Disulfide re-bridging reagents for single-payload antibody-drug conjugates

Numerous antibody-drug conjugate (ADC) linker technologies exist for the synthesis of ADCs with drug-to-antibody ratios (DARs) being an even integer (typically 2, 4 or 8). However, ADCs with odd-integer DARs are significantly harder to synthesise. Here, we report the synthesis of ADCs loaded with a...

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Detalles Bibliográficos
Autores principales: King, Thomas A., Walsh, Stephen J., Kapun, Mia, Wharton, Thomas, Krajcovicova, Sona, Glossop, Melanie S., Spring, David R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10414422/
https://www.ncbi.nlm.nih.gov/pubmed/37492000
http://dx.doi.org/10.1039/d3cc02980h
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author King, Thomas A.
Walsh, Stephen J.
Kapun, Mia
Wharton, Thomas
Krajcovicova, Sona
Glossop, Melanie S.
Spring, David R.
author_facet King, Thomas A.
Walsh, Stephen J.
Kapun, Mia
Wharton, Thomas
Krajcovicova, Sona
Glossop, Melanie S.
Spring, David R.
author_sort King, Thomas A.
collection PubMed
description Numerous antibody-drug conjugate (ADC) linker technologies exist for the synthesis of ADCs with drug-to-antibody ratios (DARs) being an even integer (typically 2, 4 or 8). However, ADCs with odd-integer DARs are significantly harder to synthesise. Here, we report the synthesis of ADCs loaded with a single warhead, using TetraDVP linkers which simultaneously re-bridge all four interchain disulfides of an IgG1 antibody.
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spelling pubmed-104144222023-08-11 Disulfide re-bridging reagents for single-payload antibody-drug conjugates King, Thomas A. Walsh, Stephen J. Kapun, Mia Wharton, Thomas Krajcovicova, Sona Glossop, Melanie S. Spring, David R. Chem Commun (Camb) Chemistry Numerous antibody-drug conjugate (ADC) linker technologies exist for the synthesis of ADCs with drug-to-antibody ratios (DARs) being an even integer (typically 2, 4 or 8). However, ADCs with odd-integer DARs are significantly harder to synthesise. Here, we report the synthesis of ADCs loaded with a single warhead, using TetraDVP linkers which simultaneously re-bridge all four interchain disulfides of an IgG1 antibody. The Royal Society of Chemistry 2023-07-18 /pmc/articles/PMC10414422/ /pubmed/37492000 http://dx.doi.org/10.1039/d3cc02980h Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
King, Thomas A.
Walsh, Stephen J.
Kapun, Mia
Wharton, Thomas
Krajcovicova, Sona
Glossop, Melanie S.
Spring, David R.
Disulfide re-bridging reagents for single-payload antibody-drug conjugates
title Disulfide re-bridging reagents for single-payload antibody-drug conjugates
title_full Disulfide re-bridging reagents for single-payload antibody-drug conjugates
title_fullStr Disulfide re-bridging reagents for single-payload antibody-drug conjugates
title_full_unstemmed Disulfide re-bridging reagents for single-payload antibody-drug conjugates
title_short Disulfide re-bridging reagents for single-payload antibody-drug conjugates
title_sort disulfide re-bridging reagents for single-payload antibody-drug conjugates
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10414422/
https://www.ncbi.nlm.nih.gov/pubmed/37492000
http://dx.doi.org/10.1039/d3cc02980h
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