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PXD042243-1

PXD042243 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDesign of a mucin-selective protease for targeted degradation of cancer-associated mucins
DescriptionTargeted protein degradation is an emerging strategy for the elimination of classically undruggable proteins. Here, to expand the landscape of targetable substrates, we designed degraders that achieve substrate selectivity via recognition of a discrete peptide- and glycan- motif and achieve cell-type selectivity via antigen-driven cell surface binding. We applied this approach to mucins, O-glycosylated proteins that drive cancer progression through biophysical and immunological mechanisms. Engineering of a bacterial mucin-selective protease yielded a variant for fusion to a cancer antigen-binding nanobody. The resulting conjugate selectively degraded mucins on cancer cells, promoted cell death in culture models of mucin-driven growth and survival, and reduced tumor growth in murine models of breast cancer progression. This work establishes a blueprint for the development of biologics that degrade specific glycoproteins on target cells.
HostingRepositoryPRIDE
AnnounceDate2023-07-21
AnnouncementXMLSubmission_2023-07-21_09:27:40.454.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterNicholasRiley
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListcomplex glycosylation
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-05-15 16:13:16ID requested
12023-07-21 09:27:40announced
22023-11-14 06:39:26announced2023-11-14: Updated project metadata.
Publication List
Keyword List
submitter keyword: mucins, glycoprotease,Targeted degradation, TAILS
Contact List
Carolyn R.Bertozzi
contact affiliationDepartment of Chemistry, Stanford University
contact emailbertozzi@stanford.edu
lab head
NicholasRiley
contact affiliationStanford University
contact emailriley.nicholasm@gmail.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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