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Fast and Efficient Postsynthetic DNA Labeling in Cells by Means of Strain‐Promoted Sydnone‐Alkyne Cycloadditions
Author(s) -
Krell Katja,
Pfeuffer Bastian,
Rönicke Franziska,
Chinoy Zoeisha S.,
Favre Camille,
Friscourt Frédéric,
Wagenknecht HansAchim
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202103026
Subject(s) - bioorthogonal chemistry , sydnone , chemistry , alkyne , cycloaddition , nucleic acid , dna , combinatorial chemistry , biochemistry , click chemistry , organic chemistry , ring (chemistry) , catalysis
Sydnones are highly stable mesoionic 1,3‐dipoles that react with cyclooctynes through strain‐promoted sydnone‐alkyne cycloaddition (SPSAC). Although sydnones have been shown to be valuable bioorthogonal chemical reporters for the labeling of proteins and complex glycans, nucleic acids have not yet been tagged by SPSAC. Evaluation of SPSAC kinetics with model substrates showed fast reactions with cyclooctyne probes (up to k =0.59 M −1 s −1 ), and two different sydnones were effectively incorporated into both 2’‐deoxyuridines at position 5, and 7‐deaza‐2’‐deoxyadenosines at position 7. These modified nucleosides were synthetically incorporated into single‐stranded DNAs, which were successfully postsynthetically labeled with cyclooctyne probes both in vitro and in cells. These results show that sydnones are versatile bioorthogonal tags and have the premise to become essential tools for tracking DNA and potentially RNA in living cells.