[Chemical ribonucleases. 4. Analysis of the fragment structure of chemical ribonucleases based on 1,4-diazabicyclo[2.2.2]octane].
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.
Konevets
D A
DA
Novosibirsk Institute of Bioorganic Chemistry, Russian Academy of Sciences, Siberian Division, pr. Akademika Lavrent'eva 8, Novosibirsk, 630090 Russia.
Mironova
N L
NL
Bekk
I E
IE
Zenkova
M A
MA
Shishkin
G V
GV
Vlasov
V V
VV
Sil'nikov
V N
VN
D002384:Catalysis; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D009690:Nucleic Acid Conformation; D010879:Piperazines / Q000737:chemistry*; D012349:RNA, Transfer, Asp / Q000737:chemistry; D012357:RNA, Transfer, Lys / Q000737:chemistry; D012260:Ribonucleases / Q000138:chemical synthesis*; D015003:Yeasts / Q000737:chemistry
D010879:Piperazines; D012349:RNA, Transfer, Asp; D012357:RNA, Transfer, Lys; D012260:Ribonucleases; C007306:triethylenediamine