Oligodeoxynucleotides containing C-7 propyne analogs of 7-deaza-2'-deoxyguanosine and 7-deaza-2'-deoxyadenosine.
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 approximately 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.
Buhr
C A
CA
Gilead Sciences, Foster City, CA 94404, USA.
Wagner
R W
RW
Grant
D
D
Froehler
B C
BC
D001483:Base Sequence; D016373:DNA, Antisense / Q000737:chemistry* / Q000235:genetics; D003839:Deoxyadenosines / Q000737:chemistry*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000235:genetics
C101165:7-(1-propynyl)-7-deaza-2'-deoxyadenosine; C101164:7-(1-propynyl)-7-deaza-2'-deoxyguanosine; D016373:DNA, Antisense; D003839:Deoxyadenosines; D009692:Nucleic Acid Heteroduplexes; D009838:Oligodeoxyribonucleotides; D003849:Deoxyguanosine