Bellon L, Barascut J L, Maury G, Divita G, Goody R, Imbach J L
Laboratoire de Chimie Bio-organique, UA 488 CNRS, Université Montpellier II, France.
Nucleic Acids Res. 1993 Apr 11;21(7):1587-93. doi: 10.1093/nar/21.7.1587.
We present the synthesis and the study of properties of a new series of modified oligonucleotides, namely 4'-thio-oligo-beta-D-ribonucleotides (4'-S-RNA). Homo-oligonucleotides of this class (4'-SU6 and 4'-SU12) were prepared from the previously known thionucleosides using the phosphoramidite methodology. The comparison of the substrate properties of 4'-SU6 and its natural analog U6 with respect to four nucleases indicates that the former is much more resistant than the latter. Such resistance to nucleases in addition to relatively high Tm values for 4'-SU12 hybridized with Poly(A) show that these new 4'-S-RNA are good candidates for potential antisense effects. The oligonucleotides 4'-SU6 and 4'-SU12 have been also evaluated as non sequence specific inhibitors of HIV-1 reverse transcriptase. All available evidences, based primarily on fluorescence measurements, are consistent with the binding of 4'-SU6 and 4'-SU12 to RT at a site which is different from the polymerase site of the enzyme.
我们展示了一系列新的修饰寡核苷酸,即4'-硫代-寡聚-β-D-核糖核苷酸(4'-S-RNA)的合成及其性质研究。此类同型寡核苷酸(4'-SU6和4'-SU12)是使用亚磷酰胺方法由先前已知的硫代核苷制备的。4'-SU6及其天然类似物U6相对于四种核酸酶的底物性质比较表明,前者比后者具有更高的抗性。除了与聚(A)杂交的4'-SU12具有相对较高的Tm值外,这种对核酸酶的抗性表明这些新的4'-S-RNA是潜在反义效应的良好候选物。寡核苷酸4'-SU6和4'-SU12也已被评估为HIV-1逆转录酶的非序列特异性抑制剂。所有主要基于荧光测量的现有证据都与4'-SU6和4'-SU12在与该酶的聚合酶位点不同的位点与逆转录酶结合一致。