Activity and stability of hammerhead ribozymes containing 2′-C-methyluridine: A new RNA mimic
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, w...
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2005
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_16121872_v2_n2_p198_Gallo http://hdl.handle.net/20.500.12110/paper_16121872_v2_n2_p198_Gallo |
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paper:paper_16121872_v2_n2_p198_Gallo2023-06-08T16:25:12Z Activity and stability of hammerhead ribozymes containing 2′-C-methyluridine: A new RNA mimic 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 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. 2005 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_16121872_v2_n2_p198_Gallo http://hdl.handle.net/20.500.12110/paper_16121872_v2_n2_p198_Gallo |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Activity and stability of hammerhead ribozymes containing 2′-C-methyluridine: A new RNA mimic |
| topic_facet |
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 |
| description |
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. |
| title |
Activity and stability of hammerhead ribozymes containing 2′-C-methyluridine: A new RNA mimic |
| title_short |
Activity and stability of hammerhead ribozymes containing 2′-C-methyluridine: A new RNA mimic |
| title_full |
Activity and stability of hammerhead ribozymes containing 2′-C-methyluridine: A new RNA mimic |
| title_fullStr |
Activity and stability of hammerhead ribozymes containing 2′-C-methyluridine: A new RNA mimic |
| title_full_unstemmed |
Activity and stability of hammerhead ribozymes containing 2′-C-methyluridine: A new RNA mimic |
| title_sort |
activity and stability of hammerhead ribozymes containing 2′-c-methyluridine: a new rna mimic |
| publishDate |
2005 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_16121872_v2_n2_p198_Gallo http://hdl.handle.net/20.500.12110/paper_16121872_v2_n2_p198_Gallo |
| _version_ |
1768544703189352448 |