Targeted protein degradation through site-specific antibody conjugation with mannose 6-phosphate glycan.

ABSTRACT: Recent developments in targeted protein degradation have provided great opportunities to eliminating extracellular protein targets using potential therapies with unique mechanisms of action and pharmacology. Among them, Lysosome-Targeting Chimeras (LYTACs) acting through mannose 6-phosphate receptor (M6PR) have been shown to facilitate degradation of several soluble and membrane-associated proteins in lysosomes with high efficiency. Herein we have developed a novel site-specific antibody conjugation approach to generate antibody mannose 6-phosphate (M6P) conjugates. The method uses a high affinity synthetic M6P glycan, bisM6P, that is coupled to an Fc-engineered antibody NNAS. This mutant without any effector function was generated by switching the native glycosylation site from position 2

SUBMITTER: Mukai K 

PROVIDER: S-EPMC11497922 | biostudies-literature | 2024 Jan-Dec

REPOSITORIES: biostudies-literature