A Study on Designed Hapten Aimed at Anti-ciguatoxin Monoclonal Antibody

抗雪卡毒素单克隆抗体半抗原设计的研究

• 批准号: 10558096
• 负责人: HIRAMA Masahiro
• 金额: $ 8万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10558096/
• 关键词: ciguatoxin; antibody; hapten; antigen; gene; synthesis; olefin metathesis; ELISA; モノクローナル抗体; 人工抗原; シガテラ; 抗シガトキシン抗体; 海産ポリエーテル; コンジュゲート; 免疫

The ABC-ring fragment of ciguatoxin was synthesized as a C2 epimeric mixture (1 : 1 ). The mixture, which was designed as a possible hapten for preparing an anti-ciguatoxin monoclonal antibody, was conjugated with a carrier protein (KLH) and then used for immunization of mice. The three monoclonal antibodies (mAbs) obtained have shown an appreciable reactivity to the hapten. Each mAb discriminated configuration of the C2 hydroxy group of the ABC-ring fragment. The mAb which showed reactivity to the 2S-fragment was cross-reacted with ciguatoxin. Furthermore, new and efficient synthetic methods utilizing olefin methathesis were developed and several designed haptens have been prepared and conjugated with KLH and BSA, which have been used for immunization of mice.

雪卡毒素的ABC环片段被合成为C2差向异构体混合物(1:1)。该混合物被设计为可能的半抗原，用于制备抗雪卡毒素单克隆抗体，与载体蛋白（KLH）缀合，然后用于小鼠的免疫。获得的三种单克隆抗体 (mAb) 对半抗原表现出明显的反应性。每种 mAb 都能区分 ABC 环片段的 C2 羟基的构型。对 2S 片段表现出反应性的 mAb 与雪卡毒素发生交叉反应。此外，还开发了利用烯烃复分解的新的有效合成方法，并制备了几种设计的半抗原并与KLH和BSA缀合，这些半抗原已用于小鼠的免疫。

项目成果

Hiroki Oguri et al.: "Designed Hapten Aimed at Anti-ciguatoxin Antibody:Synthesis,Immunization and Discrimination of the C2 Configuration" SYNTHESIS. (発表予定). (1999)

Hiroki Oguri 等人：“针对抗雪卡毒素抗体设计的半抗原：C2 配置的合成、免疫和区分”综合（待提交）。

Y.Naguo, H.Oguri, Y.Shindo, S.Sasaki, T.Oishi, M.Hirama. Y.Tomioka, M.Mizugaki, and T.Tsumuraya: "A Surface Plasmon Resonance Study of the Monoclonal Antibodies Bindng to the Synthetic ABC-ring Fragments of Ciguatoxins."(submitted for publication.).

Y.Naguo，H.Oguri，Y.Shindo，S.Sasaki，T.Oishi，M.Hirama。

H.Oguri,S.Sasaki,T.Oishi,and M.Hirama,: "Expeditious Tandem-Metathesis Route to the AB-ring Fragment of Ciguatoxin."Tetrahedron Lett.,. 40. 5405-5408 (1999)

H.Oguri、S.Sasaki、T.Oishi 和 M.Hirama，“雪卡毒素 AB 环片段的快速串联复分解路线”。

T.Oishi: "Convergent Synthesis of the IJKLM Ring Fragment of Ciguatoxin CTX3C"Chem. Commun.. 2035-2036 (1999)

T.Oishi：“雪卡毒素 CTX3C 的 IJKLM 环片段的聚合合成”Chem。

H.Oguri,S.Sasaki,S.Hishiyama,T.Oishi,M.Hirama,T.Tumuraya,Y.Tomioka,and M.Mizugaki,: "Designed Hapten Aimed at Anti-ciguatoxin Monocronal Antibody : Synthesis, Immunization and Descrimination of the C2 Configuration."Synthesis, Special Issue,. 1431-1436 (1

H.Oguri、S.Sasaki、S.Hishiyama、T.Oishi、M.Hirama、T.Tumuraya、Y.Tomioka 和 M.Mizugaki，：“针对抗雪卡毒素单克隆抗体设计的半抗原：合成、免疫和鉴别