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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...

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Autores principales: Gavriel, Katerina, van Doeselaar, Dustin C. A., Geers, Daniëlle W. T., Neumann, Kevin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: RSC 2023
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).
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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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