PXD079357 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Sulfonyl-Imidazopyridines Decouple Reactivity from Stability for Ligandability Mapping and Covalent Inhibitor Discovery |
| Description | Covalent probes and therapeutics require a balance between sufficient reactivity toward protein sites and stability for function in biological systems, yet enhancing stability often attenuates electrophilicity, constraining ligand discovery. Here, we show that single-atom N-to-C substitutions of sulfonyl-purines at the nucleofuge position decouples reactivity from stability. Systematic chemical proteomic profiling identifies sulfonyl-imidazopyridines as a class of electrophiles with enhanced cellular and in vivo stability while retaining tunable reactivity toward functional tyrosine and lysine sites. These electrophiles expand access to proteomic sites not engaged by parent sulfonyl-purines or related -triazoles. Importantly, the differential binding of N7- vs N9-sulfonyl-imidazopyridine regioisomer pairs expedites the discovery of proteome wide-selective inhibitors of metabolic targets, including LSS, PGAM1, and DCTPP1. Collectively, this work establishes a general strategy for stabilizing electrophiles and introduces a platform for global ligandability mapping guided by regioselective recognition. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-08-21 |
| AnnouncementXML | Submission_2026-08-21_06:37:31.437.xml |
| DigitalObjectIdentifier | https://doi.org/10.6019/PXD079357 |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Ku-Lung Hsu |
| SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Orbitrap Exploris 480 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2026-06-07 20:39:07 | ID requested | |
| ⏵ 1 | 2026-08-21 06:37:31 | announced | |
Publication List
Keyword List
| submitter keyword: chemoproteomics |
Contact List
| Ku-Lung Hsu |
|---|
| contact affiliation | The University of Texas at Austin |
| contact email | ken.hsu@austin.utexas.edu |
| lab head | |
| Ku-Lung Hsu |
|---|
| contact affiliation | The University of Texas at Austin |
| contact email | ken.hsu@austin.utexas.edu |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD079357
- Label: PRIDE project
- Name: Sulfonyl-Imidazopyridines Decouple Reactivity from Stability for Ligandability Mapping and Covalent Inhibitor Discovery
