Acid-cleavable thiomaleamic acid linker for homogeneous antibody–drug conjugation† †Electronic supplementary information (ESI) available: 1H and 13C spectra for all novel compounds, and ES-MS spectra for all reactions with proteins described herein. See DOI: 10.1039/c3cc45220dClick here for additional data file.

نویسندگان

  • Lourdes Castañeda
  • Antoine Maruani
  • Felix F. Schumacher
  • Enrique Miranda
  • Vijay Chudasama
  • Kerry A. Chester
  • James R. Baker
  • Mark E. B. Smith
  • Stephen Caddick
چکیده

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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عنوان ژورنال:

دوره 49  شماره 

صفحات  -

تاریخ انتشار 2013