PMID- 37654505
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230902
IS  - 2633-0679 (Electronic)
IS  - 2633-0679 (Linking)
VI  - 4
IP  - 9
DP  - 2023 Aug 30
TI  - Click'n lock: rapid exchange between unsymmetric tetrazines and thiols for 
      reversible, chemoselective functionalisation of biomolecules with on-demand 
      bioorthogonal locking.
PG  - 685-691
LID - 10.1039/d3cb00062a [doi]
AB  - 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).
CI  - This journal is (c) The Royal Society of Chemistry.
FAU - Gavriel, Katerina
AU  - Gavriel K
AD  - Systems Chemistry Department, Institute for Molecules and Materials, Radboud 
      University Nijmegen Heyendaalseweg 135 6525 AJ Nijmegen The Netherlands 
      kevin.neumann@ru.nl.
FAU - van Doeselaar, Dustin C A
AU  - van Doeselaar DCA
AD  - Systems Chemistry Department, Institute for Molecules and Materials, Radboud 
      University Nijmegen Heyendaalseweg 135 6525 AJ Nijmegen The Netherlands 
      kevin.neumann@ru.nl.
FAU - Geers, Danielle W T
AU  - Geers DWT
AD  - Systems Chemistry Department, Institute for Molecules and Materials, Radboud 
      University Nijmegen Heyendaalseweg 135 6525 AJ Nijmegen The Netherlands 
      kevin.neumann@ru.nl.
FAU - Neumann, Kevin
AU  - Neumann K
AUID- ORCID: 0000-0002-6683-0774
AD  - Systems Chemistry Department, Institute for Molecules and Materials, Radboud 
      University Nijmegen Heyendaalseweg 135 6525 AJ Nijmegen The Netherlands 
      kevin.neumann@ru.nl.
LA  - eng
PT  - Journal Article
DEP - 20230720
PL  - England
TA  - RSC Chem Biol
JT  - RSC chemical biology
JID - 101768727
PMC - PMC10467616
COIS- There are no conflicts to declare.
EDAT- 2023/09/01 06:43
MHDA- 2023/09/01 06:44
PMCR- 2023/07/20
CRDT- 2023/09/01 03:56
PHST- 2023/05/04 00:00 [received]
PHST- 2023/07/19 00:00 [accepted]
PHST- 2023/09/01 06:44 [medline]
PHST- 2023/09/01 06:43 [pubmed]
PHST- 2023/09/01 03:56 [entrez]
PHST- 2023/07/20 00:00 [pmc-release]
AID - d3cb00062a [pii]
AID - 10.1039/d3cb00062a [doi]
PST - epublish
SO  - RSC Chem Biol. 2023 Jul 20;4(9):685-691. doi: 10.1039/d3cb00062a. eCollection 
      2023 Aug 30.