[Chemical ribonucleases. 2. Design and hydrolytic properties RNase mimetics based on diazabicyclo[2.2.2]octane with various positive charges].
A procedure was proposed allowing one to synthesize RNA mimics on the basis of conjugates of diazabicyclo[2.2.2]octane with imidazole bearing a varying number of positive charges (nDm series, where n is the number of positive charges at neutral pH, m is the code of an imidazole-containing fragment of the catalytic domain: 1, histamine; 2, histidine methyl ester). The hydrolytic activity of six compounds of this series was studied under physiological conditions using in vitro transcript of human mitochondrial tRNA(Lys) as a substrate. It was shown that the rate of RNA hydrolysis with nDm conjugates rises with an increase in the number of positive charges: an approximately 30-fold acceleration of hydrolysis was observed with an increase in the total charge of the construct from +2 to +4.
Zenkova
M A
MA
Novosibirsk Institute of Bioorganic Chemistry, Siberian Division, Russian Academy of Sciences, Novosibirsk, Russia. marzen@niboch.nsc.ru
Vlasov
A V
AV
Konevets
D A
DA
Sil'nikov
V N
VN
Giege
R
R
Vlasov
V V
VV
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D002414:Cations, Monovalent / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D006868:Hydrolysis; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D008274:Magnesium / Q000737:chemistry; D008928:Mitochondria / Q000737:chemistry; D018716:Molecular Mimicry; D017354:Point Mutation; D012357:RNA, Transfer, Lys / Q000737:chemistry / Q000235:genetics; D012260:Ribonucleases / Q000737:chemistry*; D013329:Structure-Activity Relationship
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002414:Cations, Monovalent; D007093:Imidazoles; D012357:RNA, Transfer, Lys; D012260:Ribonucleases; D008274:Magnesium