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

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...

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Autores principales: Castañeda, Lourdes, Maruani, Antoine, Schumacher, Felix F., Miranda, Enrique, Chudasama, Vijay, Chester, Kerry A., Baker, James R., Smith, Mark E. B., Caddick, Stephen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2013
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763782/
https://www.ncbi.nlm.nih.gov/pubmed/23929130
http://dx.doi.org/10.1039/c3cc45220d
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author Castañeda, Lourdes
Maruani, Antoine
Schumacher, Felix F.
Miranda, Enrique
Chudasama, Vijay
Chester, Kerry A.
Baker, James R.
Smith, Mark E. B.
Caddick, Stephen
author_facet Castañeda, Lourdes
Maruani, Antoine
Schumacher, Felix F.
Miranda, Enrique
Chudasama, Vijay
Chester, Kerry A.
Baker, James R.
Smith, Mark E. B.
Caddick, Stephen
author_sort Castañeda, Lourdes
collection PubMed
description 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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spelling pubmed-37637822013-09-05 Acid-cleavable thiomaleamic acid linker for homogeneous antibody–drug conjugation Castañeda, Lourdes Maruani, Antoine Schumacher, Felix F. Miranda, Enrique Chudasama, Vijay Chester, Kerry A. Baker, James R. Smith, Mark E. B. Caddick, Stephen Chem Commun (Camb) Chemistry 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. Royal Society of Chemistry 2013-06-21 2013-08-09 /pmc/articles/PMC3763782/ /pubmed/23929130 http://dx.doi.org/10.1039/c3cc45220d Text en This journal is © The Royal Society of Chemistry 2013 http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemistry
Castañeda, Lourdes
Maruani, Antoine
Schumacher, Felix F.
Miranda, Enrique
Chudasama, Vijay
Chester, Kerry A.
Baker, James R.
Smith, Mark E. B.
Caddick, Stephen
Acid-cleavable thiomaleamic acid linker for homogeneous antibody–drug conjugation
title Acid-cleavable thiomaleamic acid linker for homogeneous antibody–drug conjugation
title_full Acid-cleavable thiomaleamic acid linker for homogeneous antibody–drug conjugation
title_fullStr Acid-cleavable thiomaleamic acid linker for homogeneous antibody–drug conjugation
title_full_unstemmed Acid-cleavable thiomaleamic acid linker for homogeneous antibody–drug conjugation
title_short Acid-cleavable thiomaleamic acid linker for homogeneous antibody–drug conjugation
title_sort acid-cleavable thiomaleamic acid linker for homogeneous antibody–drug conjugation
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763782/
https://www.ncbi.nlm.nih.gov/pubmed/23929130
http://dx.doi.org/10.1039/c3cc45220d
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