| 研究実績の概要 |
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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