PXD035954

PXD035954 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-10 09:31:22	ID requested
⏵ 1	2024-01-04 04:03:10	announced

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;

submitter keyword: cereblon, diazirine, thalidomide,photoaffinity labeling, binding site mapping

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

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PRIDE project URI

• PRIDE
  1. PXD035954
     1. Label: PRIDE project
     2. Name: Design and evaluation of a cyclobutane diazirine alkyne tag for photoaffinity labeling in cells