Chemical Ribonucleases: 4.1 An Analysis of the Domain Structure of Chemical Ribonucleases Based on 1,4-Diazabicyclo[2.2.2]octane Full article
Journal |
Russian Journal of Bioorganic Chemistry
ISSN: 1068-1620 , E-ISSN: 1608-330X |
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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 |
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Affiliations |
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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 |
Abstract:
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.
Cite:
Konevetz D.A.
, Mironova N.L.
, Beck I.E.
, Zenkova M.A.
, Shishkin G.V.
, Vlassov V.V.
, Silnikov V.N.
Chemical Ribonucleases: 4.1 An Analysis of the Domain Structure of Chemical Ribonucleases Based on 1,4-Diazabicyclo[2.2.2]octane
Russian Journal of Bioorganic Chemistry. 2002. V.28. N4. P.331-341. DOI: 10.1023/A:1019504227151 WOS Scopus РИНЦ
Chemical Ribonucleases: 4.1 An Analysis of the Domain Structure of Chemical Ribonucleases Based on 1,4-Diazabicyclo[2.2.2]octane
Russian Journal of Bioorganic Chemistry. 2002. V.28. N4. P.331-341. DOI: 10.1023/A:1019504227151 WOS Scopus РИНЦ
Original:
Коневец Д.А.
, Миронова Н.Л.
, Бекк И.Э.
, Зенкова М.А.
, Шишкин Г.В.
, Власов В.В.
, Сильников В.Н.
Химические рибонуклеазы. 4. Анализ фрагментной структуры химических рибонуклеаз на основе 1,4-диазабицикло[2.2.2]октана
Биоорганическая химия. 2002. Т.28. №4. С.367-378. Scopus РИНЦ
Химические рибонуклеазы. 4. Анализ фрагментной структуры химических рибонуклеаз на основе 1,4-диазабицикло[2.2.2]октана
Биоорганическая химия. 2002. Т.28. №4. С.367-378. Scopus РИНЦ
Dates:
Submitted: | May 14, 2001 |
Published print: | Jul 1, 2002 |
Identifiers:
Web of science | WOS:000177708000013 |
Scopus | 2-s2.0-0036340955 |
Elibrary | 13400305 |
Chemical Abstracts | 2002:575812 |
Chemical Abstracts (print) | 137:381573 |
OpenAlex | W114462172 |