PXD058896

PXD058896 is an original dataset announced via ProteomeXchange.

Title	Identification of Sulphostin targets unsig competitive ABPP
Description	Covalent chemical probes and drugs combine unique pharmacologic properties with the availability of straightforward compound profiling technologies via chemoproteomic platforms. These advantages have fostered the development of suitable electrophilic ‘warheads’ for systematic covalent chemical probe discovery. Despite undisputable advances in the last years, the targeted development of proteome-wide selective covalent probes such as for dipeptidyl peptidase (DPP) 8 and 9 (DPP8/9), intracellular serine hydrolases of the pharmacologically relevant dipeptidyl peptidase 4 activity/structure homologues (DASH) family, however, remains a challenge. Here, we show the exploration of the natural product Sulphostin, a DPP4 inhibitor, as a starting point for DPP8/9 inhibitor development. The generation of Sulphostin-inspired N-phosphonopiperidones leads to derivatives with improved DPP8/9 inhibitory potency, an enhanced proteome-wide selectivity and confirmed DPP8/9 engagement in cells, thereby representing that structural fine-tuning of the warhead’s leaving group may represent a straightforward strategy for achieving target selectivity in exoproteases such as DPPs.
HostingRepository	PRIDE
AnnounceDate	2025-02-25
AnnouncementXML	Submission_2025-02-24_23:35:57.734.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Farnusch Kaschani
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-16 01:18:42	ID requested
⏵ 1	2025-02-24 23:35:58	announced

Dataset with its publication pending

submitter keyword: inhibitor development, natural product, dipeptidyl peptidase,Activity-based protein profiling, target identification

Farnusch Kaschani
contact affiliation	Analytics Core Facility Essen (ACE), Chemische Biologie, Universität Duisburg-Essen, ZMB, Germany
contact email	farnusch.kaschani@uni-due.de
lab head
Farnusch Kaschani
contact affiliation	University Duisburg-Essen
contact email	farnusch.kaschani@uni-due.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/2025/02/PXD058896

PRIDE project URI

• PRIDE
  1. PXD058896
     1. Label: PRIDE project
     2. Name: Identification of Sulphostin targets unsig competitive ABPP