PXD045992

PXD045992 is an original dataset announced via ProteomeXchange.

Title	Profiling the interactome of oligonucleotide drugs by proximity biotinylation
Description	Drug-ID applies proximity biotinylation to identify drug-protein interactions inside living cells. The covalent conjugation of a drug molecule with a biotin ligase enables targeted biotinylation of the drug-bound proteome and its identification by SILAC-MS/MS. We investigate the interactome of two well-known small molecule drugs, JQ1 and SAHA, and applied it for the identification of the interactome of RNaseH-recruiting antisense oligonucleotides (ASO). Drug-ID allows to de novo profile the drug-protein interactome under native conditions, directly inside living cells and at the pharmacologically effective concentration of the drug using minimal amount of input material. We apply the technology to study the dose-dependent aggregation of ASOs and the effect of different wing chemistries (LNA, Fluoro, MOE) and ASO lengths on the ASO-protein interactome. Finally, we demonstrate the detection of stress-induced interactome changes (Actinomycin D treatment) in living cells. Particularly broadly applicable in the field of oligonucleotide therapeutics is the in situ variant of the approach, which uses a recombinant biotin ligase and does not require genetic manipulation of the target cell.
HostingRepository	PRIDE
AnnounceDate	2024-01-11
AnnouncementXML	Submission_2024-01-11_02:54:14.547.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mirita Franz-Wachtel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-09 05:56:41	ID requested
1	2024-01-09 05:32:30	announced
⏵ 2	2024-01-11 02:54:14	announced	2024-01-11: Updated project metadata.

Dataset with its publication pending

submitter keyword: antisense oligonucleotide, BASU,Proximity biotinylation, drug protein interactome, live cell, biotin ligase, HDAC inhibitors, SILAC, in situ biotinylation, BET inhibitors, BioID

Thorsten Stafforst
contact affiliation	Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany
contact email	Thorsten.stafforst@uni-tuebingen.de
lab head
Mirita Franz-Wachtel
contact affiliation	Proteome Center Tuebingen
contact email	mirita.franz@uni-tuebingen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045992
     1. Label: PRIDE project
     2. Name: Profiling the interactome of oligonucleotide drugs by proximity biotinylation