Abstract:
We propose 2′-C-methylnucleotides as a new class of 2′-modified RNA mimics. These analogues are expected to provide 2′-OH groups capable of reproducing the interactions observed in natural RNA and, due to the presence of the Me group, to possess increased stability towards nucleases. In this work, we investigate the catalytic activity and nucleases resistance of hammerhead ribozymes carrying 2′-C-methyluridines in positions 4 and 7 of the catalytic core. We describe the in vitro activity of this chimeric molecules and their stability in cell lysate, fetal calf serum, and cell culture medium. The data show that, when only position 4 is modified, activity decreases twofold; while, when both 4 and 7 positions are substituted, a sevenfold drop in activity is observed. Regarding biological stability, the main increase of the half-life time is observed when position 7 is modified. These results suggest that 2′-C-methylnucleotides may be useful in the design of chemically synthesized RNA mimics with biological activity. © 2005 Verlag Helvetica Chimica Acta AG, Zürich.
Registro:
Documento: |
Artículo
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Título: | Activity and stability of hammerhead ribozymes containing 2′-C-methyluridine: A new RNA mimic |
Autor: | Gallo, M.; Far, R.K.-K.; Sczakiel, G.; Iribarren, A.M. |
Filiación: | Lab. NMR di Biostrutture/Biosistemi, Univ. Studi di Roma Tor Vergata, Via della Ricerca Scientifica 1, I-00133 Rome, Italy Dipartimento di Molecular Medicine, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany Universidad Nacional de Quilmes, Roque Sáenz Peña 180, Bernal 1876 Pcia. de Buenos Aires, Argentina Inst. de Invest. Ingenieria Genetica, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
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Palabras clave: | hammerhead ribozyme; hydroxyl group; methyl group; RNA; RNA derivative; uridine derivative; article; catalysis; cell lysate; chimera; controlled study; culture medium; drug activity; drug design; enzyme active site; enzyme activity; enzyme modification; enzyme stability; enzyme structure; fetal calf serum; half life time; human; human cell; in vitro study; molecular interaction; substitution reaction; Biomimetic Materials; Molecular Mimicry; RNA, Catalytic; Uridine |
Año: | 2005
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Volumen: | 2
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Número: | 2
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Página de inicio: | 198
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Página de fin: | 204
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DOI: |
http://dx.doi.org/10.1002/cbdv.200590002 |
Título revista: | Chemistry and Biodiversity
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Título revista abreviado: | Chem. Biodiversity
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ISSN: | 16121872
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CAS: | RNA, 63231-63-0; 2'-C-methyluridine; RNA, Catalytic; Uridine, 58-96-8; hammerhead ribozyme
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_16121872_v2_n2_p198_Gallo |
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Citas:
---------- APA ----------
Gallo, M., Far, R.K.-K., Sczakiel, G. & Iribarren, A.M.
(2005)
. Activity and stability of hammerhead ribozymes containing 2′-C-methyluridine: A new RNA mimic. Chemistry and Biodiversity, 2(2), 198-204.
http://dx.doi.org/10.1002/cbdv.200590002---------- CHICAGO ----------
Gallo, M., Far, R.K.-K., Sczakiel, G., Iribarren, A.M.
"Activity and stability of hammerhead ribozymes containing 2′-C-methyluridine: A new RNA mimic"
. Chemistry and Biodiversity 2, no. 2
(2005) : 198-204.
http://dx.doi.org/10.1002/cbdv.200590002---------- MLA ----------
Gallo, M., Far, R.K.-K., Sczakiel, G., Iribarren, A.M.
"Activity and stability of hammerhead ribozymes containing 2′-C-methyluridine: A new RNA mimic"
. Chemistry and Biodiversity, vol. 2, no. 2, 2005, pp. 198-204.
http://dx.doi.org/10.1002/cbdv.200590002---------- VANCOUVER ----------
Gallo, M., Far, R.K.-K., Sczakiel, G., Iribarren, A.M. Activity and stability of hammerhead ribozymes containing 2′-C-methyluridine: A new RNA mimic. Chem. Biodiversity. 2005;2(2):198-204.
http://dx.doi.org/10.1002/cbdv.200590002