Fig. 4: Identification and validation of ligands against CAIX.

a SEL 1, 2 and 3 were panned in duplicates against immobilized CAIX. While MS1 features were consistently detected in both duplicates, annotated hits showed only a moderate overlap (Supplementary Figs. 16, 17). After analysis of the selected samples via nanoLCMS/MS and COMET, we plotted building block frequencies for each library scaffold and position. Aromatic sulfonamides were significantly enriched from all libraries (p < 0.0001, see Supplementary Fig. 18). b Examples of hit compounds: the chromatograms show extracted ion counts using a 5 ppm accuracy of their corresponding masses in the CAIX sample and bead-only control, demonstrating their selective enrichment. Biotinylated versions of these examples were resynthesized, and BLI association/dissociation curves confirmed their binding to CAIX. Source data are provided as a Source Data file.