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Fast and Efficient Postsynthetic DNA Labeling in Cells by Means of Strain-Promoted Sydnone-Alkyne Cycloadditions

Krell, K.; Pfeuffer, B.; Rönicke, F.; Chinoy, Z. S.; Favre, C.; Friscourt, F.; Wagenknecht, H.-A.

Abstract:
Fast and efficient: DNA strands, modified with the novel bioorthogonal reporters sydnones, undergo fast and efficient labeling with cyclooctynes and have the potential to become essential tools for imaging DNA and possibly RNA in cells.

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.


Verlagsausgabe §
DOI: 10.5445/IR/1000139755
Veröffentlicht am 12.11.2021
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Organische Chemie (IOC)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2021
Sprache Englisch
Identifikator ISSN: 0947-6539, 1521-3765
KITopen-ID: 1000139755
Erschienen in Chemistry - A European Journal
Verlag John Wiley and Sons
Nachgewiesen in Scopus
Web of Science
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