PXD052692

PXD052692 is an original dataset announced via ProteomeXchange.

Title	Chemical tools to expand the ligandable proteome: elaborated fragment-based photoreactive stereoprobes
Description	Efforts to expand the ligandable proteome have explored stereochemically defined fragments equipped with photoreactive and clickable handles (photo-stereoprobes) for mapping reversible small molecule-protein interactions in living systems. Here, we investigate the impact of structural elaboration of fragment photo-stereoprobes on interactions with the proteome of human cancer cells. We find that even conservative increases in size and complexity have profound effects on protein binding for fragment photo-stereoprobes, leading to enhanced stereoselective protein interactions, while abrogating others. We use stereochemically matched competitor ligands to assess the extent of protein binding in human cells, leading to the discovery of high-stoichiometry ligands for proteins from different functional classes, including a structurally novel set of epoxide hydrolase inhibitors. Our findings support the broad ligandability potential of the human proteome while also highlighting challenges in converting reversible small molecule-protein interaction maps into more advanced chemical probes.
HostingRepository	PRIDE
AnnounceDate	2024-05-31
AnnouncementXML	Submission_2024-05-31_09:48:45.554.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Natalia Milosevich
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-29 19:30:00	ID requested
⏵ 1	2024-05-31 09:48:45	announced

Dataset with its publication pending

submitter keyword: proteomics, chemical biology

Dr Benjamin
contact affiliation	Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
contact email	cravatt@scripps.edu
lab head
Natalia Milosevich
contact affiliation	Scripps Research
contact email	nmilosevich@scripps.edu
dataset submitter

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://ftp.pride.ebi.ac.uk/pride/data/archive/2024/05/PXD052692

PRIDE project URI

• PRIDE
  1. PXD052692
     1. Label: PRIDE project
     2. Name: Chemical tools to expand the ligandable proteome: elaborated fragment-based photoreactive stereoprobes