Solution-Based Indirect Affinity Selection Mass Spectrometry—A General Tool For High-Throughput Screening Of Pharmaceutical Compound Libraries

We show here that an automated solution-based affinity selection mass spectrometry (ASMS) system can be built exclusively from commercially available parts. The value of this technology lies in the throughput (similar to 1 x 10(5) compounds/day) coupled with a low hit rate. The system, being a binding assay, requires little development time yielding a fast timeline between target availability and hit identification. In addition, the use of exact mass simplifies the hit identification. We demonstrate this system using carbonic anhydrase as the target and a library of 144,000 proprietary compounds.