2019 Fiscal Year Final Research Report
Application of gold-catalyzed 2-ethynylbenzamide cyclization for the tumor-localized in vivo release of anticancer drugs
| Project/Area Number |
18K14347
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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 |
Vong Kenward 国立研究開発法人理化学研究所, 開拓研究本部, 基礎科学特別研究員 (50775369)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Keywords | biocompatibility / artificial metalloenzyme / enzymes / gold catalysis / drug release |
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| Outline of Final Research Achievements |
In this project, we pursued two aspects related to biocatalysis. First, we focused on the development of albumin-based artificial metalloenzymes (ArM). We revealed that these systems were highly biocompatible due to their prevention of glutathione entry into the hydrophobic binding pocket of albumin. Using this technology, we developed a prodrug system that used ring-closing metathesis to synthesize umbelliprenin in cell cultures. In addition, we also adapted this system to design and develop an ethylene sensing probe. This probe was then used for the spatiotemporal detection of ethylene biosynthesis in fruits and leaves. Another aspect of biocatalysis that we explored was the development of an Au(I)-mediated ethynylbenzamide cyclization reaction. This reaction could be adapted to release amine containing drugs like doxorubicin and endoxifen. The activation of these prodrugs was shown to proceed effectively in various cell-based assays.
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| Free Research Field |
Biocatalysis
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| Academic Significance and Societal Importance of the Research Achievements |
This is basic research done to develop new systems and reactions that can potentially be used to create new targeted drug therapies in the future. The research results were disseminated to the scientific community through refereed publications, as well as conferences.
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