2',5'-linked oligo-3'-deoxyribonucleoside phosphorothioate chimeras: thermal stability and antisense inhibition of gene expression
2',5'-linked oligo-3'-deoxyribonucleoside phosphorothioate chimeras: thermal stability and antisense inhibition of gene expression
复制标题
DOI：
10.1093/nar/25.16.3310
复制
发表时间：
1997-08-15
影响因子：
14.9
通讯作者：
Hoke, GD
中科院分区：
文献类型：
--
作者：
Bhan, P;Bhan, A;Hoke, GD
2',5'-连接的寡-3'-脱氧核糖核苷酸选择性地与互补 RNA 结合，但不与 DNA 结合。这些寡核苷酸 (ODN) 不会通过 Hoogsteen 三联体形成来识别双链 DNA，并且这些 ODN 与 RNA 形成的复合物不是大肠杆菌 RNase H 的底物。用硫代磷酸酯键取代 2',5'-磷酸二酯主链可产生 2',5'-连接寡聚 3'-脱氧核苷硫代磷酸酯 ODN 与细胞蛋白或凝血酶的非特异性结合显着减少，在 2',5'-连接的 ODN 中心（作为假定的 RNase H 识别位点）掺入一段七个连续的 3',5'-连接的寡聚-2'-脱氧核苷硫代磷酸酯键（作为推定的 RNase H 识别位点），提供嵌合反义 ODN，保留抑制类固醇的能力细胞培养物中的 5α-还原酶 (5αR) 表达。
2',5'-Linked oligo-3'-deoxyribonucleotides bind selectively to complementary RNA but not to DNA, These oligonucleotides (ODNs) do not recognize double-stranded DNA by Hoogsteen tripler formation and the complexes formed by these ODNs with RNA are not substrates for Escherichia coli RNase H. Substitution of the 2',5'-phosphodiester backbone by phosphorothioate linkages gives 2',5'-linked oligo-3'-deoxynucleoside phosphorothioate ODNs that exhibit significantly less non-specific binding to cellular proteins or thrombin, Incorporation of a stretch of seven contiguous 3',5'-linked oligo-2'-deoxynucleoside phosphorothioate linkages in the center of 2',5'-linked ODNs (as a putative RNase H recognition site) afford chimeric antisense ODNs that retain the ability to inhibit steroid 5 alpha-reductase (5 alpha R) expression in cell culture.