The SF-based reactive fragment screening approach was developed in two stages: first, the development of an appropriate SF fragment library, and second, the application of this library in screens against three protein targets. A modular library was employed by linking a diverse set of amine-functionalised fragments to a SFcontaining reactive moiety. Three SFs were selected that spanned a range of intrinsic reactivities, based on previous profiling of SF functionalities. These included aromatic sulfonyl fluorides 1 (meta-substituted) and 2 (para-substituted with a methylene spacer), as well as sulfamoyl fluoride 3 (azetidine-linked) (Fig. ).