A library approach to rapidly discover photoaffinity probes of the mRNA decapping scavenger enzyme DcpS

Despite its diverse applications, such as identification of the protein binding partners of small molecules and investigation of intracellular drug–target engagement, photoaffinity labelling (PAL) is intrinsically challenging, primarily due to the difficulty in discovering functionally active photoaffinity probes. Here we describe the creation of a chemoproteomic library to discover a novel photoaffinity probe for DcpS, an mRNA decapping enzyme that is a putative target for Spinal Muscular Atrophy. This library approach expedites the discovery of photoaffinity probes and expands the chemical biology toolbox to include RNA cap-binding proteins.