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- W2977463336 abstract "Temporal and reversible control over protein and cell conjugations holds great potential for traceless release of antibody–drug conjugates (ADCs) on tumor sites as well as on-demand altering or removal of targeting elements on cell surface. We herein developed a bioorthogonal and traceless releasable reaction on proteins and intact cells to fulfill such purposes. A systematic survey of transition metals in catalyzing the bioorthogonal cleavage reactions revealed that copper complexes such as Cu(I)-BTTAA and dual-substituted propargyl (dsPra) or propargyloxycarbonyl (dsProc) moieties offered a bioorthogonal releasable pair for reversible blockage and rescue of primary amines and phenol alcohols on small molecule drugs, protein side chains, as well as intact cell surface. For proof-of-concept, we employed such Cu(I)-BTTAA/dsProc and Cu(I)-BTTAA/dsPra pairs as a “traceless linker” strategy to construct cleavable ADCs to unleash cytotoxic compounds on cancer cells in situ and as a “reversible modification” strategy for cell surface engineering. Furthermore, by coupling with the genetic code expansion strategy, we site-specifically modulated ligand–receptor interactions on live cell membranes. Together, our work expanded the transition-metal-mediated bioorthogonal cleavage tool kit from terminal decaging to internal-linker breakage, which offered a temporal and reversible conjugation strategy on therapeutic proteins and cells." @default.
- W2977463336 created "2019-10-10" @default.
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- W2977463336 date "2019-10-03" @default.
- W2977463336 modified "2023-10-15" @default.
- W2977463336 title "Copper-Triggered Bioorthogonal Cleavage Reactions for Reversible Protein and Cell Surface Modifications" @default.
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- W2977463336 doi "https://doi.org/10.1021/jacs.9b05833" @default.
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