Abstract—

The structure and thermal stability of complexes of RNA and DNA with phosphoryl guanidine oligonucleotides (PGO) bearing modified phosphate residues in which 1,3-dimethylimidazolidin-2-imine residues are introduced at the phosphorus atom have been studied. The substitution of the negatively charged oxygen atom in the structure of the internucleoside phosphate residue of an oligodeoxyribonucleotide by an electroneutral tetraalkyl-substituted guanidine residue does not lead to significant changes in the conformation of the PGO/RNA duplex compared to the native DNA/RNA complex. Their secondary structure is typical for the A-form of the double helix of hybrid complexes and differs from that of the RNA/RNA duplex. The introduction of modifications leads to a decrease in the thermal stability of PGO/RNA complexes under standard conditions (1.01 М Na⁺, neutral рН values). The magnitude of destabilization weakly depends on the nucleotide context in which the modification is located; on average, the thermal stability decreases by 1.2°С per one modified phosphate residue. The duplexes of fully substituted PGO with DNA have thermal stability that does not depend on the concentration of cations in solution. In contrast, the case of PGO/RNA complex, a significant decrease (by ~6°С) in thermal stability on changes from standard conditions to deionized water (Milli-Q) is observed. For comparison, the thermal stability of native duplexes on changes in buffer conditions decreases by more than 40°С. The changes in the thermal stability associated with the introduction of modifications are due to changes both in the enthalpy and entropy of complex formation.

中文翻译：

---

磷酸胍胍寡核苷酸与DNA和RNA杂交的比较研究

摘要-

研究了RNA和DNA与带有修饰的磷酸残基的磷酰胍寡核苷酸（PGO）的配合物的结构和热稳定性，其中在磷原子上引入了1,3-二甲基咪唑啉二-2-亚胺残基。与中性DNA / RNA复合物相比，低聚脱氧核糖核苷酸的核苷间磷酸酯残基结构中的带负电荷的氧原子被电子中性四烷基取代的胍基残基取代不会导致PGO / RNA双链体构象的显着变化。 。它们的二级结构是杂交复合物双螺旋的A型的典型结构，不同于RNA / RNA双链体的二级结构。引入修饰会导致标准条件下PGO / RNA复合物的热稳定性降低（1.01МNa⁺，中性рН值）。不稳定的程度弱地取决于修饰所位于的核苷酸背景。平均而言，每一个改性的磷酸酯残基的热稳定性降低1.2°С。具有DNA的完全取代的PGO的双链体具有不依赖于溶液中阳离子浓度的热稳定性。相反，在PGO / RNA复合物的情况下，观察到从标准条件到去离子水（Milli-Q）的变化，热稳定性显着降低（约6°С）。为了进行比较，天然双链体在缓冲条件变化时的热稳定性降低了40°С以上。与引入修饰相关的热稳定性的变化归因于复合物形成的焓和熵的变化。