A Comparative Study of the Hybridization of Phosphoryl Guanidine Oligonucleotides with DNA and RNA

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.