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Studying electrophile signaling is marred by difficulties in parsing changes in pathway flux attributable to on-target, vis-& agrave;-vis off-target, modifications. By combining bolus dosing, knockdown, and Z- REX & mdash;a tool investigating on- target/on ...
The mechanism-of-action of many electrohilic drugs remains poorly understood. Here, the authors use a redox-targeting approach to elucidate the basis for the innate immune cell toxicity of dimethyl fumarate, showing that it modifies Keap1 to trigger mitoch ...
NATURE PORTFOLIO2021
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In this tutorial review, we compare and contrast the chemical mechanisms of electrophile/oxidant sensing, and the molecular mechanisms of signal propagation. We critically analyze biological systems in which these different pathways are believed to be mani ...
Here we provide a personal account of innovation and design principles underpinning a method to interrogate precision electrophile signaling that has come to be known as "REX technologies". This Account is framed in the context of trying to improve methods ...
If one considers chemical-biology toolsets that have had the greatest impact on numerous fields of life sciences over the most recent years, proximity-labeling tools, such as APEX, and Bio-ID arguably lead the way. This article reflects upon the current st ...
First established in the seventies, proteomics, chemoproteomics, and most recently, spatial/proximity-proteomics technologies have empowered researchers with new capabilities to illuminate cellular communication networks that govern sophisticated decision- ...
It is now clear that some cysteines on some proteins are highly tuned to react with electrophiles. Based on numerous studies, it is also established that electrophile sensing underpins rewiring of several critical signaling processes. These electrophile-se ...
For several years, drugs with reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving the drug-prote ...
CoVID-19 is a multi-symptomatic disease which has made a global impact due to its ability to spread rapidly, and its relatively high mortality rate. Beyond the heroic efforts to develop vaccines, which we do not discuss herein, the response of scientists a ...
Off-target effects continue to impede disease interventions, particularly when targeting a specific protein within a family of similar proteins, such as kinase isoforms that play tumor-subtype-specific roles in cancers. Exploiting the specific electrophili ...
