Buhr C A, Wagner R W, Grant D, Froehler B C
Gilead Sciences, Foster City, CA 94404, USA.
Nucleic Acids Res. 1996 Aug 1;24(15):2974-80. doi: 10.1093/nar/24.15.2974.
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.
本文描述了含有7-(1-丙炔基)-7-脱氮-2'-脱氧鸟苷(pdG)和7-(1-丙炔基)-7-脱氮-2'-脱氧腺苷(pdA)的寡脱氧核苷酸(ODN)的合成、杂交特性及反义活性。合成了适当保护的核苷并将其掺入ODN中。这些与RNA杂交的ODN的热变性(Tm)表明,相对于7-未取代的脱氮嘌呤和未修饰的ODN对照,其稳定性有所提高。通过可控微注射试验测定了这些ODN的反义抑制作用,结果表明,含pdG的ODN活性约为未修饰ODN的6倍。7-丙炔基-7-脱氮-2'-脱氧鸟苷是开发高效反义ODN的一种有前景的先导类似物。