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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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | biocatalysis / biocompatibility / artificial metalloenzyme / gold catalysis / drug synthesis / Artificial metalloenzyme / Gold-mediated reaction / Glycan / Prodrug / drug-release / metal-carrier / chemical glycosylation / Gold-catalysis / Prodrug activation / Chemical glycosylation / Glycoalbumin DDS |
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| Outline of Research at the Start |
Due to the adverse health effects caused by anticancer drug side effects, chemotherapy can be a laborious and often painful process for patients. The aim of this proposal is to develop a gold catalyzed chemical glycosylation to synthesize glycoconjugates as anticancer drugs. Together with cancer-targeting glycoalbumin DDS (drug delivery system), this approach can locally synthesize cytotoxic drugs within tumor tissues, while minimizing unnecessary drug interactions with normal, healthy tissues; thereby reducing unwanted drug side effects.
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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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| 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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Report
(4 results)
Research Products
(18 results)
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[Journal Article] In vivo metal-catalyzed SeCT therapy by a proapoptotic peptide.2021
Author(s)
hmad, P.; Muguruma, K.; Chang, T.-C.; Tamura, S.; Tsubokura, K.; Egawa, Y.; Suzuki, T.; Dohmae, N.; Nakao, Y.; *Tanaka, K.
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Journal Title
Chem. Sci.
Volume: 12
Issue: 37
Pages: 12266-12273
DOI
Related Report
Peer Reviewed / Open Access
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