2019 Fiscal Year Annual 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 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-catalyzed reaction / drug release |
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| Outline of Annual Research Achievements |
1) Development of gold-catalyzed, drug release reactions: An Au(I)-mediated ethynylbenzamide cyclization reaction was developed for the release of amine containing drugs like doxorubicin and endoxifen. The activation of these prodrugs was shown to proceed effectively in various cell-based assays. Of significant note, drug release was shown to be orthogonally activated by gold without interference from other transition metals (i.e. palladium and ruthenium). This paper has been finalized and is in the process of peer review/revision.
2) Development of artificial metalloenzymes: An albumin-based artificial metalloenzyme (ArM) was developed for the activation of prodrugs via ring-closing metathesis. Mechanistic studies revealed that biocompatibility is mainly conferred due to the charged surface surrounding the hydrophobic binding pocket, thereby preventing glutathione entry. Using umbelliprenin prodrugS, cell-based assays were done to show their promising cytotoxic activity. The paper presenting these findings has been finalized and published.
3) Development of ethylene biosensors: An ArM ethylene probe (AEP) was designed and developed. The concept behind this approach was to use the albumin scaffold to solubilize and protect a quenched ruthenium catalyst, which would react to produce fluorescence in the presence of the phytohormone ethylene. This probe was then used for the spatiotemporal detection of both exogenous- and endogenous-induced changes to ethylene biosynthesis in fruits and leaves. The paper presenting these findings has been finalized and published.
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Research Products
(7 results)
