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
| Autor: | Castañeda, Lourdes, Maruani, Antoine, Schumacher, Felix F., Miranda, Enrique, Chudasama, Vijay, Chester, Kerry A., Baker, James R., Smith, Mark E. B., Caddick, Stephen |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Chemical Communications (Cambridge, England) |
| ISSN: | 1364-548X 1359-7345 |
| Popis: | Homogeneous antibody–drug conjugation is affected using a novel thiomaleamic acid linker that is stable at physiological temperature and pH, but quantitatively cleaves at lysosomal pH to release the drug payload. 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. |
| Databáze: | OpenAIRE |
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