[Chemical ribonucleases. 4. Analysis of the fragment structure of chemical ribonucleases based on 1,4-diazabicyclo[2.2.2]octane]. / Khimicheskie ribonukleazy. 4. Analiz fragmentnoi struktury khimicheskikh ribonukleaz na osnove 1,4-diazabitsiklo[2.2.2]oktana.

Artificial ribonucleases of the ABLkCm series were synthesized. They consist of a lipophilic alkyl radical (Et, n-C14H29, or C15H31) A, an "RNA-binding domain" B (bisquaternary salt of 1,4-diazabicyclo[2.2.2]octane), a "catalytic domain" Cm [histamine (C1) or histidine (C3) residue], and a "linker" Lk that joins the "domains" B and Cm [here, k is the number of methylene units (one or three) in the linker]. The effect of the "domain structure" on the catalytic properties of the chemical ribonucleases was analyzed using seven compounds of this series (ABL1C1, ABL3C1, ABL3C3, AC1, AB, BL2, and BL3C3). The catalytic activity of the compounds was assessed in the reaction of hydrolysis of the in vitro transcripts of human tRNA(Lys) and yeast tRNA(Asp) under physiological conditions. It was shown that only chemical ribonucleases that involve all the fragments of the ABLkCm construct can hydrolyze the substrate tRNA at a high rate (90% of tRNA is hydrolyzed for 10 h at 37 degrees C). The activity of the compounds is largely determined by the presence of a long lipophilic radical linked to 1,4-diazabicyclo[2.2.2]octane and a long linker, which joins the RNA-hydrolyzing and RNA-binding fragments. The results indicate an important role of hydrophobic interactions in the acceleration of the RNA hydrolysis reaction. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no. 4; see also http://www.maik.ru.

[Chemical ribonucleases. 3. Synthesis of organic catalysts of hydrolysis of phosphodiester bonds based on quaternary salts of 1,4-diazabicyclo(2.2.2)octane]. / Khimicheskie ribonukleazy. 3. Sintez organicheskikh katalizatorov gidroliza fosfodiéfirnykh sviazei na osnove chetvertichnykh solei 1,4-diazabitsiklo(2.2.2)oktana.

On the basis of imidazole and bisquaternary salts of 1,4-diazabicyclo[2.2.2]octane, a number of highly effective catalysts of the nDm series (here, n is the number of positive charges at neutral pH values and m is the digital code of the catalytically active fragment: 1, histamine, and 2, histidine methyl ester) were synthesized for the cleavage of the phosphodiester bonds in ribonucleic acids. A general method for the synthesis of chemical ribonucleases was suggested, which helps vary both the number of positive charges in their RNA-binding domain and the catalytic center. By the example of hydrolysis under physiological conditions of the in vitro transcript of tRNA(Lys) from human mitochondria, it was shown that the RNA cleavage rate with the nDm conjugates increases approximately 30-fold along with the increase in the number of positive charges from two to four.