PXD073248-1

PXD073248 is an original dataset announced via ProteomeXchange.

Title	Degradation of G-Quadruplex Binding Proteins in Chromatin Using G4-Ligand-Based PROTACs
Description	Targeted protein degradation can intervene with the function of disease-related proteins, but most current approaches rely on direct ligand engagement of a protein target, limiting their applicability to proteins that are difficult to bind selectively. We present a conceptually unique approach to degrade proteins associated with DNA G-quadruplex (G4) secondary structures in a chromatin context. G4s are non-canonical nucleic acid structures that form at regulatory regions of transcriptionally active genes in open chromatin, and are abundant in cancer states. While many proteins recognize or regulate G4 structures, selectively targeting G4-binding proteins in their native chromatin environment is challenging. Our bifunctional molecules are PROTACs that bind naturally occurring G4s, recruit E3 ubiquitin ligases and degrade G4-specific transcription factors and chromatin remodelers such as FUS, SMARCA4, and ATRX. These proteins are important therapeutic targets that play crucial roles in transcription regulation and DNA repair. Our approach has the potential to be exploited in a therapeutic strategy to target diseases characterized by aberrant G4 activity, such as cancers.
HostingRepository	PRIDE
AnnounceDate	2026-01-27
AnnouncementXML	Submission_2026-01-27_05:13:33.396.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Samuel Lord
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-19 12:30:56	ID requested
⏵ 1	2026-01-27 05:13:33	announced

Dataset with its publication pending

submitter keyword: G‑quadruplex

G4L‑PROTACs

Chromatin

Targeted protein degradation

Shankar Balasubramanian
contact affiliation	Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK. Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK. School of Clinical Medicine, University of Cambridge, Cambridge, UK.
contact email	Shankar.Balasubramanian@cruk.cam.ac.uk
lab head
Samuel Lord
contact affiliation	Cancer Research UK Institute, Cambridge
contact email	sam.lord@cruk.cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD073248
     1. Label: PRIDE project
     2. Name: Degradation of G-Quadruplex Binding Proteins in Chromatin Using G4-Ligand-Based PROTACs