2021 Fiscal Year Final Research 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 Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Chang Tsung-Che 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 | biocatalysis / biocompatibility / artificial metalloenzyme / gold catalysis / drug synthesis |
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| Outline of Final Research Achievements |
Chemotherapy is one of the many strategies for treating cancer. However, many chemotherapy drugs produce unwanted side effects because in addition to attacking cancer cells, they cause collateral damage to healthy cells. One strategy for minimizing side effects is to use a prodrug―an inactive compound that is converted into an active drug on undergoing a chemical reaction at the target site. The project introduce a strategy based on the gold-catalyzed a phenanthridinium-based prodrug via hydroamination in aqueous condition. To make the strategy biocompatible, a gold artificial metalloenzyme (ArM) based on human serum albumin, rather than the free gold catalyst, was used for prodrug activation. The albumin-based gold ArM protected the catalytic activity of the bound gold metal even in the presence of up to 1 mM glutathione. The drug synthesized via the gold ArM exerted a therapeutic effect in cell-based assays, highlighting the potential usefulness of the gold ArM in vivo applications
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| Free Research Field |
Chemical Biology
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| Academic Significance and Societal Importance of the Research Achievements |
This is fundamental research that aims to produce new systems and reactions that could one day be exploited to develop new targeted medicinal therapies. The findings of the study were distributed to the scientific community through peer-reviewed journals and conferences.
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