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Acid-cleavable thiomaleamic acid linker for homogeneous antibody-drug conjugation.

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.

SUBMITTER: Castaneda L

PROVIDER: S-EPMC3763782 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Acid-cleavable thiomaleamic acid linker for homogeneous antibody-drug conjugation.

Castañeda Lourdes L Maruani Antoine A Schumacher Felix F FF Miranda Enrique E Chudasama Vijay V Chester Kerry A KA Baker James R JR Smith Mark E B ME Caddick Stephen S

Chemical communications (Cambridge, England) 20130901 74

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. ...[more]

PMID: 23929130

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