In conclusion, we have developed XL-RaPID, a generally applicable strategy to isolate photoactivatable ligands to a target protein of interest. Application of XL-RaPID to BRD3-BD2 resulted in pBpacontaining cyclic peptide ligands that efficiently and selectively photocrosslinked with their target, even in the context of complex cell lysates. Our peptides showed substantially weaker binding affinities than is usually found in RaPID screens, suggesting that crosslinker positioning is likely more important than affinity, thus highlighting the power of selecting directly for photocrosslinking efficiency rather than retrofitting a crosslinking moiety to a known ligand. In the future, the same approach could be used to produce photocrosslinking ligands containing other warheads compatible with in vitro translation, such as diazirines. Further we envisage that this same modified affinity panning protocol could be applied more widely to the discovery of covalent cyclic peptide ligands from mRNA display libraries incorporating reactive covalent warheads.