[Chemical ribonucleases. 3. Synthesis of organic catalysts of hydrolysis of phosphodiester bonds based on quaternary salts of 1,4-diazabicyclo(2.2.2)octane].
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.
Konevets
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DA
Novosibirsk Institute of Bioorganic Chemistry, Siberian Division, Russian Academy of Sciences, prosp. Akademika Lavrent'eva 8, Novosibirsk, 630090 Russia. chek@niboch.nsc.ru
Bekk
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IE
Sil'nikov
V N
VN
Zenkova
M A
MA
Shishkin
G V
GV
D006801:Humans; D006868:Hydrolysis; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D012313:RNA / Q000737:chemistry; D000077278:RNA, Mitochondrial; D012260:Ribonucleases / Q000737:chemistry*; D013329:Structure-Activity Relationship
D007093:Imidazoles; D010879:Piperazines; D000644:Quaternary Ammonium Compounds; D000077278:RNA, Mitochondrial; D012313:RNA; D012260:Ribonucleases; C007306:triethylenediamine