BIOPHYSICAL AND ANTISENSE PROPERTIES OF OLIGODEOXYNUCLEOTIDES CONTAINING 7-PROPYNYL-7-DEAZA-2-AMINO-2'-DEOXYADENOSINES, 7-IODO-7-DEAZA-2-AMINO-2'-DEOXYADENOSINES AND 7-CYANO-7-DEAZA-2-AMINO-2'-DEOXYADENOSINES

The synthesis of 7-propynyl-, 7-iodo- and 7-cyano-7-deaza-2-amino-2'-d eoxyadenosines is described. The nucleosides were synthesized, functio nalized into the phosphoramidites and incorporated into oligodeoxynucl eotides, Spectroscopic melting experiments against complementary RNA s howed increases of 3-4 degrees C per modification for single substitut ions and smaller increases per incorporation for multiple substitution s relative to unmodified control sequences. The-7-propyne and 7-iodo n ucleosides were incorporated into antisense sequences targeting the 3' -UTR of murine C-raf mRNA, Both nucleosides demonstrated substitution- dependent potency. The sequences with three and four substitutions of the 7-propyne-7-deaza-2-amino-2'-deoxyadenosine exhibited a 2-3-fold i ncrease in potency over unmodifed controls.