PXD035954 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Design and evaluation of a cyclobutane diazirine alkyne tag for photoaffinity labeling in cells |
Description | Alkyl diazirines are frequently used in photoaffinity labeling to trap and identify small molecule–protein interactions. How-ever, the alkyl diazirine can preferentially label acidic amino acids and acidic protein surfaces in a pH-dependent manner, presumably via a long-lived alkyl diazo intermediate. To alter this reactivity preference, we developed PALBOX, a novel cyclobutane diazirine photoaffinity tag with reduced pH-dependent reactivity. We show that PALBOX is readily derivatized and attached to small molecules to profile their binding interactions in cells. Systematic experiments with biological sub-strates show that the cyclobutane diazirine scaffold does not exhibit reactivity characteristic of unconstrained alkyl diazo in-termediates. Using a set of small molecule fragments and ligands, we show that photoaffinity probes equipped with PALBOX can label known protein targets in cells with higher specificity. Finally, we demonstrate that ligands equipped with PALBOX can accurately map small molecule–protein binding sites. Thus, PALBOX is a versatile diazirine-based pho-toaffinity tag for use in the development of chemical probes for photoaffinity labeling experiments, including the study of small molecule–protein interactions. |
HostingRepository | PRIDE |
AnnounceDate | 2024-01-04 |
AnnouncementXML | Submission_2024-01-04_04:03:09.787.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Christina Woo |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; carbamoylated residue; monohydroxylated residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-08-10 09:31:22 | ID requested | |
⏵ 1 | 2024-01-04 04:03:10 | announced | |
Publication List
West AV, Amako Y, Woo CM, Design and Evaluation of a Cyclobutane Diazirine Alkyne Tag for Photoaffinity Labeling in Cells. J Am Chem Soc, 144(46):21174-21183(2022) [pubmed] |
10.1021/jacs.2c08257; |
Keyword List
submitter keyword: cereblon, diazirine, thalidomide,photoaffinity labeling, binding site mapping |
Contact List
Christina M. Woo |
contact affiliation | Department of Chemistry and Chemical Biology, Harvard University, Cambridge MA, 02138 |
contact email | cwoo@chemistry.harvard.edu |
lab head | |
Christina Woo |
contact affiliation | Harvard University |
contact email | cwoo@chemistry.harvard.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035954
- Label: PRIDE project
- Name: Design and evaluation of a cyclobutane diazirine alkyne tag for photoaffinity labeling in cells