Effects of 2'-O-(trifluoromethyl)adenosine on oligodeoxynucleotide hybridization and nuclease stability

The synthesis and properties of oligodeoxynucleotides (ODNs) containing 2'- O -(trifluoromethyl)adenosine (2) are described. 2'- O -(Trifluoromethyl)adenosine (2) or N 6-(benzoyl)-2'- O -(trifluoromethyl)adenosine (6) was obtained in 22 or 32% yield by treating 2'- O -[(methylthio)thiocarbonyl]-3',5'- O -(1,1,3, 3-tetraisopropyldisiloxane-1,3-diyl)(TIPDS)adenosine (4) or N 6, N 6-(dibenzoyl)-2'- O -[(methylthio)thiocarbonyl]-3',5'- O -(TIPDS)-adenosine (5), respectively, with pyridinium poly-(hydrogen fluoride) in the presence of 1,3-dibromo-5,5-dimethylhydantoin. Nucleoside 2 was incorporated into DNA hexadecamers. ODNs that contained 2 reduced the thermal stability of duplexes with their complementary DNAs but increased the thermal stability of duplexes with their complementary RNAs. Furthermore, ODNs containing 2 were slightly more resistant to snake venom phosphodiesterase than an unmodified ODN.