Development of Triantennary N-Acetylgalactosamine Conjugates as Degraders for Extracellular Proteins
Yaxian Zhou, Peng Teng, Nathan T. Montgomery, Xiaolei Li, Weiping Tang
Abstract
-acetylgalactosamine (tri-GalNAc), was conjugated to biotin, antibodies, or fragments of antibodies to generate a new class of degraders. We demonstrated that the extracellular protein targets could be successfully internalized and delivered into lysosome for degradation in liver cell lines specifically by these degraders. This work will add a new dimension to TPD with cell type specificity.
Topics & Concepts
Asialoglycoprotein receptorLysosomeExtracellularBiochemistryProteolysisChemistryFusion proteinCell biologyMannose 6-phosphate receptorBiologyHepatocyteEnzymeIn vitroRecombinant DNAGeneProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysPeptidase Inhibition and Analysis