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Site-Specific Antibody Conjugation with Payloads beyond Cytotoxins

As antibody–drug conjugates have become a very important modality for cancer therapy, many site-specific conjugation approaches have been developed for generating homogenous molecules. The selective antibody coupling is achieved through antibody engineering by introducing specific amino acid or unna...

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Autor principal: Zhou, Qun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9921355/
https://www.ncbi.nlm.nih.gov/pubmed/36770585
http://dx.doi.org/10.3390/molecules28030917
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author Zhou, Qun
author_facet Zhou, Qun
author_sort Zhou, Qun
collection PubMed
description As antibody–drug conjugates have become a very important modality for cancer therapy, many site-specific conjugation approaches have been developed for generating homogenous molecules. The selective antibody coupling is achieved through antibody engineering by introducing specific amino acid or unnatural amino acid residues, peptides, and glycans. In addition to the use of synthetic cytotoxins, these novel methods have been applied for the conjugation of other payloads, including non-cytotoxic compounds, proteins/peptides, glycans, lipids, and nucleic acids. The non-cytotoxic compounds include polyethylene glycol, antibiotics, protein degraders (PROTAC and LYTAC), immunomodulating agents, enzyme inhibitors and protein ligands. Different small proteins or peptides have been selectively conjugated through unnatural amino acid using click chemistry, engineered C-terminal formylglycine for oxime or click chemistry, or specific ligation or transpeptidation with or without enzymes. Although the antibody protamine peptide fusions have been extensively used for siRNA coupling during early studies, direct conjugations through engineered cysteine or lysine residues have been demonstrated later. These site-specific antibody conjugates containing these payloads other than cytotoxic compounds can be used in proof-of-concept studies and in developing new therapeutics for unmet medical needs.
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spelling pubmed-99213552023-02-12 Site-Specific Antibody Conjugation with Payloads beyond Cytotoxins Zhou, Qun Molecules Review As antibody–drug conjugates have become a very important modality for cancer therapy, many site-specific conjugation approaches have been developed for generating homogenous molecules. The selective antibody coupling is achieved through antibody engineering by introducing specific amino acid or unnatural amino acid residues, peptides, and glycans. In addition to the use of synthetic cytotoxins, these novel methods have been applied for the conjugation of other payloads, including non-cytotoxic compounds, proteins/peptides, glycans, lipids, and nucleic acids. The non-cytotoxic compounds include polyethylene glycol, antibiotics, protein degraders (PROTAC and LYTAC), immunomodulating agents, enzyme inhibitors and protein ligands. Different small proteins or peptides have been selectively conjugated through unnatural amino acid using click chemistry, engineered C-terminal formylglycine for oxime or click chemistry, or specific ligation or transpeptidation with or without enzymes. Although the antibody protamine peptide fusions have been extensively used for siRNA coupling during early studies, direct conjugations through engineered cysteine or lysine residues have been demonstrated later. These site-specific antibody conjugates containing these payloads other than cytotoxic compounds can be used in proof-of-concept studies and in developing new therapeutics for unmet medical needs. MDPI 2023-01-17 /pmc/articles/PMC9921355/ /pubmed/36770585 http://dx.doi.org/10.3390/molecules28030917 Text en © 2023 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Zhou, Qun
Site-Specific Antibody Conjugation with Payloads beyond Cytotoxins
title Site-Specific Antibody Conjugation with Payloads beyond Cytotoxins
title_full Site-Specific Antibody Conjugation with Payloads beyond Cytotoxins
title_fullStr Site-Specific Antibody Conjugation with Payloads beyond Cytotoxins
title_full_unstemmed Site-Specific Antibody Conjugation with Payloads beyond Cytotoxins
title_short Site-Specific Antibody Conjugation with Payloads beyond Cytotoxins
title_sort site-specific antibody conjugation with payloads beyond cytotoxins
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9921355/
https://www.ncbi.nlm.nih.gov/pubmed/36770585
http://dx.doi.org/10.3390/molecules28030917
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