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

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

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AmberGen, Inc., 313 Pleasant Street, Watertown, MA 02472, United States.
Molecular Biophysics Laboratory, Department of Physics and Photonics Center, Boston University, Boston, MA 02215, United States.


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.

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