Protein kinases are central regulators of cellular signaling, and their selective modulation provides a unique opportunity to better understand biological processes. Although many inhibitors have been developed, issues of selectivity remain a challenge, limiting the precision with which kinases can be studied. Different academic strategies have been proposed to address this challenge, including ATP-competitive inhibition, protein–protein interaction inhibition1,2, site-specific allosteric modulation3-5, and bisubstrate approaches6. This PhD project aims to explore innovative covalent strategies to design chemical probes7 that will allow selective and durable modulation of kinase activity.
Building on recent advances in covalent chemistry8-11, such as the reactivity of lysine side chains with electrophilic groups, we propose to investigate new scaffolds and anchoring strategies to optimize the selectivity of such interactions.