Balow G, Mohan V, Lesnik E A, Johnston J F, Monia B P, Acevedo O L
Department of Medicinal Chemistry and Antisense Biology, Isis Pharmaceuticals Inc., Carlsbad, CA 92008, USA.
Nucleic Acids Res. 1998 Jul 15;26(14):3350-7. doi: 10.1093/nar/26.14.3350.
The synthesis of 7-propynyl-, 7-iodo- and 7-cyano-7-deaza-2-amino-2'-deoxyadenosines is described. The nucleosides were synthesized, functionalized into the phosphoramidites and incorporated into oligodeoxynucleotides. Spectroscopic melting experiments against complementary RNA showed increases of 3-4 degreesC per modification for single substitutions and smaller increases per incorporation for multiple substitutions relative to unmodified control sequences. The 7-propyne and 7-iodo nucleosides 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 increase in potency over unmodifed controls.
描述了7-丙炔基-、7-碘代-和7-氰基-7-脱氮-2-氨基-2'-脱氧腺苷的合成。合成了核苷，将其官能化为亚磷酰胺并掺入到寡脱氧核苷酸中。针对互补RNA的光谱熔解实验表明，与未修饰的对照序列相比，单取代时每次修饰的熔解温度升高3-4℃，多取代时每次掺入的熔解温度升高较小。将7-丙炔基和7-碘代核苷掺入靶向小鼠C-raf mRNA 3'-UTR的反义序列中。两种核苷均表现出取代依赖性效力。具有三个和四个7-丙炔基-7-脱氮-2-氨基-2'-脱氧腺苷取代的序列相对于未修饰的对照显示出2-3倍的效力增加。
