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Stay On Target: Deconvoluting Mixed Redox Messages through Precision Redox Targeting

The precisely timed and spatially regulated chemical signals are the essence of biochemical redox signaling. However, defining the precise biological impacts of localized signals that engage with specific protein targets under physiologic conditions has proven to be highly challenging. This abstract presents a unique set of proximity‐directed chemical tools that enables powerful interrogation into functional consequences of specific redox events through precision redox targeting in living systems (see, for example, Parvez et al. Nature Protocols 2016 11 2328; Long et al. 2016 Nature Chemical Biology Accepted). With this in vivo‐validated redox‐targeting toolset, we identify bona fide “first responders” sufficient to drive phenotypic responses at organismal level exemplified by zebrafish and C. elegans models. Our unique chemical biology toolset sets the stage for ruling in gain‐of‐function (or dominant loss‐of‐function) redox modifications and relating them to phenotype in an unbiased experiment that is not hampered by functional redundancy.