Fluorescent sensors that can detect and image mobile zinc have proved valuable tools for studying complex biological systems. Many such zinc sensors incorporate fluorophores with nitrogen-rich metal binding pockets. Zinc binding changes the chemical and/or electronic structure of the molecule in such a way as to enhance its fluorescence. Because these sensors typically bind zinc rapidly, there has been little temporal control over the activity of the probe after its application to a sample. The ability to trigger the activity of a zinc sensor in cells during imaging experiments would add the dimension of time resolution to the measurement, a feature that is essential for studying the dynamics of zinc homeostasis. Here, we present strategies for achieving this goal through the use of activatable zinc sensors. In particular, we introduce two classes of zinc sensors that can be triggered either by (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 that render the 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 caged probes are suitable for imaging live cells and tissues, as will be demonstrated. Applications will be described. This work was supported by the US National Institute of General Medical Sciences through a grant to SJL and a Postdoctoral Fellowship to JMG.<br/> <br/>

Strategies and results for controlled activation of small-molecule zinc sensors in cells

255th National Meeting (2018)

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