Synthesis of novel C4-linked C2-imidazole ribonucleoside phosphoramidite and its application to probing the catalytic mechanism of a ribozyme.
J Org Chem
; 74(6): 2350-6, 2009 Mar 20.
Article
em En
| MEDLINE
| ID: mdl-19220046
ABSTRACT
The synthesis of a novel C4-linked C2-imidazole ribonucleoside phosphoramidite (ICN-C2-PA 1) with a two-carbon linker between imidazole and ribose moieties is described. In the phosphoramidite, POM and 2-cyanoethyl groups were selected to protect the endocyclic amine function of imidazole and the 2'-hydroxyl function of D-ribose, respectively. The C2-imidazole nucleoside, a flexible structural mimic of a purine nucleobase, was successfully incorporated using ICN-C2-PA 1 into position 638 of the VS ribozyme through 2'-TBDMS chemistry to study the role of G638 in general acid-base catalysis. The modified VS ribozyme (G638C2Imz) exhibited significantly greater catalytic activity than observed with the C0-imidazole that has no carbon atoms linking the ribose and the C4-imidazole. Imidazole nucleoside analogues with variable spacer lengths could provide a valuable general methodology for exploring the catalytic mechanisms of ribozymes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organofosforados
/
Ribonucleosídeos
/
RNA Catalítico
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão