Design and Synthesis of Artificial Ribonucleases Based on 1,4-Diazabicyclo[2.2.2]octane and Imidazole
Обзор
| Общее |
Язык:
Английский,
Жанр:
Обзор (Review),
Статус опубликования:
Опубликована,
Оригинальность:
Переводная
|
| Журнал |
Russian Chemical Bulletin
ISSN: 1066-5285
, E-ISSN: 1573-9171
|
| Вых. Данные |
Год: 2002,
Том: 51,
Номер: 7,
Страницы: 1100-1111
Страниц
: 12
DOI:
10.1023/A:1020937505019
|
| Ключевые слова |
Artificial ribonucleases, Catalysis, RNA hydrolysis, Simulation of enzyme catalytic sites |
| Авторы |
Konevetz D.A.
1
,
Beck I.E.
2
,
Shishkin G.V.
1
,
Vlassov V.V.
1
,
Silnikov V.N.
1
|
| Организации |
| 1 |
Novosibirsk Institute of Bioorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 8 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation
|
| 2 |
G. K. Boreskov Institute of Catalysis, Siberian Branch of the Russian Academy of Sciences, 5 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation
|
|
Информация о финансировании (6)
|
1
|
Civilian Research and Development Foundation
|
REC-008
|
|
2
|
Российский фонд фундаментальных исследований
|
00-15-97969
|
|
3
|
Российский фонд фундаментальных исследований
|
99-04-49538
|
|
4
|
Президиум СО РАН
|
|
|
5
|
Министерство образования и науки Российской Федерации
|
2000.5.91
|
|
6
|
Wellcome Trust
|
063630
|
The review surveys the results of our studies devoted to the design of highly efficient catalysts of hydrolysis of the phosphodiester bonds in RNA. These catalysts contain the imidazole residue in the catalytic domain, one or several bis-quaternized rings of 1,4-diazabicyclo[2.2.2]octane as a polycationic RNA-binding domain, and a lipophilic radical. A versatile approach to artificial ribonucleases of this type was proposed, which allows one to vary not only the number of positive charges in the RNA-binding domain, the structure of the catalytic site, and their mutual arrangement but also the domain structure of the molecule as a whole. Analysis of the catalytic properties of the synthesized constructs makes it possible to optimize the domain structure and the geometry of the molecule ensuring its maximum ribonuclease activity.