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

Abstract

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-fluoro substitution leads to increased duplex stability and more selective base pairing compared to the non-functionalized 7-deazapurine oligonucleotides. F-19 NMR spectra of fluorinated nucleosides, single stranded oligonucleotides and DNA duplex show only a single signal for one fluorine modification. The NMR sensitive F-19 spin or the positron emitting F-18 isotope make these compounds applicable for DNA detection or imaging in vitro and in vivo.