DNA with stable fluorinated dA and dG substitutes: syntheses, base pairing and ~(19)F-NMR spectra of 7-fluoro-7-deaza-2'-deoxyadenosine and 7-fluoro-7-deaza-2'-deoxyguanosine

摘要

Fluorinated DNA containing stable fluorine substituents in the "purine" base were synthesized for the first time. For this, the phosphoramidites of 7-fluoro-7-deaza-2'-deoxyadenosine and 7-fluoro-7-deaza-2'-deoxyguanosine were prepared and oligonucleotides were synthesized. The 7-fiuoro substitution leads to increased duplex stability and more selective base pairing compared to the non-functionalized 7-deazapurine oligonucleotides. ~(19)F NMR spectra of fluorinated nucleosides, single stranded oligonucleotides and DNA duplex show only a single signal for one fluorine modification. The NMR sensitive ~(19)F spin or the positron emitting ~(18)F isotope make these compounds applicable for DNA detection or imaging in vitro and in vivo.