Design and Synthesis of Aza-Bicyclononene Dienophiles for Rapid Fluorogenic Ligations

0489643 - ÚOCHB 2019 RIV DE eng J - Journal Article
Siegl, Sebastian J. - Vázquez, Arcadio - Dzijak, Rastislav - Dračínský, Martin - Galeta, Juraj - Rampmaier, Robert - Klepetářová, Blanka - Vrábel, Milan
Design and Synthesis of Aza-Bicyclononene Dienophiles for Rapid Fluorogenic Ligations.
Chemistry - A European Journal. Roč. 24, č. 10 (2018), s. 2426-2432. ISSN 0947-6539. E-ISSN 1521-3765
R&D Projects: GA ČR GJ15-06020Y; GA MŠMT(CZ) LO1304
EU Projects: European Commission(XE) 677465 - SWEETOOLS
Institutional support: RVO:61388963
Keywords : cell labeling * Diels-Alder reaction * fluorogenic * tetrazines * trans-cyclooctene
OECD category: Organic chemistry
Impact factor: 5.160, year: 2018

Fluorogenic bioorthogonal reactions enable visualization of biomolecules under native conditions with excellent signal-to-noise ratio. Here, we present the design and synthesis of conformationally-strained aziridine-fused trans-cyclooctene (aza-TCO) dienophiles, which lead to the formation of fluorescent products in tetrazine ligations without the need for attachment of an extra fluorophore moiety. The presented aza-TCOs adopt the highly strained “half-chair” conformation, which was predicted computationally and confirmed by NMR measurements and X-ray crystallography. Kinetic studies revealed that the aza-TCOs belong to the most reactive dienophiles known to date. The potential of the newly developed aza-TCO probes for bioimaging applications is demonstrated by protein labeling experiments, imaging of cellular glycoconjugates and peptidoglycan imaging of live bacteria.
Permanent Link: http://hdl.handle.net/11104/0284018