Synthetic Studies on Spider Toxins and Their Congeners and Their Biological Activities

蜘蛛毒素及其同源物的合成及其生物活性研究

• 批准号: 04557100
• 负责人: IRIE Hiroshi
• 金额: $ 2.18万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557100/
• 关键词: 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

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.

已从乔罗蜘蛛 (Nephila clavata) 的毒液中分离出 Nephilatoxins，该毒素对大脑中的谷氨酸受体表现出有效的阻断活性，并诱导大鼠腹膜肥大释放组胺。我们的目标是毒素及其同源物的全合成，以使其毒素的充足供应成为可能。毒素的特征是其结构由芳香酸、部分氨基酸、多胺组成。因此，它们的合成关键在于如何构建毒素结构中包含的多胺部分。我们开发了一种有用的方法，用叠氮基代替氨基。在基础精密研究工作的基础上，我们完成了六种毒素NPTX-7、8、9、10、11和12以及D-的全合成。 NPTX-8和12用D-天冬酰胺代替原来大量存在于Genuin毒素中的L-氨基酸。由此合成的样品的生物学测试提供了关于结构-活性关系的指导性信息。

项目成果

M. Miyashita et al.: "Total Synthesis of Nephilatoxin-7,a New Neurotoxins of Joro Spider ( Nephila clavata)" J. Chem. Soc. , Chem. Commun.1995( submitted). (1995)

M. Miyashita 等人：“Joro 蜘蛛（Nephila clavata）的新神经毒素 Nephilatoxin-7 的全合成”J. Chem。

M. Miyashita et al.: "Synthetic studies on Spider Neurotoxins (II):Total Synthesis of Nephilatoxins ( NPTX-10 and NPTX-12) , New Neurotoxins of Joro Spider ( Nephila clavata)" Tetrahedron Letters. 33. 2837-2840 (1992)

M. Miyashita 等人：“蜘蛛神经毒素的合成研究 (II)：蜘蛛毒素（NPTX-10 和 NPTX-12）的全合成，Joro 蜘蛛（Nephila clavata）的新神经毒素”四面体快报。

Masaaki Miyashita: "Synthetic Studies on Spider Neurotoxins(I):Total Synthesis of Nephilatoxins(NPTX-9 and NPTX-11),New Neurotoxins of Joro Spider(Nephila clavata)" Tetrahedron Letters. 33. 2833-2836 (1992)

Masaaki Miyashita：“蜘蛛神经毒素的合成研究（I）：蜘蛛毒素（NPTX-9和NPTX-11）的全合成，Joro蜘蛛（Nephila clavata）的新神经毒素”四面体快报。

M.Miyashita, H.Sato, M.Matsushita, Y.Kusumegi, T.Toki, A.Yoshikoshi, T.Yanami, Y.Kikuchi, C.Takasaki, T.Nakajima, and H.Irie: "Synthetic Studies on Spider Neurotoxins (II) : Total Synthesis of Nephilatoxins (NPTX-10 and NPTX-12) , New Neurotoxins of joro

M.Miyashita、H.Sato、M.Matsushita、Y.Kusumegi、T.Toki、A.Yoshikoshi、T.Yanami、Y.Kikuchi、C.Takasaki、T.Nakajima 和 H.Irie：“蜘蛛的综合研究”

M.Miyashita, H.Sato, A.Yoshikoshi, T.Toki, M.Matsuhita, H.Irie, T.Yanami, Y.Kikuchi, C.Takasaki, and T.Nakajima: "synthetic Studies on Spider Neurotoxins (1) : Total Synthesis of Nephilatoxins (NPTX-9 and NPTX-11) , New Neurotoxins of Joro Spider (Nephila

M.Miyashita、H.Sato、A.Yoshikoshi、T.Toki、M.Matsuhita、H.Irie、T.Yanami、Y.Kikuchi、C.Takasaki 和 T.Nakajima：“蜘蛛神经毒素的合成研究 (1)