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Castañeda, Lourdes; Maruani, Antoine; Schumacher, Felix F; Miranda, Enrique; Chudasama, Vijay; Chester, Kerry A; Baker, James R; Smith, Mark E B; Caddick, Stephen
Chemical communications (Cambridge, England), 01/2013, Volume: 49, Issue: 74Journal Article
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.
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