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Click’n lock: rapid exchange between unsymmetric tetrazines and thiols for reversible, chemoselective functionalisation of biomolecules with on-demand bioorthogonal locking
The late-stage functionalisation and diversification of complex structures including biomolecules is often achieved with the help of click chemistry. Besides employing irreversible click-like reactions, many synthetic applications benefit from reversible click reaction strategies, so called de-/tran...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
RSC
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10467616/ https://www.ncbi.nlm.nih.gov/pubmed/37654505 http://dx.doi.org/10.1039/d3cb00062a |
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author | Gavriel, Katerina van Doeselaar, Dustin C. A. Geers, Daniëlle W. T. Neumann, Kevin |
author_facet | Gavriel, Katerina van Doeselaar, Dustin C. A. Geers, Daniëlle W. T. Neumann, Kevin |
author_sort | Gavriel, Katerina |
collection | PubMed |
description | The late-stage functionalisation and diversification of complex structures including biomolecules is often achieved with the help of click chemistry. Besides employing irreversible click-like reactions, many synthetic applications benefit from reversible click reaction strategies, so called de-/trans-click approaches. Yet, the combination of both, reversible and irreversible click chemistry – while still respecting the stringent criteria of click transformations – remains so far elusive for modifications of biomolecular structures. Here, we report click’n lock as a concept that enables reversible click reactions and on-demand locking of chemical entities, thus switching from reversible to irreversible modifications of complex biomolecules. For this purpose, we employ the tetrazine–thiol exchange (TeTEx) reaction as a fully traceless click reaction with second order rate constants k(2) higher than 2 M(−1) s(−1) within aqueous environments. Employing TeTEx as a reversible click reaction for the chemoselective modification of biomolecules is made possible by the use of 3,6-disubstituted 1,2,4,5-tetrazines bearing a single sulfide residue. The inherent reactivity of tetrazines towards inverse electron demand Diels–Alder (IEDDA) reactions allows to stabilize the clicked structure, switching from reversible to irreversible systems (click’n lock). |
format | Online Article Text |
id | pubmed-10467616 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | RSC |
record_format | MEDLINE/PubMed |
spelling | pubmed-104676162023-08-31 Click’n lock: rapid exchange between unsymmetric tetrazines and thiols for reversible, chemoselective functionalisation of biomolecules with on-demand bioorthogonal locking Gavriel, Katerina van Doeselaar, Dustin C. A. Geers, Daniëlle W. T. Neumann, Kevin RSC Chem Biol Chemistry The late-stage functionalisation and diversification of complex structures including biomolecules is often achieved with the help of click chemistry. Besides employing irreversible click-like reactions, many synthetic applications benefit from reversible click reaction strategies, so called de-/trans-click approaches. Yet, the combination of both, reversible and irreversible click chemistry – while still respecting the stringent criteria of click transformations – remains so far elusive for modifications of biomolecular structures. Here, we report click’n lock as a concept that enables reversible click reactions and on-demand locking of chemical entities, thus switching from reversible to irreversible modifications of complex biomolecules. For this purpose, we employ the tetrazine–thiol exchange (TeTEx) reaction as a fully traceless click reaction with second order rate constants k(2) higher than 2 M(−1) s(−1) within aqueous environments. Employing TeTEx as a reversible click reaction for the chemoselective modification of biomolecules is made possible by the use of 3,6-disubstituted 1,2,4,5-tetrazines bearing a single sulfide residue. The inherent reactivity of tetrazines towards inverse electron demand Diels–Alder (IEDDA) reactions allows to stabilize the clicked structure, switching from reversible to irreversible systems (click’n lock). RSC 2023-07-20 /pmc/articles/PMC10467616/ /pubmed/37654505 http://dx.doi.org/10.1039/d3cb00062a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Gavriel, Katerina van Doeselaar, Dustin C. A. Geers, Daniëlle W. T. Neumann, Kevin Click’n lock: rapid exchange between unsymmetric tetrazines and thiols for reversible, chemoselective functionalisation of biomolecules with on-demand bioorthogonal locking |
title |
Click’n lock: rapid exchange between unsymmetric tetrazines and thiols for reversible, chemoselective functionalisation of biomolecules with on-demand bioorthogonal locking |
title_full |
Click’n lock: rapid exchange between unsymmetric tetrazines and thiols for reversible, chemoselective functionalisation of biomolecules with on-demand bioorthogonal locking |
title_fullStr |
Click’n lock: rapid exchange between unsymmetric tetrazines and thiols for reversible, chemoselective functionalisation of biomolecules with on-demand bioorthogonal locking |
title_full_unstemmed |
Click’n lock: rapid exchange between unsymmetric tetrazines and thiols for reversible, chemoselective functionalisation of biomolecules with on-demand bioorthogonal locking |
title_short |
Click’n lock: rapid exchange between unsymmetric tetrazines and thiols for reversible, chemoselective functionalisation of biomolecules with on-demand bioorthogonal locking |
title_sort | click’n lock: rapid exchange between unsymmetric tetrazines and thiols for reversible, chemoselective functionalisation of biomolecules with on-demand bioorthogonal locking |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10467616/ https://www.ncbi.nlm.nih.gov/pubmed/37654505 http://dx.doi.org/10.1039/d3cb00062a |
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