Proteomics

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Tissue Thermal Proteome Profiling

ABSTRACT: We introduce tissue Thermal Proteome Profiling (tissue-TPP) which enables the discovery of drug targets and off-targets as well as measurements of target occupancy in tissue samples derived from dosed animals. Here we report the first proteome-wide thermal stability map of tissues and organ-specific target profiles of the non-covalent histone deacetylase inhibitor, panobinostat. In addition, we devised blood-CETSA/TPP to monitor target and off-target engagement directly in whole blood.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Nils Kurzawa  

LAB HEAD: Marcus Bantscheff

PROVIDER: PXD015397 | Pride | 2020-01-07

REPOSITORIES: Pride

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Publications

Monitoring drug-target interactions with methods such as the cellular thermal-shift assay (CETSA) is well established for simple cell systems but remains challenging in vivo. Here we introduce tissue thermal proteome profiling (tissue-TPP), which measures binding of small-molecule drugs to proteins in tissue samples from drug-treated animals by detecting changes in protein thermal stability using quantitative mass spectrometry. We report organ-specific, proteome-wide thermal stability maps and d  ...[more]

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