Reaction-based fluorescent sensor for investigating mobile Zn[superscript 2+] in mitochondria of healthy versus cancerous prostate cells
Author(s)Chyan, Wen; Zhang, Daniel Y.; Lippard, Stephen J.; Radford, Robert J.
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Chelatable, mobile forms of divalent zinc, Zn(II), play essential signaling roles in mammalian biology. A complex network of zinc import and transport proteins has evolved to control zinc concentration and distribution on a subcellular level. Understanding the action of mobile zinc requires tools that can detect changes in Zn(II) concentrations at discrete cellular locales. We present here a zinc-responsive, reaction-based, targetable probe based on the diacetyled form of Zinpyr-1. The compound, (6-amidoethyl)triphenylphosphonium Zinpyr-1 diacetate (DA-ZP1-TPP), is essentially nonfluorescent in the metal-free state; however, exposure to Zn(II) triggers metal-mediated hydrolysis of the acetyl groups to afford a large, rapid, and zinc-induced fluorescence response. DA-ZP1-TPP is insensitive to intracellular esterases over a 2-h period and is impervious to proton-induced turn-on. A TPP unit is appended for targeting mitochondria, as demonstrated by live cell fluorescence imaging studies. The practical utility of DA-ZP1-TPP is demonstrated by experiments revealing that, in contrast to healthy epithelial prostate cells, tumorigenic cells are unable to accumulate mobile zinc within their mitochondria.
DepartmentMassachusetts Institute of Technology. Department of Chemistry
Proceedings of the National Academy of Sciences
National Academy of Sciences (U.S.)
Chyan, W., D. Y. Zhang, S. J. Lippard, and R. J. Radford. “Reaction-Based Fluorescent Sensor for Investigating Mobile Zn[superscript 2+] in Mitochondria of Healthy Versus Cancerous Prostate Cells.” Proceedings of the National Academy of Sciences 111, no. 1 (December 12, 2013): 143–148.
Final published version