Covalent inhibitors are of high interest in chemical biology and drug discovery for expansion of the liganded proteome and for liganding challenging therapeutic targets. The majority of efforts to develop covalent inhibitors have focussed on the targeting of cysteine residues in the vicinity of protein pockets. However, to tackle the increasing number of genetically validated targets that drug discovery teams are presented with, approaches to covalent ligand discovery without reliance on cysteine are highly sought after. SFs offer the opportunity to target a broad repertoire of nucleophilic amino acids, and hence, are effective reactive moieties to consider for 'beyond cysteine' covalent inhibitors. To date, SF-containing chemical probes have been rationally designed based on structure-guided approaches; this typically entails the installation of a SF group onto a potent reversible scaffold. Here, we have demonstrated that sulfonyl fluoride reactive fragments offer an expedient approach to identify novel 'beyond-cysteine' covalent ligands.