An Activity-Based Oxaziridine Platform for Identifying and Developing Covalent Ligands for Functional Allosteric Methionine Sites: Redox-Dependent Inhibition of Cyclin-Dependent Kinase 4

This paper presents a new methionine-directed activity-based protein profiling (ABPP) platform to identify and target functional methionine sites on proteins for covalent ligand discovery. Using Redox-Activated Chemical Tagging (ReACT) probes that target methionine residues, the authors identified three hyperreactive, ligandable methionine sites (M169, M264, M275) on the cancer-related protein cyclin-dependent kinase 4 (CDK4). They designed and synthesized a focused library of 179 oxaziridine fragments to screen against CDK4. Fragment 1oxF11 was identified as binding to the M169 site selectively over other CDK isoforms. <a href="https://medium.com/@axialxyz/an-activity-based-oxaziridine-platform-for-identifying-and-developing-covalent-ligands-for-cbf0cdbcdad9">Learn More</a>