Strain Promoted Click Chemistry of 2- or 8-Azidopurine and 5-Azidopyrimidine Nucleosides and 8-Azidoadenosine Triphosphate with Cyclooctynes. Application to Living Cell Fluorescent Imaging

Authors

Jessica Zayas, Department of Chemistry and Biochemistry, Florida International University
Marie Annoual, Department of Chemistry and Biochemistry, Florida International UniversityFollow
Jayanta K. Das, Department of Environmental & Occupational Health, Florida International UniversityFollow
Quentin Felty, Department of Environmental & Occupational Health, Florida International UniversityFollow
Walter Gonzalez, Biomolecular Sciences Institute and Department of Chemistry and Biochemistry, Florida International UniversityFollow
Jaroslava Miksovska, Biomolecular Sciences Institute and Department of Chemistry and Biochemistry, Florida International UniversityFollow
Nima Sharifai, University of Miami
Akira Chiba, University of Miami
Stanislaw F. Wnuk, Department of Chemistry and Biochemistry and Department of Environmental and Occupational Health, Florida International UniversityFollow

Date of this Version

8-2015

Document Type

Article

Abstract

Strain-promoted click chemistry of nucleosides and nucleotides with an azido group directly attached to the purine and pyrimidine rings with various cyclooctynes in aqueous solution at ambient temperature resulted in efficient formation (3 min to 3 h) of fluorescent, light-up, triazole products. The 2- and 8-azidoadenine nucleosides reacted with fused cyclopropyl cyclooctyne, dibenzylcyclooctyne, or monofluorocyclooctyne to produce click products functionalized with hydroxyl, amino, N-hydroxysuccinimide, or biotin moieties. The 5-azidouridine and 5-azido-2'-deoxyuridine were similarly converted to the analogous triazole products in quantitative yields in less than 5 min. The 8-azido-ATP quantitatively afforded the triazole product with fused cyclopropyl cyclooctyne in aqueous acetonitrile (3 h). The novel triazole adducts at the 2- or 8-position of adenine or 5-position of uracil rings induce fluorescence properties which were used for direct imaging in MCF-7 cancer cells without the need for traditional fluorogenic reporters. FLIM of the triazole click adducts demonstrated their potential utility for dynamic measuring and tracking of signaling events inside single living cancer cells.

Comments

Published in final edited form in Bioconjugate Chemistry.

Identifier

FIDC006497

Rights

default

Recommended Citation

Zayas, Jessica; Annoual, Marie; Das, Jayanta K.; Felty, Quentin; Gonzalez, Walter; Miksovska, Jaroslava; Sharifai, Nima; Chiba, Akira; and Wnuk, Stanislaw F., "Strain Promoted Click Chemistry of 2- or 8-Azidopurine and 5-Azidopyrimidine Nucleosides and 8-Azidoadenosine Triphosphate with Cyclooctynes. Application to Living Cell Fluorescent Imaging" (2015). Environmental Health Sciences. 13.
https://digitalcommons.fiu.edu/eoh_fac/13