Boggon T J, Hancox E L, McAuley-Hecht K E, Connolly B A, Hunter W N, Brown T, Walker R T, Leonard G A
Department of Chemistry, University of Manchester, UK.
Nucleic Acids Res. 1996 Mar 1;24(5):951-61. doi: 10.1093/nar/24.5.951.
The crystal structure refinement of the synthetic dodecamer d(CGCGAASSCGCG), where S = 4'-thio-2'-deoxythymidine, has converged at R=0.201 for 2605 reflections with F > 2sigma(F) in the resolution range 8.0-2.4 A for a model consisting of the dodecamer duplex and 66 water molecules. A comparison of its structure with that of the native dodecamer d(CGCGAATTCGCG) has revealed that the major differences between the two structures is a change in the conformation of the sugar-phosphate backbone in the regions at and adjacent to the positions of the modified nucleosides. Examination of the fine structural parameters for each of the structures reveals that the thiosugars adopt a C3'-exo conformation in d(CGCGAASSCGCG), rather than the approximate C1'-exo conformation found for the analogous sugars in the structure of d(CGCGAATTCGCG). The observed differences in structure between the two duplexes may help to explain the enhanced resistance to nuclease digestion of synthetic oligonucleotides containing 4'-thio-2'-deoxynucleotides.
合成的十二聚体d（CGCGAASSCGCG）（其中S = 4'-硫代-2'-脱氧胸苷）的晶体结构精修在分辨率范围为8.0 - 2.4 Å时，对于由十二聚体双链体和66个水分子组成的模型，2605个F > 2σ（F）的反射的R值收敛到0.201。将其结构与天然十二聚体d（CGCGAATTCGCG）的结构进行比较后发现，这两种结构之间的主要差异在于修饰核苷位置及相邻区域的糖 - 磷酸主链构象发生了变化。对每种结构的精细结构参数进行检查发现，硫代糖在d（CGCGAASSCGCG）中采用C3'-外向构象，而不是在d（CGCGAATTCGCG）结构中类似糖所发现的近似C1'-外向构象。观察到的两种双链体之间的结构差异可能有助于解释含4'-硫代-2'-脱氧核苷酸的合成寡核苷酸对核酸酶消化的抗性增强。
