PXD068999

PXD068999 is an original dataset announced via ProteomeXchange.

Title	Unsaturated phosphorus electrophiles to probe protein tyrosine phosphatases
Description	Protein tyrosine phosphatases (PTPs) represent an important pharmacological target. To this end, broad spectrum electrophilic, phosphotyrosine-mimicking probes have been developed to covalently capture the catalytic site of these enzymes. Despite these efforts, there is still a high demand for synthetically straightforward accessible PTP-probes with high target selectivity. Unsaturated phosphorus-(V) (P(V)) compounds have recently emerged as powerful cysteine-selective bioconjugation reagents (P5-labeling). Here, we introduce ethynyl-substituted aryl-phosphonamidic and -phosphonic acids as phosphotyrosine mimics, which serve as active site-directed, covalent probes for tyrosine phosphatases. We show that these P(V)-electrophiles can be easily incorporated into a peptide sequence, allowing proximity-enabled reactivity and selective targeting of the catalytic cysteine of an interacting phosphatase as exemplified for PTP1B. Both, ethynyl phosphonamidic and phosphonic acid show no reactivity towards non-affine cysteines, though the phosphonamidic acid probe was notably less reactive toward its intended target. Proteomics experiments in human cell lysates demonstrated that the phosphonic acid probe selectively labels its interacting phosphatase in the human proteome. Our study highlights a versatile strategy to obtain remarkably precise peptide-based PTP-probes, thereby enabling the characterization of phosphatase interactions with high specificity.
HostingRepository	PRIDE
AnnounceDate	2026-03-03
AnnouncementXML	Submission_2026-03-03_07:10:33.524.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Max Ruwolt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Exploris 480; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-30 06:31:56	ID requested
⏵ 1	2026-03-03 07:10:34	announced

10.1002/ANIE.202521902;

submitter keyword: None

Christian Hackenberger
contact affiliation	Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) Robert-Rössle-Strasse 10, 13125 Berlin (Germany) Department of Chemistry, Humboldt Universität zu Berlin Brook-Taylor-Straße 2, 12489 Berlin (Germany)
contact email	Hackenbe@fmp-berlin.de
lab head
Max Ruwolt
contact affiliation	Leibniz-Forschungsinstitut for Molecular Pharmacology
contact email	ruwolt@fmp-berlin.de
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/2026/03/PXD068999

PRIDE project URI

• PRIDE
  1. PXD068999
     1. Label: PRIDE project
     2. Name: Unsaturated phosphorus electrophiles to probe protein tyrosine phosphatases