Tetrapeptides based on amino acids involved in the catalytic site of RNase T1 were synthe sized. These peptides interact with a 96 mer fragment of HIV 1 RNA, which results in phosphodiester bonds splitting. The efficacy of RNA cleavage depends on the mutual arrange ment of oppositely charged amino acids (Glu and Arg or Lys) in a peptide. The introduction of an additional cationic fragment (based on bis quaternary salts of 1,4 diazabicyclooctane) into an RNase mimetic leads to a considerable increase in the efficiency of RNA depolymerization.
Phosphodiester bonds in RNA situated between similar nucleotides but in different sequences (context) were split under the action of artificial and natural ribonucleases with different speeds, and the reason for this phenomenon has not yet been fully revealed. In this study, the influence of one-nucleotide substitution on the sensitivity to splitting of the phosphodiester bonds in linear and structured RNA with homologous sequences is studied for the first time. It is indicated that the introduction of one-nucleotide substitution in the RNA sequence significantly (up to 10 times) changes the speed of the splitting of the bonds that are separated from the substitution point not only by 1-3, but also 6-8 nucleotides, by artificial ribonucleases. The observed regularities may be explained by the fact that the introduction of a one-nucleotide substitution significantly changes the stacking interactions and the net of hydrogen bonds in the RNA molecule. The applied value of this study consists of the ability of using low-molecular artificial ribonucleases with the aim of choosing the region of the binding of the oligonucleotide in the construction of a conjugate for the site-directed cutting of RNA, because the choice of a phosphodiester bond (motif) easily subjected to splitting significantly determines the effectiveness of artificial ribonucleases of directed action.
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