| Project/Area Number |
04557100
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Nagasaki University |
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Principal Investigator |
IRIE Hiroshi Faculty of Pharmaceutical Sciences, Nagasaki University Professor, 薬学部, 教授 (00025686)
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| Co-Investigator(Kenkyū-buntansha) |
TOKI Takashi Research Center, Daicel Chemical Industries, LTD,Reseach Director, 研究所, 研究員
MIYASHITA Masaaki Faculty of Science, Department of Chemistry, Professor, Hokkaido Univeresity, 理学部, 教授 (50006326)
HATAKEYAMA Susumi Pharmaceutical Sciences, Nagasaki University Associate Professor, 薬学部, 助教授 (20143000)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | spider toxin / polyamine / glutamic acid receptor / nervous toxin / nephilatoxins / histamine release / D-asparagine / ネフィラトキシン / 神経筋興奮伝達遮断 / ネフィラトキシン-8 / ネフィラトキシン類の全合成 / D-ネフィラトキシン-8 / D-ネフィラトキシン-12 / アジド中間体 / クモ毒素の全合成 / 神経筋興奮伝達遮断作用 / 含ポリアミンペプチド / アジド化合物 |
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| Research Abstract |
Nephilatoxins have been isolated from the venom of Joro spider (Nephila clavata) , which show the potent blocking activity to glutamic acid receptor in brain and induce histamine release from rat peritoneal mast call. We aimed at the total synthesis of the toxins and their congeners to make ample supply of their toxins possible. The feature of toxins are characterized by the structure consisting of an aromatic acid, some amino acids, and polyamines. Therefore, the key point of their synthesis depends upon how to construct polyamine moiety included in the toxin structures. We developed a useful method for the purpose using azide group in the place of amino group.
Based on the basic precise reseach work, we accomplished total synthesis of six toxins NPTX-7,8,9,10,11, and 12 and D-NPTX-8 and 12 having D-aspargine in the place of L-amino acid originaly present in genuin toxins in large quantity. Biological test of the samples thus synthesized provided instructive information about structure-activity relationship.
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