Mobile or loosely bound zinc participates in a variety of essential life processes ranging from neurotransmission to oocyte maturation. Fluorescent sensors that can be used to detect and image mobile zinc have proven to be valuable tools for studying complex biological systems. Many of these zinc sensors are built by derivatizing fluorophores with nitrogen-rich metal binding pockets. Zinc binding changes the chemical or electronic structure of the molecule in such a way as to enhance its fluorescence. Because these sensors typically bind zinc rapidly, investigators have little temporal control over the activity of the probe after it has been applied to a sample. The ability to selectively activate a zinc sensor in a particular cell during the course of an imaging experiment would greatly enhance the time resolution of this technique and is essential for studying the dynamics of zinc homeostasis. Here, we present strategies for overcoming this problem using activatable zinc sensors. We have developed two classes of zinc sensors that can be activated by either (i) a short pulse of UV light or (ii) an enzyme that can be transiently transfected into a cell. These probes are prepared by functionalizing the parent sensor with protecting groups in such a way as to render the caged probe insensitive to zinc. Enzymatic or photo-induced removal of the protecting groups restores the metal binding site, allowing for attendant changes in fluorescence. These activatable probes are suitable for imaging live cells and tissues. Applications of these probes in model systems will also be discussed. This work was supported by the National Institute of General Medical Sciences.

Activatable probes for the detection of mobile zinc in biology

252nd National Meeting (2016)

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