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

作者:Castaneda Lourdes; Maruani Antoine; Schumacher Felix F; Miranda Enrique; Chudasama Vijay; Chester Kerry A; Baker James R; Smith Mark E B*; Caddick Stephen
来源:Chemical Communications, 2013, 49(74): 8187-8189.
DOI:10.1039/c3cc45220d

摘要

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.

  • 出版日期2013