⮝ Full datasets listing
PXD068136-1
PXD068136 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | High Coverage and Quantitative Small Molecule Binding Site Discovery with Silyl Ether Enabled Quantitative Chemoproteomics |
| Description | Most therapeutics are small molecules that function by interacting with specific protein targets. Consequently, delineating the protein targets, including the specific binding sites, for chemical probes and clinical candidates is essential to ensure potent on-target activity and to minimize engagement of unfavorable off-targets. The pairing of mass spectrometry-based chemoproteomics with photoaffinity labeling (PAL) has emerged as a favored approach to generate proteome-wide target engagement maps for reversible compounds. However, a key limitation of most PAL-based proteomic platforms is the absence of strategies that report precise binding sites and enable direct head-to-head comparisons of relative target engagement at these sites by different lead compounds. This gap stems from a confluence of factors including the complex fragmentation patterns for crosslinked peptides, poor recovery of peptides crosslinked with large hydrophobic molecules, and modification masses that differ between molecules of interest (MOI). To address these challenges, here we establish the Silyl Ether Enables Chemoproteomic Interaction and Target Engagement (SEE-CITE) approach. SEE- CITE incorporates a fully functionalized chemically cleavable photocrosslinking handle that enables precise site-of-labeling identification and head-to-head comparisons of relative binding site engagement by chemically diverse compounds. To ensure high confidence localization of labeled residues, we also enabled enhanced mapping of photocrosslinked sites by extending the MSFragger algorithm of the FragPipe computational platform to report localization scores customized for PAL and SEE-CITE data. By benchmarking SEE-CITE using scout fragments and analogues of the FDA approved kinase inhibitors, dasatinib and asciminib, we identify known and novel binding sites, including for high impact targets, such as BCR-ABL1, RTN4, and COX5A. |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-12-30 |
| AnnouncementXML | Submission_2025-12-30_16:43:03.273.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Chau Ngo |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Biotin |
| Instrument | Orbitrap Eclipse |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-09-05 18:07:17 | ID requested | |
| ⏵ 1 | 2025-12-30 16:43:03 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: photocrosslinking, interactive, diazirine, silyl ether, chemoproteomics, DatasetType:Proteomics |
Contact List
| Keriann Backus, Ph.D. | |
|---|---|
| contact affiliation | UCLA |
| contact email | kbackus@mednet.ucla.edu |
| lab head | |
| Chau Ngo | |
| contact affiliation | University of California Los Angeles |
| contact email | chaudngo@g.ucla.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive-ftp.ucsd.edu/v10/MSV000099063/ |
