MALDI-TOF Mass Spectrometry-Based High-Throughput Screening for Inhibitors of the Cytosolic DNA Sensor cGAS

MALDI-TOF-Based Affinity Selection Mass Spectrometry for Automated Screening of Protein–Ligand Interactions at High Throughput

“…S13). 17,[33][34][35][36] Together, the results propose MALDI-TOF AS-MS as an attractive supplementary technology for affinity-based screening.…”

“…Compared to ESI-based MS, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS provides the sampling speed required for HTS and has been established as a valuable readout strategy for large-scale screening campaigns against the catalytic activity of enzymatic targets. [13][14][15][16][17] The adoption of the technology to interrogate protein-ligand interaction has been the subject of a number of proof-of-principle studies using ultrafiltration or affinity capture-based workflows to isolate protein-ligand complexes from incubation mixtures. [18][19][20] Although these studies have demonstrated the general feasibility of using MALDI-TOF MS for label-free small-molecule detection, a report of its combination with an HTS-capable automation platform is unprecedented.…”

High-throughput matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry–based deubiquitylating enzyme assay for drug discovery

“…This allowed the miniaturization and scalability of MALDI-TOF MS-based assays to 384 and 1,536 well formats. To date, MALDI-TOF MS-based assays have been established for a large variety of enzymes-including E3 ligases 62 , kinases 63,64 , phosphatases 65,66 , β-secretases (BACE1) 67 , histone demethylases and acetylcholinesterases 68 and cyclic GMP-AMP synthases 69 -and have been applied to the analysis of N-glycans [70][71][72] . The success of MALDI-TOF MS within HTS campaigns relies on several factors.…”

Fast Nanoliter‐Scale Cell Assays Using Droplet Microarray–Mass Spectrometry Imaging

“…[ 7–12 ] It is a versatile technology for the label‐free analysis of various classes of molecules, and is fast becoming established as a high‐throughput method for biochemical screening assays . [ 12–14 ] In non‐pharmacological applications, the utility of MALDI–MS for single cell metabolite analysis has been demonstrated, including in microcavity arrays. [ 15–17 ] Compared with commonly used fluorescence‐ and chemiluminescence‐based readouts, which require costly and non‐physiological secondary probes and therefore suffer from false‐positive and false‐negative results, [ 14 ] MALDI–MS is label‐free and allows multiple components to be detected simultaneously.…”

“…[ 20 ] Therefore, if MALDI–MS is to be used in a high throughput context, analytes or cells must be transferred from multi‐well plates onto special MALDI plates, or onto microarrays for mass spectrometry. [ 7,9,12–15,17,19 ] This step can be automated for measuring analytes in solution, but cannot be done to detect the biomolecules of intact treated cells directly on the platform. [ 14 ]…”