PXD054470 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Thioamide-warheads with enhanced cysteine reactivity and specificity for targeted covalent inhibitors |
| Description | Targeted covalent inhibitors (TCIs) form covalent bond with their target that requires tailored reactive functionalities identified as warheads. Here we present a versatile approach changing carboxamide functions with thioamides that transforms known warheads to softer electrophiles enhancing reactivity and specificity for covalent cysteine modification. Furthermore, the oxygen-sulfur (O-S) exchange led to the discovery of new electrophilic warhead chemotypes such as chloroethanethioamides and fluoroethanethioamides. The improved reactivity and specificity of thioamide warheads were demonstrated in comparative labelling experiments of carboxamide and thioamide ibrutinib analogues at BTK. Additionally, we synthesized and evaluated alkyne-tagged thioamide derivatives in chemoproteomic applications. In addition to the increased reactivity observed at the proteome level, the chloroethanethioamide probe preferentially labeled a different subset of the proteome compared to iodoacetamide. Our findings suggest that thioamide warheads are suitable for TCI development and chemical biology applications, offering alternative cysteine-specific chemotypes for future covalent probe design. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-09-07 |
| AnnouncementXML | Submission_2026-09-06_16:31:51.631.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Ronen Gabizon |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
| Instrument | Orbitrap Exploris 240 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2024-07-31 21:16:01 | ID requested | |
| ⏵ 1 | 2026-09-06 16:31:52 | announced | |
Publication List
| 10.1038/s41467-026-72993-6; |
| Petri L, Gabizon R, P, é, czka N, Á, br, á, nyi-Balogh P, Simon J, Imre T, Ferenczy GG, London N, Keser, ű GM, -Halothioamide warheads with enhanced cysteine reactivity and specificity for covalent protein labelling. Nat Commun, 17(1):(2026) [pubmed] |
Keyword List
| submitter keyword: warhead, proteomics,cystein, covalent inhibitors |
Contact List
| Nir London |
|---|
| contact affiliation | Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel |
| contact email | nir.london@weizmann.ac.il |
| lab head | |
| Ronen Gabizon |
|---|
| contact affiliation | Department of Chemical and Structural Biology, Weizmann Institute of Science |
| contact email | ronen.gabizon@weizmann.ac.il |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD054470
- Label: PRIDE project
- Name: Thioamide-warheads with enhanced cysteine reactivity and specificity for targeted covalent inhibitors
