Multiplexed Screening of Thousands of Natural Products for Protein-Ligand Binding in Native Mass Spectrometry.

Autor:	Nguyen GTH; School of Chemistry, University of New South Wales, Sydney, New South Wales 2052, Australia., Bennett JL; School of Chemistry, University of New South Wales, Sydney, New South Wales 2052, Australia., Liu S; School of Chemistry, University of New South Wales, Sydney, New South Wales 2052, Australia., Hancock SE; School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia., Winter DL; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia., Glover DJ; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia., Donald WA; School of Chemistry, University of New South Wales, Sydney, New South Wales 2052, Australia.
Jazyk:	angličtina
Zdroj:	Journal of the American Chemical Society [J Am Chem Soc] 2021 Dec 22; Vol. 143 (50), pp. 21379-21387. Date of Electronic Publication: 2021 Dec 10.
DOI:	10.1021/jacs.1c10408
Abstrakt:	The structural diversity of natural products offers unique opportunities for drug discovery, but challenges associated with their isolation and screening can hinder the identification of drug-like molecules from complex natural product extracts. Here we introduce a mass spectrometry-based approach that integrates untargeted metabolomics with multistage, high-resolution native mass spectrometry to rapidly identify natural products that bind to therapeutically relevant protein targets. By directly screening crude natural product extracts containing thousands of drug-like small molecules using a single, rapid measurement, we could identify novel natural product ligands of human drug targets without fractionation. This method should significantly increase the efficiency of target-based natural product drug discovery workflows.
Databáze:	MEDLINE
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