| 研究実績の概要 |
βーグルカン構造に基づく新規ワクチンアジュバントの開発
The objective of the research project is the obtaining of glycoconjugates compounds with potential application in immunotherapy. Among others glycoconjugates, we focus on 1,3-β-glucan and further biological studies. The hypothesis is that 1,3-β-glucan as ligands of Dectin-1 can stimulate the immune system and the feasibility to be used as adjuvants.
During FY2014, we focus on getting short length saccharides and we obtained 4, 5 and 6 mer 1,3-β-glucan. Optimization of solid-phase method was performed and still ongoing for branched 1,6-β-glucan.
Even if in the modeling and docking experiments it was seen that in the binding site no more than four or five saccharides could be placed, by STD-NMR studies, the 6mer 1,3-β-glucan could not bind to Dectin-1. Thus, biological effect might be due to structural and/or valency reasons. Taking into account those observations, we have decided to synthesize multiple antigenic peptide presenting several 1,3-β-glucan in one compound. The synthesis was performed successfully and the purification step is the bottleneck of this procedure but likely soon we could get some successful results.
Further, a new binding assay based on microarray technique was optimized and ready to be used with our hit compounds.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
3: やや遅れている
理由
As principal investigator got pregnant, she was not allowed to perform any chemical reaction so those procedures were partially stopped.
The researcher will keep synthesizing 1,3-and 1,6 β-glucan candidates as Dectin-1 ligands. Once the library is obtained, compounds will be evaluated by just optimized novel microarray assay. As single compound could not bind to Dectin-1, we hypothesize that multivalency may influence the binding.
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| 今後の研究の推進方策 |
- Continue the synthesis of linear and branched 1,3-1,6-β-glucan.
- Multivalency 1,3-β-glucan
- Novel Glycanarray assay with Dectin-1-Fc fusion protein
- Dectin-1 binding of hit candidates will be also evaluated by STD NMR in collaboration with Prof. Jimenez-Barbero (CSIC, Spain).
- Best candidates will be evaluated at group of Prof. Claude Leclerc at Institute Pasteur (Paris)
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