An overview of chemo- and site-selectivity aspects in the chemical conjugation of proteins

The bioconjugation of proteins—that is, the creation of a covalent link between a protein and any other molecule—has been studied for decades, partly because of the numerous applications of protein conjugates, but also due to the technical challenge it represents. Indeed, proteins possess inner phys...

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Main Authors: Charlotte Sornay, Valentine Vaur, Alain Wagner, Guilhem Chaubet
Format: Article
Language:English
Published: The Royal Society 2022-01-01
Series:Royal Society Open Science
Subjects:
Online Access:https://royalsocietypublishing.org/doi/10.1098/rsos.211563
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author Charlotte Sornay
Valentine Vaur
Alain Wagner
Guilhem Chaubet
author_facet Charlotte Sornay
Valentine Vaur
Alain Wagner
Guilhem Chaubet
author_sort Charlotte Sornay
collection DOAJ
description The bioconjugation of proteins—that is, the creation of a covalent link between a protein and any other molecule—has been studied for decades, partly because of the numerous applications of protein conjugates, but also due to the technical challenge it represents. Indeed, proteins possess inner physico-chemical properties—they are sensitive and polynucleophilic macromolecules—that make them complex substrates in conjugation reactions. This complexity arises from the mild conditions imposed by their sensitivity but also from selectivity issues, viz the precise control of the conjugation site on the protein. After decades of research, strategies and reagents have been developed to address two aspects of this selectivity: chemoselectivity—harnessing the reacting chemical functionality—and site-selectivity—controlling the reacting amino acid residue—most notably thanks to the participation of synthetic chemistry in this effort. This review offers an overview of these chemical bioconjugation strategies, insisting on those employing native proteins as substrates, and shows that the field is active and exciting, especially for synthetic chemists seeking new challenges.
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spelling doaj.art-d9c8ef81075541aba36d234c4316cb372023-04-28T11:04:05ZengThe Royal SocietyRoyal Society Open Science2054-57032022-01-019110.1098/rsos.211563An overview of chemo- and site-selectivity aspects in the chemical conjugation of proteinsCharlotte Sornay0Valentine Vaur1Alain Wagner2Guilhem Chaubet3Bio-Functional Chemistry (UMR 7199), LabEx Medalis, University of Strasbourg, 74 Route du Rhin, Illkirch-Graffenstaden 67400, FranceBio-Functional Chemistry (UMR 7199), LabEx Medalis, University of Strasbourg, 74 Route du Rhin, Illkirch-Graffenstaden 67400, FranceBio-Functional Chemistry (UMR 7199), LabEx Medalis, University of Strasbourg, 74 Route du Rhin, Illkirch-Graffenstaden 67400, FranceBio-Functional Chemistry (UMR 7199), LabEx Medalis, University of Strasbourg, 74 Route du Rhin, Illkirch-Graffenstaden 67400, FranceThe bioconjugation of proteins—that is, the creation of a covalent link between a protein and any other molecule—has been studied for decades, partly because of the numerous applications of protein conjugates, but also due to the technical challenge it represents. Indeed, proteins possess inner physico-chemical properties—they are sensitive and polynucleophilic macromolecules—that make them complex substrates in conjugation reactions. This complexity arises from the mild conditions imposed by their sensitivity but also from selectivity issues, viz the precise control of the conjugation site on the protein. After decades of research, strategies and reagents have been developed to address two aspects of this selectivity: chemoselectivity—harnessing the reacting chemical functionality—and site-selectivity—controlling the reacting amino acid residue—most notably thanks to the participation of synthetic chemistry in this effort. This review offers an overview of these chemical bioconjugation strategies, insisting on those employing native proteins as substrates, and shows that the field is active and exciting, especially for synthetic chemists seeking new challenges.https://royalsocietypublishing.org/doi/10.1098/rsos.211563bioconjugationproteinschemoselectivitysite-selectivitysynthetic chemistry
spellingShingle Charlotte Sornay
Valentine Vaur
Alain Wagner
Guilhem Chaubet
An overview of chemo- and site-selectivity aspects in the chemical conjugation of proteins
Royal Society Open Science
bioconjugation
proteins
chemoselectivity
site-selectivity
synthetic chemistry
title An overview of chemo- and site-selectivity aspects in the chemical conjugation of proteins
title_full An overview of chemo- and site-selectivity aspects in the chemical conjugation of proteins
title_fullStr An overview of chemo- and site-selectivity aspects in the chemical conjugation of proteins
title_full_unstemmed An overview of chemo- and site-selectivity aspects in the chemical conjugation of proteins
title_short An overview of chemo- and site-selectivity aspects in the chemical conjugation of proteins
title_sort overview of chemo and site selectivity aspects in the chemical conjugation of proteins
topic bioconjugation
proteins
chemoselectivity
site-selectivity
synthetic chemistry
url https://royalsocietypublishing.org/doi/10.1098/rsos.211563
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