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Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation

[Image: see text] Fusion proteins play an essential role in the biosciences but suffer from several key limitations, including the requirement for N-to-C terminal ligation, incompatibility of constituent domains, incorrect folding, and loss of biological activity. This perspective focuses on chemica...

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Autores principales: Taylor, Ross J., Geeson, Michael B., Journeaux, Toby, Bernardes, Gonçalo J. L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389620/
https://www.ncbi.nlm.nih.gov/pubmed/35912579
http://dx.doi.org/10.1021/jacs.2c00129
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author Taylor, Ross J.
Geeson, Michael B.
Journeaux, Toby
Bernardes, Gonçalo J. L.
author_facet Taylor, Ross J.
Geeson, Michael B.
Journeaux, Toby
Bernardes, Gonçalo J. L.
author_sort Taylor, Ross J.
collection PubMed
description [Image: see text] Fusion proteins play an essential role in the biosciences but suffer from several key limitations, including the requirement for N-to-C terminal ligation, incompatibility of constituent domains, incorrect folding, and loss of biological activity. This perspective focuses on chemical and enzymatic approaches for the post-translational generation of well-defined protein–protein conjugates, which overcome some of the limitations faced by traditional fusion techniques. Methods discussed range from chemical modification of nucleophilic canonical amino acid residues to incorporation of unnatural amino acid residues and a range of enzymatic methods, including sortase-mediated ligation. Through summarizing the progress in this rapidly growing field, the key successes and challenges associated with using chemical and enzymatic approaches are highlighted and areas requiring further development are discussed.
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spelling pubmed-93896202022-08-20 Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation Taylor, Ross J. Geeson, Michael B. Journeaux, Toby Bernardes, Gonçalo J. L. J Am Chem Soc [Image: see text] Fusion proteins play an essential role in the biosciences but suffer from several key limitations, including the requirement for N-to-C terminal ligation, incompatibility of constituent domains, incorrect folding, and loss of biological activity. This perspective focuses on chemical and enzymatic approaches for the post-translational generation of well-defined protein–protein conjugates, which overcome some of the limitations faced by traditional fusion techniques. Methods discussed range from chemical modification of nucleophilic canonical amino acid residues to incorporation of unnatural amino acid residues and a range of enzymatic methods, including sortase-mediated ligation. Through summarizing the progress in this rapidly growing field, the key successes and challenges associated with using chemical and enzymatic approaches are highlighted and areas requiring further development are discussed. American Chemical Society 2022-08-01 2022-08-17 /pmc/articles/PMC9389620/ /pubmed/35912579 http://dx.doi.org/10.1021/jacs.2c00129 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Taylor, Ross J.
Geeson, Michael B.
Journeaux, Toby
Bernardes, Gonçalo J. L.
Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation
title Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation
title_full Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation
title_fullStr Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation
title_full_unstemmed Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation
title_short Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation
title_sort chemical and enzymatic methods for post-translational protein–protein conjugation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389620/
https://www.ncbi.nlm.nih.gov/pubmed/35912579
http://dx.doi.org/10.1021/jacs.2c00129
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