The ability to detect, image, and quantify proteins, particularly enzymes linked to cellular disease state, is an actively investigated area due to its direct impact on fundamental and applied studies of cell behavior, as well as long-term potential to provide details of cellular function in diseased tissues. Successful fluorescence cellular imaging of active enzymes in live cells requires development of enzyme-reactive probes capable of having their fluorescence signature selectively altered by the target enzyme. We describe here the synthesis, characterization, and implementation of a family of molecular probes that respond to human oxidoreductase and glycoside hydrolase activity levels in vitro and in vivo. The probes are either fluorescently silent and then become highly fluorescent, or their native fluorescence response at a given energy shifts to another wavelength, as a result of enzymatically-driven removal of trigger groups on a given dye.  The behavior of the probes in the presence of human enzyme activity, both outside of and within human cells, including cancer cells, is presented.

Switchable molecular fluorescent probes for detection and imaging of enzymes linked to disease

255th National Meeting (2018)

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