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A far-red emitting probe for unambiguous detection of mobile zinc in acidic vesicles and deep tissue
Authors:Pablo Rivera-Fuentes  Alexandra T Wrobel  Melissa L Zastrow  Mustafa Khan  John Georgiou  Thomas T Luyben  John C Roder  Kenichi Okamoto  Stephen J Lippard
Institution:a Department of Chemistry , Massachusetts Institute of Technology , Cambridge , MA 02139 , USA . Email: ;b Lunenfeld-Tanenbaum Research Institute , Mount Sinai Hospital , Toronto , ON M5G 1X5 , Canada ;c Department of Molecular Genetics , Faculty of Medicine , University of Toronto , Toronto , ON M5S 1A8 , Canada
Abstract:Imaging mobile zinc in acidic environments remains challenging because most small-molecule optical probes display pH-dependent fluorescence. Here we report a reaction-based sensor that detects mobile zinc unambiguously at low pH. The sensor responds reversibly and with a large dynamic range to exogenously applied Zn2+ in lysosomes of HeLa cells, endogenous Zn2+ in insulin granules of MIN6 cells, and zinc-rich mossy fiber boutons in hippocampal tissue from mice. This long-wavelength probe is compatible with the green-fluorescent protein, enabling multicolor imaging, and facilitates visualization of mossy fiber boutons at depths of >100 μm, as demonstrated by studies in live tissue employing two-photon microscopy.
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