2020 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
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| Research Institution | Institute of Physical and Chemical Research |
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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)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | gold catalysis / artificial metalloenzyme / drug-release / metal-carrier / biocompatibility |
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| Outline of Annual Research Achievements |
To achieve an anticancer therapy in vivo based on a gold-catalyzed chemical glycosylation, a gold artificial metalloenzyme (ArM) was developed as a trigger for activation the gold-catalyzed chemical glycosylation. Moreover, the gold ArM also can catalyze the conversion of a prodrug into a anticancer drug for application in cancer therapy. The strategy is based on the gold-catalyzed activation of a phenanthridinium-based prodrug via hydroamination under physiological conditions. To make the prodrug strategy biocompatible, the gold ArM, rather than the free gold metal, was used a trigger for activation of the prodrug. The albumin-based gold ArM protected the catalytic activity of the bound gold metal even in the presence of up to 1 mM glutathione in vitro. The drug synthesized via the gold ArM exerted a therapeutic effect in cell-based assays, highlighting the potential usefulness of the gold ArM in anticancer applications.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
In last year, the awardee has found a whole new leaving group that can be incorporated into glycan for gold-mediated chemical glycosylation on protein under physiological condition. To carry out the tumor-localized in vivo synthesis of anticancer drugs via chemical glycosylation, a tumor-targeting glycosylated gold artificial meatlloenzyme is a necessary trigger for the issue. In this year, the awardee succeeded to develop the gold artificial metalloenzyme (ArM) and demonstrated that the gold ArM can activate the whole new leaving group under physiological condition in good turnover number. The significant progress is a key step to achieve the goal of the study because gold ArM can be modified to a glycosylated gold ArM to promote in vivo chemical glycosylation on targeted tumor future.
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| Strategy for Future Research Activity |
Next stage will focus on in vitro studies of drug synthesis via in vivo chemical glycosylation by the cancer-targeting the glycosylated gold ArM. 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.
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| Causes of Carryover |
Because of the novel corona virus disease (COVID-19). the research was stopped for few months so that the budget did not used so much. In next year, the awardee plan to buy more cancer cells for the research.
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