PXD047949

PXD047949 is an original dataset announced via ProteomeXchange.

Title	A probe-based target engagement assay for kinases in live cells
Description	Protein kinases are an important class of drug targets due to their crucial roles in almost every aspect of cellular function, such as cell growth, metabolism, proliferation, differentiation, migration, effector functions and cell death. Starting from the previously described covalent promiscuous kinase-targeting scaffold XO44, we evaluated alterations of the kinase binding core and on the enrichment moiety for kinase promiscuity and capturing in lysate and in live cells. By exchanging the alkyne click handle to a trans-cyclooctene, the more efficient Diels-Alder-Click reaction enabled the specific and displaceable enrichment of 95 kinases and 31 non-kinases from live cells. This improved tool enables a chemoproteomics assay to probe dose-dependent intracellular target engagement for probe-captured kinases for the kinase inhibitors dasatinib and dinaciclib. Further, we demonstrate that sepiapterin reductase and the multidrug resistance protein ABCC1 can be captured by this probe, suggesting these proteins as off-targets of kinase inhibitor scaffolds.
HostingRepository	PRIDE
AnnounceDate	2025-04-07
AnnouncementXML	Submission_2025-04-07_06:56:59.171.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ursula Glocker
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse; Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-19 07:16:39	ID requested
⏵ 1	2025-04-07 06:56:59	announced

10.1016/J.MCPRO.2025.100963;

submitter keyword: Cellular target engagement, Jurkat cells, LC-MS/MS

Marcus Bantscheff
contact affiliation	Cellzome - a GSK company
contact email	marcus.x.bantscheff@gsk.com
lab head
Ursula Glocker
contact affiliation	Cellzome - a GSK company
contact email	ursula.x.glocker@gsk.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/04/PXD047949

PRIDE project URI

• PRIDE
  1. PXD047949
     1. Label: PRIDE project
     2. Name: A probe-based target engagement assay for kinases in live cells