Development of a target identification approach using native mass spectrometry

Abstract A key step in the development of new pharmaceutical drugs is the identification of the molecular target and distinguishing this from all other gene products that respond indirectly to the drug. Target identification remains a crucial process and a current bottleneck for advancing hits throu...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Miaomiao Liu, Wesley C. Van Voorhis, Ronald J. Quinn
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/79735f1a181546f9a030b3da081e8bf6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:79735f1a181546f9a030b3da081e8bf6
record_format	dspace
spelling	oai:doaj.org-article:79735f1a181546f9a030b3da081e8bf62021-12-02T10:48:22ZDevelopment of a target identification approach using native mass spectrometry10.1038/s41598-021-81859-42045-2322https://doaj.org/article/79735f1a181546f9a030b3da081e8bf62021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81859-4https://doaj.org/toc/2045-2322Abstract A key step in the development of new pharmaceutical drugs is the identification of the molecular target and distinguishing this from all other gene products that respond indirectly to the drug. Target identification remains a crucial process and a current bottleneck for advancing hits through the discovery pipeline. Here we report a method, that takes advantage of the specific detection of protein–ligand complexes by native mass spectrometry (MS) to probe the protein partner of a ligand in an untargeted method. The key advantage is that it uses unmodified small molecules for binding and, thereby, it does not require labelled ligands and is not limited by the chemistry required to tag the molecule. We demonstrate the use of native MS to identify known ligand–protein interactions in a protein mixture under various experimental conditions. A protein–ligand complex was successfully detected between parthenolide and thioredoxin (PfTrx) in a five-protein mixture, as well as when parthenolide was mixed in a bacterial cell lysate spiked with PfTrx. We provide preliminary data that native MS could be used to identify binding targets for any small molecule.Miaomiao LiuWesley C. Van VoorhisRonald J. QuinnNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Miaomiao Liu Wesley C. Van Voorhis Ronald J. Quinn Development of a target identification approach using native mass spectrometry
description	Abstract A key step in the development of new pharmaceutical drugs is the identification of the molecular target and distinguishing this from all other gene products that respond indirectly to the drug. Target identification remains a crucial process and a current bottleneck for advancing hits through the discovery pipeline. Here we report a method, that takes advantage of the specific detection of protein–ligand complexes by native mass spectrometry (MS) to probe the protein partner of a ligand in an untargeted method. The key advantage is that it uses unmodified small molecules for binding and, thereby, it does not require labelled ligands and is not limited by the chemistry required to tag the molecule. We demonstrate the use of native MS to identify known ligand–protein interactions in a protein mixture under various experimental conditions. A protein–ligand complex was successfully detected between parthenolide and thioredoxin (PfTrx) in a five-protein mixture, as well as when parthenolide was mixed in a bacterial cell lysate spiked with PfTrx. We provide preliminary data that native MS could be used to identify binding targets for any small molecule.
format	article
author	Miaomiao Liu Wesley C. Van Voorhis Ronald J. Quinn
author_facet	Miaomiao Liu Wesley C. Van Voorhis Ronald J. Quinn
author_sort	Miaomiao Liu
title	Development of a target identification approach using native mass spectrometry
title_short	Development of a target identification approach using native mass spectrometry
title_full	Development of a target identification approach using native mass spectrometry
title_fullStr	Development of a target identification approach using native mass spectrometry
title_full_unstemmed	Development of a target identification approach using native mass spectrometry
title_sort	development of a target identification approach using native mass spectrometry
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/79735f1a181546f9a030b3da081e8bf6
work_keys_str_mv	AT miaomiaoliu developmentofatargetidentificationapproachusingnativemassspectrometry AT wesleycvanvoorhis developmentofatargetidentificationapproachusingnativemassspectrometry AT ronaldjquinn developmentofatargetidentificationapproachusingnativemassspectrometry
_version_	1718396656935763968

Development of a target identification approach using native mass spectrometry

Ejemplares similares