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

• DOI: 10.1021/acschembio.3c00229
• Publication Date: 2023-06-27T17:21:45Z
• Authors: Thomas C. Donahue; Chong Ou; Qiang Yang; Robin Flinko; Xiao Zhang; Guanghui Zong; George K. Lewis; Lai-Xi Wang
• Keywords: Asialoglycoprotein receptor; PCSK9; Degradation

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) particularly attractive leveraged targeted protein (TPD). However, efficiency different glycan ligands ASGPR-mediated lysosomal delivery remains to be further characterized. In this study, we applied chemoenzymatic Fc remodeling method construct an array site-specific antibody-ligand conjugates carrying natural bi- and tri-antennary