanita pantherina" Chem.Pharm.Bull.41. 484 (1993)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] S.Fushiya, S.Sato, G.Kusano and S.Nozoe: "beta-Cyano-L-alanine and gamma-glutamyl-beta-cyano-L-alanine, the neurolathyrogens from a toxic mushroom, Clitocybe acromelalga" Phytochemistry. 33. 53 (1993)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] S.Fushiya, S.Yamada, M.Matsuda and S.Nozoe: "Three new amino acids from a poisonous mushroom, Clitocybe acromelalga" Tetrahedron Lett.35. 8201 (1994)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shinji Fushiya: "(2R),(I′R)and(2R),(I′R)-2-Amino-3(1、2-Dicarboxyethylthio)propanoic Acids,NMDA Antagonists from Amanita Pantherina" Chemistry and Pharmaceutical Bulletin. 41. 484-486 (1993)
• [Publications] Shinji Fushiya: "β-Cyano-L-Alanine and γ-Glutamyul-β-Cyano-L-Alanine,the Neurolathyrogens from a Toxic Mushroom,Clitocybe Acromelalga" Phytochemistry. 33. 53-55 (1993)
• [Publications] Shinji Fushiya: "Fhree New Amino Acids from a Poisonous Mushroom,Clitocybe Acromelalga21GC01:Tetrahedron Letters" 35. 8201-8204 (1994)
• [Publications] Shinji Fushiya: "(2R),(1'R)and(2R),(1'S)-2-Amino-3-(1,2-Dicarboxyethylthio)propanoic Acids,NMDA Antagonists from Amanita Pantherina" Chem.Pharm.Bull.41. 484-486 (1993)
• [Publications] Shinji Fushiya: "β-Cyano-L-Alanine and γ-Glutamyl-β-Cyano-L-Alanine,the Neurolathyrogens from a Toxic Mushroom,Cltocybe Acromelalga" Phyto chemistry. 33. 53-55 (1993)