Oligodeoxynucleotides containing C-7 propyne analogs of 7-deaza-2'- deoxyguanosine and 7-deaza-2'-deoxyadenosine

Abstract
The synthesis, hybridization properties and antisense activities of oligodeoxynucleotides (ODNs) containing 7-(1-propynyl)-7-deaza-2′ -deoxyguanosine (pdG) and 7-(1-propynyl)-7-deaza-2′ -deoxyadenosine (pdA) are described. The suitably protected nucleosides were synthesized and incorporated into ODNs. Thermal denaturation (Tm) of these ODNs hybridized to RNA demonstrates an increased stability relative to 7-unsubstituted deazapurine and unmodified ODN controls. Antisense inhibition by these ODNs was determined in a controlled microinjection assay and the results demonstrate that an ODN containing pdG is ∼6 times more active than the unmodified ODN. 7-Propyne-7-deaza-2′-deoxyguanosine is a promising lead analog for the development of antisense ODNs with increased potency.