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Fluorophosphate Nucleotide Analogs and Their Characterization as Tools for 19F NMR Studies

Baranowski, M. R. and Nowicka, A. and Rydzik, A. M. and Warminski, M. and Kasprzyk, R. and Wojtczak, B.A. and Wójcik, Jacek and Claridge, T. D. W. and Kowalska, J. and Jemielity, Jacek (2015) Fluorophosphate Nucleotide Analogs and Their Characterization as Tools for 19F NMR Studies. Journal of Organic Chemistry, 80 (8). pp. 3982-3997. ISSN ISSN: 0022-3263

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Official URL: http://pubs.acs.org/journal/joceah


To broaden the scope of existing methods based on 19F nucleotide labeling, we developed a new method for the synthesis of fluorophosphate (oligo)nucleotide analogues containing an O to F substitution at the terminal position of the(oligo)phosphate moiety and evaluated them as tools for 19F NMR studies. Using three efficient and comprehensive synthetic approaches based on phosphorimidazolide chemistry and tetra-n-butylammonium fluoride, fluoromonophosphate, or fluorophosphate imidazolide as fluorine sources, we prepared over 30 fluorophosphate-containing nucleotides, varying in nucleobase type (A, G, C, U, m7G), phosphate chain length (from mono to tetra), and presence of additional phosphate modifications (thio, borano, imido, methylene). Using fluorophosphate imidazolide as fluorophosphorylating reagent for 5′-phosphorylated oligos we also synthesized oligonucleotide 5′-(2-fluorodiphosphates), which are potentially useful as 19F NMR hybridization probes. The compounds were characterized by 19F NMR and evaluated as 19F NMR molecular probes. We found that fluorophosphate nucleotide analogues can be used to monitor activity of enzymes with various specificities and metal ion requirements, including human DcpS enzyme, a therapeutic target for spinal muscular atrophy. The compounds can also serve as reporter ligands for protein binding studies, as exemplified by studying interaction of fluorophosphate mRNA cap analogues with eukaryotic translation initiation factor (eIF4E).

Item Type:Article
Subjects:Q Science > QD Chemistry
Divisions:Laboratory of Biological NMR
ID Code:1010
Deposited By: dr hab. Jacek Wójcik
Deposited On:10 Nov 2015 15:29
Last Modified:01 Mar 2018 11:32

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