title: 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 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.
authors: Gilead Sciences, Foster City, CA 94404, USA.
authors: C A
authors: CA
authors: Buhr
authors: R W
authors: RW
authors: Wagner
authors: D
authors: D
authors: Grant
authors: B C
authors: BC
authors: Froehler
mesh_terms: 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
chemical_list: 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