Monitoring Protein-Drug Interactions with Mass Spectrometry and Proteolysis Protein Mass Mapping as a Drug Assay

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Abstract
Presented is a new approach for assaying the effects of drug candidates against protein targets. Human rhinovirus, HRV14, has been analyzed in the presence of both known and potential antiviral drug agents using enzymatically active mass spectrometer sample plates. The combination of automated mass spectrometry with proteolytic digestion provides for the rapid, high-throughput, and sensitive screening of protein-drug interactions. Multiple drug candidates can be assayed from MALDI sample plates containing 100 wells and, to further increase the number of drugs assayed, multiple drugs can be pooled into each solution (10 candidates per well, 1000 candidates per plate). Wells producing spectra indicative of drug activity can be further analyzed to discern the active compound or be tested with alternative assays.