Synthetic Site-Specific Antibody-Ligand Conjugates Promote Asialoglycoprotein Receptor-Mediated Degradation of Extracellular Human PCSK9.


Journal

ACS chemical biology
ISSN: 1554-8937
Titre abrégé: ACS Chem Biol
Pays: United States
ID NLM: 101282906

Informations de publication

Date de publication:
21 07 2023
Historique:
pmc-release: 21 07 2024
medline: 24 7 2023
pubmed: 27 6 2023
entrez: 27 6 2023
Statut: ppublish

Résumé

Targeted degradation using cell-specific lysosome targeting receptors is emerging as a new therapeutic strategy for the elimination of disease-associated proteins. The liver-specific human asialoglycoprotein receptor (ASGPR) is a particularly attractive lysosome targeting receptor leveraged for targeted protein degradation (TPD). However, the efficiency of different glycan ligands for ASGPR-mediated lysosomal delivery remains to be further characterized. In this study, we applied a chemoenzymatic Fc glycan remodeling method to construct an array of site-specific antibody-ligand conjugates carrying natural bi- and tri-antennary

Identifiants

pubmed: 37368876
doi: 10.1021/acschembio.3c00229
pmc: PMC10530246
mid: NIHMS1916104
doi:

Substances chimiques

Asialoglycoprotein Receptor 0
Ligands 0
Serine Endopeptidases EC 3.4.21.-
Proprotein Convertases EC 3.4.21.-
Asialoglycoproteins 0
Cetuximab PQX0D8J21J
Cholesterol, LDL 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1611-1623

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI155716
Pays : United States

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Auteurs

Thomas C Donahue (TC)

Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States.

Chong Ou (C)

Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States.

Qiang Yang (Q)

Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States.

Robin Flinko (R)

Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland 21201, United States.

Xiao Zhang (X)

Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States.

Guanghui Zong (G)

Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States.

George K Lewis (GK)

Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland 21201, United States.

Lai-Xi Wang (LX)

Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States.

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Classifications MeSH