In vitro display technologies such as mRNA display and phage display are ideal for this purpose as they allow the generation and screening of large, randomised libraries of peptides incorporating unnatural side chain chemistries. For example, such libraries have recently been applied to the development of photoswitchable ligands through incorporation of an azobenzene group, as well as the identification of covalent inhibitors by introducing reactive electrophilic warheads. The RaPID (random non-standard peptide integrated discovery) system is particularly well suited to this due to the ability to incorporate a wide variety of unnatural chemistries into peptides using flexible in vitro translation (FIT). Here, we report an mRNA display strategy, photocrosslinking-RaPID (XL-RaPID), to evolve peptides that undergo efficient covalent modification with their target of choice upon light activation (Figure ). Having first adapted the affinity panning step to isolate only covalent target-binding peptides, we applied XL-RaPID screening against a model target, the second bromodomain of BRD3 (BRD3-BD2).