Intensity-fading MALDI-TOF-MS: novel screening for ligand binding and drug discovery

Abstract Ligand discovery technologies largely rely on a primary screening for molecules showing affinity to a target, coupled with an approach to identify these molecules. Matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) is attracting increasing attention as a suitable analytical technique for ligand identification owing to its high sensitivity and capacity for discrimination, its fast analysis and its ease of automation. There is now a range of related strategies for drug discovery, including a novel MS-based methodology to screen noncovalent interactions between macromolecular targets (proteases) and peptide or organic ligands (protease inhibitors) called intensity-fading (IF) MALDI-TOF-MS.