10.1002/chem.201705188
Chemistry - A European Journal
FULL PAPER
Kormos, C. Koehler, G. Mező, K. Németh, E. Kozma, L. B. Takács, E.
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In this study, we present the design and synthesis of aziridine-
fused trans-cyclooctene derivatives, which produce fluorescent
products in reaction with 1,2,4,5-tetrazines. The newly
developed dienophiles adopt the ’half-chair’ conformation as a
result of the cis-ring fusion of the aziridine moiety. This highly
strained conformation leads to remarkable reactivity in the
IEDDA reactions making these compounds one of the most
reactive bioorthogonal probes known to date. Despite their high
reactivity, these compounds show good stability under various
conditions. Stability of the corresponding click products was
found to be excellent as well. We demonstrate the potential of
aza-TCOs in fluorogenic ligation reactions by the labeling of
model biomolecules and by cell imaging experiments. The
exceptional reactivity together with the intrinsic formation of
fluorescent products upon reaction with simple tetrazines make
aza-TCO dienophiles attractive candidates for fluorogenic
biomolecule tagging and bioimaging applications.
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Acknowledgements
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This work was supported by the Czech Science Foundation
(P207/15-06020Y, for M.V.), Ministry of Education Youth and
Sports of the Czech Republic (project LO1304, program “NPU-
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European Union’s Horizon 2020 research and innovation
programme (grants agreement No 677465, for M.V.). We thank
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Keywords: cell labeling • Diels-Alder reaction • fluorogenic •
trans-cyclooctene • tetrazines
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