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Updated: Nov 14, 2025

Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
Published on: September 14, 2018
A dual-enzyme cleavable linker for antibody-drug conjugates
Jonathan D Bargh1, Stephen J Walsh, Nicola Ashman
1Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. spring@ch.cam.ac.uk.
None:
A novel enzyme cleavable linker for antibody-drug conjugates is reported. The 3-O-sulfo-β-galactose linker is cleaved sequentially by two lysosomal enzymes - arylsulfatase A and β-galactosidase - to release the payload in targeted cells. An α-HER2 antibody-drug conjugate synthesised using this highly hydrophilic dual-cleavable linker exhibited excellent cytotoxicity and selectivity.
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