2014 Fiscal Year Research-status Report
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
| Project/Area Number |
24710242
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
ファイナ ガルシア・マーティン 北海道大学, 先端生命科学研究科(研究院), 助教 (30537080)
|
|---|
| Project Period (FY) |
2012-04-01 – 2016-03-31
|
| Keywords | Glycoconjugates / β-glucan / Solid-phase synthesis / Binding Assay |
|---|
| Outline of Annual Research Achievements |
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.
|
| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
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.
|
| Strategy for Future Research Activity |
- 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)
|
| Causes of Carryover |
Further, as principal investigator got pregnant, she could not do chemical experiments so next year she will perform all those experiments.
|
| Expenditure Plan for Carryover Budget |
Payment of chemical and biological reagents. Payment of material and research facility. Payment of sending compounds to collaborators. Payment for conferences to present our results
|
-
-
[Journal Article] Delineating binding modes of Gal/GalNAc and structural elements of the molecular recognition of tumor-associated mucin glycopeptides by the human macrophage galactose-type lectin2014
Author(s)
Filipa Marcelo, Fayna Garcia-Martin, Takahiko Matsushita, Joao Sardinha, Helena Coelho, Anneloes Oude-Vrielink, Christiane Koller, Sabine Andre, Eurico J Cabrita, Hans-Joachim Gabius, Shin-ichiro Nishimura, Jesus Jimenez-Barbero, and F Javier Canada
-
Journal Title
Chemistry, an European Journal
Volume: 20
Pages: 16147-16155
DOI
Peer Reviewed / Acknowledgement Compliant
