LiP-Quant, an automated chemoproteomic approach to identify drug targets in complex proteomes, p2

ABSTRACT: Chemoproteomics is a key technology to characterize the mode of action of drugs, as it directly identifies the protein targets of bioactive compounds and aids in developing optimized leads. We have developed a drug target deconvolution approach with an automated data analysis pipeline, based on limited proteolysis coupled with mass spectrometry that works across species including in human cells (LiP-Quant). Here we demonstrate drug target identification by LiP-Quant across compound classes, including with drugs targeting kinases and phosphatases . We demonstrate that LiP-Quant identifies drug binding sites, a unique feature of this approach, and that it can be used to estimate drug EC50s in whole cell lysates . LiP-Quant identifies targets of both selective and promiscuous drugs and correctly discriminates drug binding to homologous proteins. We finally show that the LiP-Quant technology identifies targets of a novel research compound of biotechnological interest.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hela Cell

SUBMITTER: Ilaria Piazza  

LAB HEAD: Dr. Lukas Reiter

PROVIDER: PXD018204 | Pride | 2020-09-09

REPOSITORIES: Pride