OLIGODEOXYNUCLEOTIDES CONTAINING C-7 PROPYNE ANALOGS OF 7-DEAZA-2'-DEOXYGUANOSINE AND 7-DEAZA-2'-DEOXYADENOSINE

The synthesis, hybridization properties and antisense activities of ol igodeoxynucleotides (ODNs) containing 7-(1-propynyl)-7-deaza-2'-deoxyg uanosine (pdG) and 7-(1-propynyl)-7-deaza-2'-deoxyadenosine (pdA) are described. The suitably protected nucleosides were synthesized and inc orporated into ODNs. Thermal denaturation (T-m) of these ODNs hybridiz ed to RNA demonstrates an increased stability relative to 7-unsubstitu ted deazapurine and unmodified ODN controls. Antisense inhibition by t hese ODNs was determined in a controlled microinjection assay and the results demonstrate that an ODN containing pdG is similar to 6 times m ore active than the unmodified ODN. 7-Propyne-7-deaza-2'-deoxyguanosin e is a promising lead analog for the development of antisense ODNs wit h increased potency.