ArticleACS chemical biology2022
Site-Specific Chemoenzymatic Conjugation of High-Affinity M6P Glycan Ligands to Antibodies for Targeted Protein Degradation.
Article in ACS chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Unlocking the "undruggable": current landscape and emerging frontiers in lysosomal receptor-mediated protein degradation.Drug delivery · 2026Review
- Using Synthetic Glycans to Investigate Anti-Glycan Antibodies and Explore Their Medical Potential.Angewandte Chemie (International ed. in English) · 2026Review
- Targeted Lysosomal Degradation of Extracellular and Membrane Proteins: From Receptor Hijacking to Programmable Endolysosomal Routing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Orthogonal Conjugation via Endoglycosidase and Microbial Transglutaminase Enables Efficient Synthesis of Dual-Payload Antibody-Drug Conjugates.ACS chemical biology · 2026Article
- Article
- Targeted degradation of extracellular proteins: state of the art and diversity of degrader designs.Journal of hematology & oncology · 2025Review
- Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics.Chemical reviews · 2025Review
- Recent Advances in Synthetic Strategies of Glycans and their Pharmaceutical Applications.Current medicinal chemistry · 2025Review
- Directed evolution of genetically encoded LYTACs for cell-mediated delivery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Targeting EGFR with molecular degraders as a promising strategy to overcome resistance to EGFR inhibitors.Future medicinal chemistry · 2024Review
- Directed Evolution of Genetically Encoded LYTACs for Cell-Mediated Delivery.bioRxiv : the preprint server for biology · 2023Article
- IGF2 Peptide-Based LYTACs for Targeted Degradation of Extracellular and Transmembrane Proteins.Molecules (Basel, Switzerland) · 2023Article
- Targeted degradation of extracellular secreted and membrane proteins.Trends in pharmacological sciences · 2023Review
- Synthetic Site-Specific Antibody-Ligand Conjugates Promote Asialoglycoprotein Receptor-Mediated Degradation of Extracellular Human PCSK9.ACS chemical biology · 2023Article
- Development of Oligomeric Mannose-6-phosphonate Conjugates for Targeted Protein Degradation.ACS medicinal chemistry letters · 2023Article
- Glycomimetics for the inhibition and modulation of lectins.Chemical Society reviews · 2023Review
- Site-Specific Antibody Conjugation with Payloads beyond Cytotoxins.Molecules (Basel, Switzerland) · 2023Review
- Site-selective sulfation of N-glycans by human GlcNAc-6-O-sulfotransferase 1 (CHST2) and chemoenzymatic synthesis of sulfated antibody glycoforms.Bioorganic chemistry · 2022Article
- Article
- Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update for 2021-2022.Mass spectrometry reviewsReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Lysosome-targeting chimeras (LYTACs) offer an opportunity for the degradation of extracellular and membrane-associated proteins of interest. Here, we report an efficient chemoenzymatic method that enables a single-step and site-specific conjugation of high-affinity mannose-6-phosphate (M6P) glycan ligands to antibodies without the need of protein engineering and conventional click reactions that would introduce "unnatural" moieties, yielding homogeneous antibody-M6P glycan conjugates for targeted degradation of membrane-associated proteins. Using trastuzumab and cetuximab as model antibodies, we showed that the wild-type endoglycosidase S (Endo-S) could efficiently perform the antibody deglycosylation and simultaneous transfer of an M6P-glycan from a synthetic M6P-glycan oxazoline to the deglycosylated antibody in a one-pot manner, giving structurally well-defined antibody-M6P glycan conjugates. A two-step procedure, using wild-type Endo-S2 for deglycosylation followed by transglycosylation with an Endo-S2 mutant (D184M), was also efficient to provide M6P glycan-antibody conjugates. The chemoenzymatic approach was highly specific for Fc glycan remodeling when both Fc and Fab domains were glycosylated, as exemplified by the selective Fc-glycan remodeling of cetuximab. SPR binding analysis indicated that the M6P conjugates possessed a nanomolar range of binding affinities for the cation-independent mannose-6-phosphate receptor (CI-MPR). Preliminary cell-based assays showed that the M6P-trastuzumab and M6P-cetuximab conjugates were able to selectively degrade the membrane-associated HER2 and EGFR, respectively. This modular glycan-remodeling strategy is expected to find wide applications for antibody-based lysosome-targeted degradation of extracellular and membrane proteins.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.