Robust methods that monitor enzyme activity and inhibitor potency are crucial to drug discovery and development. Over the past 20 years, mass spectrometric methods have increasingly been used to measure enzyme activity and kinetics. However, for rapid screening of inhibitory compounds, various forms of fluorescence and chemiluminscence readout have continued to dominate the market. As the sensitivity, speed, and miniaturization of mass spectrometry methods continue to advance, opportunities to couple mass spectrometry with screening will continue to come to the forefront. To appreciate the tremendous potential for MS-based screening assays, it becomes necessary to understand the current state of capabilities in this arena. Thus, this review is intended to capture how mass spectrometry for studying enzymes activity has progressed from simple qualitative questions (i.e., is the product detected?) to quantitative measures of enzyme activity and kinetics and then as a tool for rapidly screening inhibitory compounds as an alternative to current methods of high throughput drug screening.
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