Thermal proteome profiling efficiently identifies ribosome destabilizing oxazolidinones

Christina Nöcker, Nadine Kaiser, Daniel Foley, Sonja Sievers, Petra Janning, Herbert Waldmann*, Luca Laraia*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Identifying the targets of bioactive small molecules is a challenging endeavor for which no general solution currently exists. Classical affinity purification experiments suffer from the need to functionalise a bioactive compound and link it to a solid support, which may interfere with target binding. A modern mass spectrometry-based proteomics technique that has partially circumvented this problem is thermal proteome profiling (TPP), which determines the effect of an unmodified small molecule on the thermal stability of the whole proteome simultaneously. Here, we use TPP to identify the mode-of-action of a newly-discovered autophagy inhibitor based on oxazolidinones often employed as chiral auxiliaries. Surprisingly, a significant portion of all ribosomal proteins were found to be destabilized by the inhibitor, highlighting the utility of this technology for determining a challenging mode-of-action.
Original languageEnglish
Article number132118
Publication statusPublished - 2021


  • Oxazolidinones
  • autophagy
  • target identification
  • thermal proteome profiling


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