Cover Feature: Fast and Efficient Postsynthetic DNA Labeling in Cells by Means of Strain‐Promoted Sydnone‐Alkyne Cycloadditions (Chem. Eur. J. 65/2021)

Katja Krell,Bastian Pfeuffer,Camille Favre,Frédéric Friscourt,Hans‐Achim Wagenknecht,Franziska Rönicke,Zoeisha S Chinoy

doi:10.1002/chem.202103947

Abstract

DNA strands, modified with the novel bioorthogonal reporter sydnone, undergo fast and efficient labeling with cyclooctyne–dye conjugates, both in vitro and in HeLa 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. More information can be found in the Communication by F. Friscourt, H.-A. Wagenknecht et al. (DOI: 10.1002/chem.202103026).

Highlights

Sydnones are highly stable mesoionic 1,3-dipoles that react with cyclooctynes through strain-promoted sydnone-alkyne cycloaddition (SPSAC)
Among the various reported bioorthogonal chemistry, strain-promoted alkyne–azide cycloadditions (SPAAC),[2] inverse electron-demand Diels-Alder reactions[3] or photoinduced cycloadditions between tetrazoles and alkenes[4] have the advantage of alleviating the need for potentially cytotoxic metal species
In order to solve the stability shortcomings of previous bioorthogonal reagents (i. e., azides can be subject to reduction in biological systems[5]), we and others have recently demonstrated that sydnones, highly stable mesoionic 1,3-dipoles, can react with cyclooctynes through strain-promoted sydnonealkyne cycloaddition (SPSAC), for the labeling of proteins[6] and complex glycans.[5]

Summary

Introduction

Sydnones are highly stable mesoionic 1,3-dipoles that react with cyclooctynes through strain-promoted sydnone-alkyne cycloaddition (SPSAC). We present the synthesis of four different 2’-deoxynucleosides 1–4 modified with sydnones, their SPSAC reactivity with cyclooctyne probes, including the compatibility of sydnone reporters with oligonucleotides and the postsynthetic labeling of DNA in vitro and in fixed cells. The model sydnone-modified nucleosides 1 and 2 were labeled with BCN (11) and the SPSACs were followed by UV/Vis absorbance changes (Figure 3).

Results

Conclusion