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

Abstract

The synthesis and properties of oligodeoxynucleotides (ODNs) containing 2'-O-(trifluoromethyl)adenosine (2) are described. 2'-O-(Trifluoromethyl)adenosine (2) or N6-(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-tetraisopropyldisil-oxane-1,3 -diyl)(TIPDS)adenosine (4) or N6,N6-(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.