Lu Zhang, Jeffrey G Martin, Benbo Gao, Weike Zeng, Shalise Couvertier, Douglas S Johnson
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Chemoproteomic Profiling of Clickable Fumarate Probes for Target Identification and Mechanism of Action Studies.
Dimethyl fumarate (DMF) is an established oral therapy for multiple sclerosis worldwide. Although the clinical efficacy of these fumarate esters has been extensively investigated, the mode of action and pharmacokinetics of fumarates have not been fully elucidated due to their broad-spectrum reactivity and complex metabolism in vivo. To better understand the mechanism of action of DMF and its active metabolite, monomethyl fumarate (MMF), we designed and utilized clickable probes to visualize and enrich probe-modified proteins. We further perform quantitative chemoproteomics analysis for proteome-wide target identification and validate several unique and shared targets of DMF and MMF, which provide insight into the reactivity, selectivity, and target engagement of fumarates.
期刊介绍：
ACS Chemical Biology provides an international forum for the rapid communication of research that broadly embraces the interface between chemistry and biology.
The journal also serves as a forum to facilitate the communication between biologists and chemists that will translate into new research opportunities and discoveries. Results will be published in which molecular reasoning has been used to probe questions through in vitro investigations, cell biological methods, or organismic studies.
We welcome mechanistic studies on proteins, nucleic acids, sugars, lipids, and nonbiological polymers. The journal serves a large scientific community, exploring cellular function from both chemical and biological perspectives. It is understood that submitted work is based upon original results and has not been published previously.
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