Chemical Syntheses of Natural and Designed Molecules : Innovative Research on Their New Functions, Antibodies and Receptors

天然分子和设计分子的化学合成：对其新功能、抗体和受体的创新研究

• 批准号: 19001003
• 负责人: HIRAMA Masahirohi
• 金额: $ 272.06万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Specially Promoted Research
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19001003/
• 关键词: 全合成; シガトキシン; モノクローナル抗体; ELISA; チャネル; エンジイン; C1027; クロモフォア; Naチャネル; チャネル結合部位; シガテラ; 抗体; イムノアッセイ; エンジイン抗生物質; ナトリウムチャネル; シガトキシンCTX1B; 抗シガトキシン抗体; ハプテン; ヒト型抗体; ELISAキット; ケダルシジン; マデュロペプチン; C-1027クロモフォア; サマリウムアイオダイド; カリブ海産シガトキシンC-CTX; 51

We have developed a general method for the total syntheses of ciguatoxins. Practical total synthesis of ciguatoxins allowed us to use them for interdisciplinary researches, such as unveiling the gating mechanism of voltage sensitive sodium channels. Highly sensitive anti-CTXlB monoclonal antibodiy and immunoassay method were developed to detect major congeners of ciguatoxin. Some of the previously prepared antibodies were modified for treating the human ciguatera poisoning. Furthermore, designed pseudo-ciguatoxins were also synthesized as bio-probes for understanding the biological mechanisms. On the other hand, total syntheses of the extremely potent antitumor chromoprotein nine-membered enediyne antibiotics and cortistatins were accomplished.

我们开发了一种通用的雪卡毒素全合成方法。雪卡毒素的实际全合成使我们能够将其用于跨学科研究，例如揭示电压敏感钠通道的门控机制。建立了检测雪卡毒素主要同系物的高灵敏度抗CTX1B单抗和免疫分析方法。之前制备的一些抗体被修饰，用于治疗人类雪卡毒素。此外，还合成了设计的假雪卡毒素作为生物探针，以了解其生物学机制。另一方面，完成了极强的抗肿瘤显色蛋白九元烯二炔类抗生素和皮质酮的全合成。

项目成果

First Toxin Profile of Ciguateric Fish in Madeira Arquipelago (Europe)

• DOI: 10.1021/ac100516q
• 发表时间: 2010-07-15
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Otero, Paz;Perez, Sheila;Botana, Luis M.
• 通讯作者: Botana, Luis M.

天然物の全合成2000-2008(日本)

天然产物全合成2000-2008（日本）

• 发表时间: 2009
• 作者: 横島聡(;他2名)
• 通讯作者: 他2名)

How protein recognizes ladder-like polycyclic ethers : interactions between ciguatoxin (CTX3C) fragments and its specific antibody 10C9

蛋白质如何识别梯状多环醚：雪卡毒素 (CTX3C) 片段与其特异性抗体 10C9 之间的相互作用

• 发表时间: 2008
• 期刊: Journal of Biological Chemistry 283
• 作者: Mihoko Ui;Yoshikazu Tanaka;Takeshi Tsumuraya;Ikuo Fujii;Masayuki Inoue;Masahiro Hirama;Kouhei Tsumoto
• 通讯作者: Kouhei Tsumoto

Efficient and stereoselective installation of isoquinoline: formal total synthesis of cortistatin A

• DOI: 10.1016/j.tetlet.2009.02.038
• 发表时间: 2009-07
• 期刊: Tetrahedron Letters
• 影响因子: 1.8
• 作者: Shuji Yamashita;Kazuki Kitajima;K. Iso;M. Hirama*

A concise route to the C2-symmetric tricyclic skeleton of ryanodine

• DOI: 10.1016/j.tetlet.2008.12.054
• 发表时间: 2009-03-04
• 期刊: TETRAHEDRON LETTERS
• 影响因子: 1.8
• 作者: Hagiwara, Koji;Himuro, Masafumi;Inoue, Masayuki
• 通讯作者: Inoue, Masayuki