Bruker PharmaPulse HTS: fast drug candidate screening with MALDI TOF-MS

High-throughput screening (HTS) is widely used for finding new drug candidates by screening large compound libraries against targets for a particular disease. For example, compounds will be screened for their ability to inhibit or stimulate enzyme activity. The more versatile and robust the readout technology the greater the impact on screening. Traditional detection technologies used for HTS includes, e.g., Time-Resolved Fluorescence Energy Transfer (TR-FRET), Fluorescence Intensity (FI), luminescence, and radioactivity-based methods. Most of these require the use of a “label” in order to “read” the reactions which increases cost and complexity. Labels can also affect the results leading to false positives/negatives. “Label-Free” HTS detection technologies are therefore highly desirable to accelerate assay development, reduce complexity of screening, and potentially minimize artifacts from interference with the label. Here we will present a method based on MALDI MS, which allows for fast assay development and eliminates the need to develop antibodies or fluorescent labels. MALDI PharmaPulse is a complete mass spectrometry based screening solution designed to accelerate all phases of drug discovery. The system offers the advantage of true label-free detection of native substrates and products in functional biochemical assays. An ultrafast MALDI-TOF system delivers analytical results in less than 1 second per sample making it uniquely suited for HTS. Robust automation and workflows enables more than 50,000 samples screened per day. Proof of concept with JMJD2c histone demethylase and acetylcholinesterase in 1536-well format will be presented.

Keywords: Drug candidate screening, MALDI TOF-MS, high-throughput screening, label-free screening technology.

References:

[1] Haslam C, Hellicar J, Dunn A, Fuetterer A, Hardy N, Marshall P, Paape R, Pemberton M, Resemannand A, Leveridge M. The evolution of MALDI-TOF mass spectrometry toward ultra-high-throughput screening: 1536-well format and beyond. J Biomol Screen 2016; 21: 176 – 186