Case Study: CARMS Screening in Cell Lysates

Many drug targets are unstable, difficult to purify, or only functional in their native biological context. While carbonic anhydrase is a well-characterised soluble enzyme, this case study explored a more demanding question: can a known binder be detected directly in cell lysate, eliminating the need for protein purification?

We applied CARMS to screen a 101-compound mixture against E. coli lysate containing carbonic anhydrase protein. A parallel screen was conducted against a control lysate lacking the protein. CARMS isolates intact protein-ligand complexes in the mass spectrometer and uses collision-induced dissociation to release and identify true binders, even in complex mixtures.

The known ligand was selectively detected in the lysate sample containing carbonic anhydrase but absent in the control, confirming target-specific binding. This study validated CARMS’ ability to detect binders directly in cell lysates—reducing assay development time and opening new avenues for screening low-purification or unstable targets.