PXD059909

PXD059909 is an original dataset announced via ProteomeXchange.

Title	A Hydrophobic Photo-Uncaging Reaction to Profile Lipid Droplet Interactome in Tissues
Description	Most bioorthogonal photo-uncaging reactions preferentially occur in polar environments to accommodate biological applications in the aqueous cellular milieu. However, they are not precisely designed to chemically adapt to the diverse microenvironments of the cell. Herein, we report a hydrophobic photo-uncaging reaction with tailored photolytic kinetics towards solvent polarity. Structural modulations of the aminobenzoquinone-based photocage reveal the impact of cyclic ring size, steric substituent, and electronic substituent on the individual uncaging kinetics (kH2O & kdioxane) and polarity preference (kdioxane / kH2O). Rational incorporation of optimized moieties leads to up to 20.2-fold non-polar kinetic selectivity (kdioxane / kH2O). Further photochemical spectroscopic characterizations and theoretical calculations together uncover the mechanism underlying the polarity-dependent uncaging kinetics. The uncaged ortho-quinone methide product bears covalent reactivity towards diverse nucleophiles of a protein revealed by tandem mass spectrometry. Finally, we demonstrate the application of such lipophilic photo-uncaging chemistry towards selective labeling and profiling of proteins in proximity to lipid droplets (LDs) inside human fatty liver tissues. Together, this work studies the solvent polarity effects of a photo-uncaging reaction and chemically adapts it toward suborganelle-targeted protein proximity labeling and profiling.
HostingRepository	iProX
AnnounceDate	2025-01-17
AnnouncementXML	Submission_2025-01-16_19:28:45.775.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nan Zhao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-16 19:28:22	ID requested
⏵ 1	2025-01-16 19:28:46	announced

Dataset with its publication pending

submitter keyword: photocage, photo-uncaging, proximity labeling, quinone methide, lipid droplets.

Lihua Zhang
contact affiliation	Dalian Institute of Chemical Physics
contact email	lihuazhang@dicp.ac.cn
lab head
Nan Zhao
contact affiliation	Dalian Institute of Chemical Physics
contact email	zhaonan@dicp.ac.cn
dataset submitter

iProX dataset URI