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PXD058896

PXD058896 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIdentification of Sulphostin targets unsig competitive ABPP
DescriptionCovalent 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.
HostingRepositoryPRIDE
AnnounceDate2025-02-25
AnnouncementXMLSubmission_2025-02-24_23:35:57.734.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFarnusch Kaschani
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos; LTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-12-16 01:18:42ID requested
12025-02-24 23:35:58announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: inhibitor development, natural product, dipeptidyl peptidase,Activity-based protein profiling, target identification
Contact List
Farnusch Kaschani
contact affiliationAnalytics Core Facility Essen (ACE), Chemische Biologie, Universität Duisburg-Essen, ZMB, Germany
contact emailfarnusch.kaschani@uni-due.de
lab head
Farnusch Kaschani
contact affiliationUniversity Duisburg-Essen
contact emailfarnusch.kaschani@uni-due.de
dataset submitter
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Dataset FTP location
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PRIDE project URI
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