A dual-enzyme cleavable linker for antibody-drug conjugates.

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.

Authors:

JD Bargh, SJ Walsh, N Ashman, A Isidro-Llobet, JS Carroll, DR Spring

Journal:

Chem Commun (Camb)

Citation info:

57(28):3457-3460

Publication date:

11th Apr 2021

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