Proteome-wide drug screening using mass spectrometric imaging of bead-arrays

Sci Rep. 2016 May 19:6:26125. doi: 10.1038/srep26125.


A fundamental challenge in the drug discovery process is to develop compounds with high efficacy and minimal side-effects. We describe a new approach to proteome-wide drug screening for detection of on- and off-target binding which combines the advantages of mass spectrometry with microarray technology. The method involves matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) of agarose micro-beads randomly arrayed at high-density in custom micro-well plates. Each bead carries a unique protein target and a corresponding photocleavable mass-tag for coding (PC-Mass-Tag). Compounds bound to specific protein beads and a photo-released coding PC-Mass-Tag are detected simultaneously using MALDI-MSI. As an initial demonstration of this approach, two kinase-targeted drugs, Dasatinib and Brigatinib (AP26113), were simultaneously screened against a model 50-member kinase-bead library. A MALDI-MSI scan performed at the equivalent density of 495,000 beads in the footprint of a microscope slide yielded 100% sensitivity for detecting known strong interactions with no false positives.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Dasatinib / metabolism
  • Drug Evaluation, Preclinical / methods*
  • Mass Spectrometry / methods*
  • Microspheres
  • Organophosphorus Compounds / metabolism
  • Protein Array Analysis / methods*
  • Protein Binding
  • Protein Kinase Inhibitors / metabolism
  • Proteome / analysis*
  • Pyrimidines / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Organophosphorus Compounds
  • Protein Kinase Inhibitors
  • Proteome
  • Pyrimidines
  • brigatinib
  • Dasatinib