PXD042243-1

PXD042243 is an original dataset announced via ProteomeXchange.

Title	Design of a mucin-selective protease for targeted degradation of cancer-associated mucins
Description	Targeted 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.
HostingRepository	PRIDE
AnnounceDate	2023-07-21
AnnouncementXML	Submission_2023-07-21_09:27:40.454.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	NicholasRiley
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	complex glycosylation
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-15 16:13:16	ID requested
⏵ 1	2023-07-21 09:27:40	announced
2	2023-11-14 06:39:26	announced	2023-11-14: Updated project metadata.

submitter keyword: mucins, glycoprotease,Targeted degradation, TAILS

Carolyn R.Bertozzi
contact affiliation	Department of Chemistry, Stanford University
contact email	bertozzi@stanford.edu
lab head
NicholasRiley
contact affiliation	Stanford University
contact email	riley.nicholasm@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042243
     1. Label: PRIDE project
     2. Name: Design of a mucin-selective protease for targeted degradation of cancer-associated mucins