PXD051902-1

PXD051902 is an original dataset announced via ProteomeXchange.

Title	Orthogonal Conjugation via Endoglycosidase and Microbial Transglutaminase Enables Efficient Synthesis of Dual-Payload Antibody-Drug Conjugates
Description	Antibody drug conjugates (ADCs) are a rapidly growing field of therapeutics which combines the highly specific targeting ability of an antibody with a cytotoxic drug to deliver the payload in a targeted manner to cancer cells. Traditional ADC construction used stochastic conjugation methods resulting in heterogeneous products with subpopulations having mixed stability and pharmacokinetics. Consequently, recent efforts have favored site-specific conjugation methods that produce homogeneous ADCs with improved therapeutic indexes. Here we report a highly efficient site-specific conjugation method that combines an endoglycosidase and microbial transglutaminase to construct homogeneous and well defined antibody drug conjugates. We found an Endo-S2 treated IgG antibody, which conserves the inner-most GlcNAc residue at the conserved N-glycosylation site, is an excellent substrate for mTG conjugation activity. We further demonstrate an Fc glycan remodeling strategy with Endo-S2 can be used for loading of a second payload to construct a dual-drug ADC.
HostingRepository	PRIDE
AnnounceDate	2026-05-29
AnnouncementXML	Submission_2026-05-28_19:57:05.469.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peter Nemes
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-30 12:35:40	ID requested
⏵ 1	2026-05-28 19:57:06	announced

10.1021/ACSCHEMBIO.6C00229;

submitter keyword: None

Peter Nemes
contact affiliation	Department of Chemistry & Biochemistry, University of Maryland at College Park
contact email	nemes@umd.edu
lab head
Peter Nemes
contact affiliation	University of Maryland, College Park
contact email	nemes@umd.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051902
     1. Label: PRIDE project
     2. Name: Orthogonal Conjugation via Endoglycosidase and Microbial Transglutaminase Enables Efficient Synthesis of Dual-Payload Antibody-Drug Conjugates