Photoaffinity labelling has proved useful for the capture of reversible ligand-protein interactions. Upon irradiation with UV light, photoreactive warheads can covalently crosslink to proximal protein residues, providing a broad method for the covalent capture of reversible ligand-protein binding. Cravatt and co-workers recently reported the use of photoreactive fragments for the identification of fragment-protein interactions in live cells. This proof-of-concept study highlights an opportunity to screen libraries of fragments in cells to build a fragment-protein interaction database across the proteome. However, the current throughput and sensitivity of the MSbased proteomic readout, as well as the large dynamic range of the proteome, limits the broad adoption of this approach. We hypothesised that the use of photoreactive fragment libraries in a biochemical setting would improve the throughput and enable targeted screening against proteins of interest. Such an approach would build upon electrophilic fragments, with the advantage of being applicable to all protein pockets.