A dual-enzyme cleavable linker for antibody–drug conjugates. Issue 28 (9th March 2021)

• Record Type: Journal Article
• Authors: Bargh, Jonathan D.; Walsh, Stephen J.; Ashman, Nicola; Isidro-Llobet, Albert; Carroll, Jason S.; Spring, David R.
• Is Part Of: Chemical communications. Volume 57:Issue 28(2021)
• Page Start: 3457
• Page End: 3460
• Publication Date: 2021-03-09
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d1cc00957e
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : A 3- O -sulfo-β-galactose linker is cleaved by two lysosomal enzymes to release payloads from ADCs at targeted cancer cells. Abstract : 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.