Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep07724
Title: Multiplex imaging and cellular target identification of kinase inhibitors via an affinity-based proteome profiling approach
Authors: Su Y. 
Pan S. 
Li Z. 
Li L. 
Wu X. 
Hao P.
Sze S.K.
Yao S.Q. 
Keywords: molecular probe
protein kinase inhibitor
proteome
affinity chromatography
chemistry
HeLa cell line
human
liquid chromatography
metabolism
molecular imaging
molecular probe
molecularly targeted therapy
procedures
proteomics
tandem mass spectrometry
Chromatography, Affinity
Chromatography, Liquid
HeLa Cells
Humans
Molecular Imaging
Molecular Probes
Molecular Targeted Therapy
Protein Kinase Inhibitors
Proteome
Proteomics
Tandem Mass Spectrometry
Issue Date: 2015
Citation: Su Y., Pan S., Li Z., Li L., Wu X., Hao P., Sze S.K., Yao S.Q. (2015). Multiplex imaging and cellular target identification of kinase inhibitors via an affinity-based proteome profiling approach. Scientific Reports 5 : 7724. ScholarBank@NUS Repository. https://doi.org/10.1038/srep07724
Abstract: MLN8237 is a highly potent and presumably selective inhibitor of Aurora kinase A (AKA) and has shown promising antitumor activities. Like other kinase inhibitors which target the ATP-binding site of kinases, MLN8237 might be expected to have potential cellular off-targets. Herein, we report the first photoaffinity-based, small molecule AKA probe capable of both live-cell imaging of AKA activities and in situ proteome profiling of potential off-targets of MLN8237 (including AKA-associating proteins). By using two mutually compatible, bioorthogonal reactions (copper-catalyzed azide-alkyne cycloaddition chemistry and TCO-tetrazine ligation), we demostrate small molecule-based multiplex bioimaging for simultaneous in situ monitoring of two important cell-cycle regulating kinases (AKA and CDK1). A broad range of proteins, as potential off-targets of MLN8237 and AKA's-interacting partners, is subsequently identified by affinity-based proteome profiling coupled with large-scale LC-MS/MS analysis. From these studies, we discover novel AKA interactions which were further validated by cell-based immunoprecipitation (IP) experiments.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/174577
ISSN: 2045-2322
DOI: 10.1038/srep07724
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