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

Item Type:	Preprint
Title:	LiP-Quant, an automated chemoproteomic approach to identify drug targets in complex proteomes
Creators Name:	Piazza, I. and Beaton, N. and Bruderer, R. and Knobloch, T. and Barbisan, C. and Siepe, I. and Rinner, O. and de Souza, N. and Picotti, P. and Reiter, L.
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 small-molecule compounds. Current unbiased approaches cannot directly pinpoint the interaction surfaces between ligands and protein targets. To address his limitation we have developed a new drug target deconvolution approach based on limited proteolysis coupled with mass spectrometry that works across species including human cells (LiP-Quant). LiP-Quant features an automated data analysis pipeline and peptide-level resolution for the identification of any small-molecule binding sites, Here we demonstrate drug target identification by LiP-Quant across compound classes, including compounds targeting kinases and phosphatases. We demonstrate that LiP-Quant estimates the half maximal effective concentration (EC50) of compound binding sites 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.
Source:	bioRxiv
Title of Book:	LiP-Quant, an automated chemoproteomic approach to identify drug targets in complex proteomes
Publisher:	Cold Spring Harbor Laboratory Press
Article Number:	860072
Date:	1 December 2019
Official Publication:	https://doi.org/10.1101/860072

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