Self-Immolative Probes for Spatial Mapping of Cellular Reactive Oxygen Species

Cellular reactive oxygen species (ROS) are important metabolites derived from dioxygen (O2) that are a double-edged sword for living organisms: though uncontrolled ROS production and distribution can lead to oxidative damage of nucleic acids, lipids, and proteins, causing disease states, emerging evidence points toward ROS’ role as critical signaling molecules that mediate protein phosphorylation and transcription factor activity. Progress in the past decade has yielded small molecule fluorophores capable of monitoring ROS production in living cells, providing biologists with a powerful toolkit to visualize ROS production in real time. However, these small molecules are free to diffuse through the cell, greatly limiting the spatial information they can provide about the genesis of cellular ROS.

Drawing on established chemistry in the field of bioconjugation, as well as new chemistry established in the Domaille lab, we are developing new chemical triggers that covalently tag proteins directly involved in ROS generation. This will enable us to better understand the spatial distribution of cellular ROS so that we can identify key players in ROS signaling pathways.

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