PXD035924 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Selective Macrocyclic Peptide Modulators of Lys63-linked Ubiquitin Chains Disrupt DNA Damage Repair |
Description | Developing 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. |
HostingRepository | PRIDE |
AnnounceDate | 2022-09-19 |
AnnouncementXML | Submission_2022-09-18_23:33:09.126.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Keren Bendalak |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-08-10 08:02:08 | ID requested | |
⏵ 1 | 2022-09-18 23:33:09 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Ubiquitin, DNA Damage Repair |
Contact List
Ashraf Brik |
contact affiliation | Faculty of Biology, Technion - Israel institute of technology |
contact email | abrik@technion.ac.il |
lab head | |
Keren Bendalak |
contact affiliation | Technion |
contact email | kerenb@technion.ac.il |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035924
- Label: PRIDE project
- Name: Selective Macrocyclic Peptide Modulators of Lys63-linked Ubiquitin Chains Disrupt DNA Damage Repair