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PXD035924-1

PXD035924 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSelective Macrocyclic Peptide Modulators of Lys63-linked Ubiquitin Chains Disrupt DNA Damage Repair
DescriptionDeveloping an effective binder for a specific ubiquitin (Ub) chain is a promising approach for modulating various biological processes with potential applications in drug discovery. In this study, we combined the Random Non-standard Peptides Integrated Discovery (RaPID) method and chemical protein synthesis to screen an extended library of macrocyclic peptides against synthetic Lys63-linked Di-Ub. This enabled us to discover a novel binder with low nanomolar affinity and specificity for this particular Ub chain. We further chemically modified the most effective binder to generate next-generation binders. We show that our potent cyclic peptide is cell-permeable and inhibits DNA damage repair, leading to cell cycle arrest and apoptotic cell death. Concordantly, a pulldown experiment with the biotinylated analog of our lead cyclic peptide identified various proteins involved in DNA synthesis and damage repair. Collectively, we established a novel and powerful strategy for selective inhibition of protein-protein interactions associated with Lys63-linked Di-Ub using cyclic peptides. This study offers an advancement in modulating central Ub pathways and provides new opportunities in drug discovery areas associated with Ub signaling.
HostingRepositoryPRIDE
AnnounceDate2022-09-19
AnnouncementXMLSubmission_2022-09-18_23:33:09.126.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKeren Bendalak
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-08-10 08:02:08ID requested
12022-09-18 23:33:09announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Ubiquitin, DNA Damage Repair
Contact List
Ashraf Brik
contact affiliationFaculty of Biology, Technion - Israel institute of technology
contact emailabrik@technion.ac.il
lab head
Keren Bendalak
contact affiliationTechnion
contact emailkerenb@technion.ac.il
dataset submitter
Full Dataset Link List
Dataset FTP location
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