Chemical Ribonucleases: 4.1 An Analysis of the Domain Structure of Chemical Ribonucleases Based
on 1,4-Diazabicyclo[2.2.2]octane
Full article
| Общее |
Language:
Английский,
Genre:
Full article,
Status:
Published,
Source type:
Translated
|
| Journal |
Russian Journal of Bioorganic Chemistry
ISSN: 1068-1620
, E-ISSN: 1608-330X
|
| Output data |
Year: 2002,
Volume: 28,
Number: 4,
Pages: 331-341
Pages count
: 11
DOI:
10.1023/A:1019504227151
|
| Tags |
Artificial ribonucleases, Domain structure, RNA, hydrolysis |
| Authors |
Konevetz D.A.
1
,
Mironova N.L.
2
,
Beck I.E.
3
,
Zenkova M.A.
1
,
Shishkin G.V.
1
,
Vlassov V.V.
1
,
Silnikov V.N.
1
|
| Affiliations |
| 1 |
Novosibirsk Institute of Bioorganic Chemistry, Russian Academy of Sciences, Siberian Branch, pr. Akademika Lavrent’eva 8, Novosibirsk, 630090 Russia
|
| 2 |
Novosibirsk State University, ul. Pirogova 2, Novosibirsk, 630090 Russia
|
| 3 |
Boreskov Institute of Catalysis, Russian Academy of Sciences, Siberian Branch, pr. Akademika Lavrent’eva 5, Novosibirsk, 630090 Russia
|
|
Funding (5)
|
1
|
Russian Foundation for Basic Research
|
00-15-97969
|
|
2
|
Russian Foundation for Basic Research
|
99-04-49538
|
|
3
|
Wellcome Trust
|
063630
|
|
4
|
The Ministry of Education and Science of the Russian Federation
|
|
|
5
|
Президиум РАН
|
219
|
Artificial ribonucleases of the ABLkCm series were synthesized. They consist of a lipophilic alkyl
radical (Et, n-C14H29, or n-C15H31) Ä, an “RNA-binding domain” Ç (bisquaternary salt of 1,4-diazabicyclo[2.2.2]octane), a “catalytic domain” ëm [histamine (ë1) or histidine (ë3) 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 tRNALys and
yeast tRNAAsp 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°ë). 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 domains. The results indicate an important role of hydrophobic interactions in the acceleration of the RNA hydrolysis reaction.