2019 Fiscal Year Research-status Report
Application of gold-catalyzed glycosylation under aqueous condition for the tumor-localized in vivo synthesis of anticancer drugs
| Project/Area Number |
19K15708
|
|---|
| Research Institution | Institute of Physical and Chemical Research |
|---|
Principal Investigator |
張 宗哲 国立研究開発法人理化学研究所, 開拓研究本部, 特別研究員 (00774853)
|
|---|
| Project Period (FY) |
2019-04-01 – 2021-03-31
|
| Keywords | gold catalysis / chemical glycosylation / drug-release / biocompatibility / metal-carrier |
|---|
| Outline of Annual Research Achievements |
To develop an anticancer therapy based on a novel gold-catalyzed chemical glycosylation under aqueous condition. Two areas are being investigated.
1. The dozens of new functional groups were synthesized and used as leaving groups in anomeric center of glycan. Those leaving groups in glycan by gold-catalyzed activation under water were confirmed. A new glycosyl donor by using the optimal leaving group was found for using in the project.
2. Gold complex was loaded on albumin as a gold-carrier protein. The gold-carrier protein was proven that it activated the new glycosyl donor without deactivation of gold catalyst. To confer cancer-targeting character on the system, N-glycan is being loading onto the gold-carrier protein.
|
| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
A whole new leaving group for gold-mediated chemical glycosylation was established in the progress. The efficiency of gold-catalyzed glycosylation depended on the structure and electronic effect of leaving group in glycan. After systematic investigation, the optimal leaving group in glycan can be mediated under aqueous solution not only by a gold-complex catalysis but also by a gold-carrier protein. In contrast, most of chemical glycosylation examples only can be mediated by Lewis acid in anhydrous organic solvent since water can quench Lewis acid. The significant progress overcame difficulty of the project, namely, how to use Lewis acid to activate leaving group in glycan under water.
|
| Strategy for Future Research Activity |
Utilizing intramolecular aglycon delivery strategy to link the new glycosyl donor with a drug precursor will be able to finish the prodrug. Next stage will focus on in vitro studies of drug release via activation of the prodrug by cancer-targeting and gold-carrier albumin. Different kinds of cancer cell lines will be used in the vitro studies to confirm cell cytotoxicity assay. Using this work, the awardee will then apply it for in vivo drug release in mice experiment.
|
Research Products
(6 results)
