Localis-rex: a new tool for studying electrophile signaling

A team of researchers led by Professor Yimon Aye at EPFL's School of Basic Sciences has developed a new screening method to explore an important biological process known as electrophile signaling. In general, an electrophile is a highly reactive compound that -seeks- to bond with atoms or other molecules that have an available electron pair. In the buzzing hive of activity that is the cell, electrophile signaling is a process that regulates the signaling properties of proteins. Electrophile signaling is also directly related to drug-target discovery and in our understanding of drug mode of action. In fact, there is an entire field of pharmacology that aims to improve the efficacy of certain drugs by adding electrophilic -parts- to them. Intriguingly, as the proteins move across the cell's subcellular compartments, they may encounter different reactive small-molecule metabolites, which are low-molecular weight compounds, typically involved in a biological process as a substrate or product. Some of these compounds are themselves electrophilic. Thus, it is interesting to ponder how a specific protein's -electrophile-sensing- properties may change across different parts of the cell. In 2021, Aye's group developed an innovative chemical method to study the biological mechanisms of the electrophilic drug Tecfidera, which is used to treat multiple sclerosis. Now, the team has developed a new tool, named -Localis-rex-, that allowed them to delve deeper into electrophile biology and address some unanswered questions in the field. The study is published in PNAS . Localis-rex: solving electrophile signaling mysteries