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Updated: May 9, 2026
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
Acid-cleavable thiomaleamic acid linker for homogeneous antibody-drug conjugation
Lourdes Castañeda1, Antoine Maruani, Felix F Schumacher
1Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK.
Abstract:
In this communication we describe a novel acid-cleavable linker strategy for antibody-drug conjugation. Functional disulfide bridging of the single interchain disulfide bond of a trastuzumab Fab fragment yields a homogeneous antibody-drug conjugate bearing a thiomaleamic acid linker. This linker is stable at physiological pH and temperature, but quantitatively cleaves at lysosomal pH to release the drug payload.
