All three probes (2j-l) were found to enrich multiple proteins by comparison to the DMSO control (523, 501, and 447 respectively, log2 ratio ≥0.58, p-value ≤0.05, #unique peptides ≥2), highlighting the promiscuity of the reactive fragments in this environment. A good correlation was observed between all three probes and the proteins enriched, indicating that most of the enrichment was driven by the SF moiety, rather than the fragment portion of the probes (Fig. ). The most significantly enriched proteins included: FABP5, APMAP, and CRABP2. Previous reports identified that FABP5 and CRABP2 were targeted by an arylfluorosulfate probe by reaction at a tyrosine residue in each of these proteins. While some enrichment of CAII was observed for 2j and 2k, this was poorly resolved amongst the many other enriched proteins. To further investigate CAII engagement of the sulfonamide-containing active probes (2j and 2k) in live cells, we compared the enriched proteins to those enriched by the methoxy-containing negative control (2l). This highlighted CAII as one of the few differentially enriched proteins, suggesting that the aryl sulfonamide fragment hits were driving cellular engagement of CAII (Fig. &).