2006 Fiscal Year Final Research Report Summary
Total Synthesis of Ciguatoxins and Studies on The Antibodies and The Mechanism of Action
| Project/Area Number |
14103019
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Bioorganic chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
HIRAMA Masahiro Tohoku University, Graduate School of Science, Professor, 大学院理学研究科, 教授 (30165203)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Masayuki Tohoku University, Graduate School of Science, Associate Professor, 大学院理学研究科, 助教授 (70322998)
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| Project Period (FY) |
2002 – 2006
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| Keywords | Ciguatoxin / Polyether / Ciguatera Poisoning / Total Synthesis / Immunoassay / Antibody / Neutralization of Toxicity / Sodium Channel |
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| Research Abstract |
Ciguatera poisoning is an important medical issue in the tropical and subtropical regions. The first total synthesis of ciguatoxin CTX3C, one of the causative toxins, through "unified convergent strategy, i.e., [X+2+Y] polyether assembly" was accomplished in 2001.
1.We then have developed the practical second-generation total synthesis of CTX3C.
2.Moreover, we have successfully applied it to synthesize 51-HydroxyCTX3C and CTX1B. Further methodological improvements allowed us to prepare a few mg of CTX3C and 51-HydroxyCTX3C, respectively, which be used for interdisciplinary researches.
3.Highly sensitive monoclonal antibody 8H2 was developed against CTX1B, 51-HydroxyCTX3C, and so on.
4.Sandwich Immunoassay using mAbs 8H2 and 10C9 was able to detect 51-HydroxyCTX at the level of pg/ml.
5.Sandwich immunoassay using mAbs 10C9 and 3D11 detected CTX3C in ciguateric fish caught in the Okinawa sea area.
6.Mice poisoned with CTX3C were cured by monoclonal antibodies we developed, which will be applied for humans. In addition, vaccines for ciguatera poisoning would be developed.
7.The central 9-membered F ring of ciguatoxins is proved to be crucial for their toxicity.
8.Synthetic ciguatoxins and bio-probes such as the conjugates with biotin will unveil the VSSC-ligand interaction at the atomic lebel and the gating mechanism.
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Research Products
(111 results)
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[Journal Article] 海洋天然物の全合成2003
Author(s)
平間 正博
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Journal Title
海洋天然物化学-化合物ライブラリーとしての評価(21世紀の化学の潮流を探る報告書No.16)(日本化学会)
Pages: 21-26
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Characterization of 11-Dehydro-Thromboxane B_2 Recombinant Antibody Obtained by Phage Display Technology.2003
Author(s)
L.-R.Thuruta, Y.Tomioka, T.Hishinuma, Y.Kato, K.Itoh, T.Suzuki, H.Oguri, M.Hirama, J.Goto, M.Mizugaki
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Journal Title
Prostaglandins, Leukotrienes and Essential Fatty Acids 68
Pages: 273-284
Description
「研究成果報告書概要(欧文)」より
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