Self-assembled PROTACs enable glycoproteins degradation in the living cells.

ABSTRACT: We report here a two-component proteolysis targeting chimeras (PROTACs) strategy selectively targeting O-GalNAcylated and O-GlcNAcylated proteins for proteasomal degradation, which leads to severe toxicity in human cancer cell lines through perturbation of critical metabolic and signaling pathways governed by glycoproteins. Our approach termed as GlyTAC leverages from metabolic incorporation of easily accessible and cell-permeable peracetylated N-acetylglucosamine (GlcNAc) or N-acetylgalactosamine (GalNAc) analogues bearing an azido group into glycoproteins. In the living cells, the azido-modified glycoproteins serve as covalent anchors for the introduction of thalidomide moiety by strain-promoted azide-alkyne cycloaddition (SPAAC) to recruit E3 ligase cereblon

SUBMITTER: Chen H 

PROVIDER: S-EPMC11976659 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature