Abstract
This work presents a new version of synthetic analogues of oligonucleotides containing two types of modifications – phosphoryl guanidine (PG) internucleotide group and 2ʹ,4ʹ-locked ribose fragments (LNA) – in one nucleotide unit. It has been shown the presence of PG-LNA linkages decreases the electrophoretic mobility of the oligonucleotides, primarily due to the electroneutrality of the PG group. Additionally, the PG-LNA modifications increase the hydrophobicity of the oligonucleotides, resulting in longer retention times during reversed-phase chromatography. The thermal stability of complementary duplexes containing PG-LNA oligonucleotides has been investigated. It was found the melting temperature increases by 1.5–4.0°C per modification, depending on the position of the modified unit and the ionic strength of the solution. Furthermore, circular dichroism spectropolarimetry revealed the secondary structure of the complexes formed by PG-LNA differs from the B-form, which may be attributed to the presence of LNA fragments exhibiting a 3'-endo conformation of the ribose ring. Thus, PG-LNA oligonucleotides can be considered as a new structural analogue of RNA with partially uncharged backbone. Based on the data obtained, it can be concluded that PG-LNA oligonucleotides can be considered as a promising tool for various methods of isolation and analysis of nucleic acids.