PXD058896 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-12-16 01:18:42 | ID requested | |
⏵ 1 | 2025-02-24 23:35:58 | announced | |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD058896
- Label: PRIDE project
- Name: Identification of Sulphostin targets unsig competitive ABPP