Prodrug Activation by Gold Artificial Metalloenzyme-Catalyzed Synthesis of Phenanthridinium Derivatives via Hydroamination. Chang, T. C., Vong, K., Yamamoto, T., & Tanaka, K. Angewandte Chemie - International Edition, 60(22):12446–12454, 2021.
doi  abstract   bibtex   
An emerging approach in the field of targeted drug delivery is the establishment of abiotic metal-triggered prodrug mechanisms that can control the release of bioactive drugs. Currently, the design of prodrugs that use abiotic metals as a trigger relies heavily on uncaging strategies. Here, we introduce a strategy based on the gold-catalyzed activation of a phenanthridinium-based prodrug via hydroamination under physiological conditions. To make the prodrug strategy biocompatible, a gold artificial metalloenzyme (ArM) based on human serum albumin, rather than the free gold metal complex, was used as a trigger 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 in vitro. The drug synthesized via the gold ArM exerted a therapeutic effect in cell-based assays, highlighting the potential usefulness of the gold ArM in anticancer applications.
@article{chang_prodrug_2021,
	title = {Prodrug {Activation} by {Gold} {Artificial} {Metalloenzyme}-{Catalyzed} {Synthesis} of {Phenanthridinium} {Derivatives} via {Hydroamination}},
	volume = {60},
	issn = {15213773},
	doi = {10.1002/anie.202100369},
	abstract = {An emerging approach in the field of targeted drug delivery is the establishment of abiotic metal-triggered prodrug mechanisms that can control the release of bioactive drugs. Currently, the design of prodrugs that use abiotic metals as a trigger relies heavily on uncaging strategies. Here, we introduce a strategy based on the gold-catalyzed activation of a phenanthridinium-based prodrug via hydroamination under physiological conditions. To make the prodrug strategy biocompatible, a gold artificial metalloenzyme (ArM) based on human serum albumin, rather than the free gold metal complex, was used as a trigger 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 in vitro. The drug synthesized via the gold ArM exerted a therapeutic effect in cell-based assays, highlighting the potential usefulness of the gold ArM in anticancer applications.},
	number = {22},
	journal = {Angewandte Chemie - International Edition},
	author = {Chang, Tsung Che and Vong, Kenward and Yamamoto, Tomoya and Tanaka, Katsunori},
	year = {2021},
	pmid = {33719151},
	keywords = {antitumor agents, gold catalysts, metalloenzymes, phenanthridinium, prodrugs},
	pages = {12446--12454},
}

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