Abstract:
The catalytic core of a 10-23 DNAzyme was modified introducing conformationally restricted nucleosides such as (2′R)-, (2′S)-2′-deoxy-2′-C-methyluridine, (2′R)-, (2′S)-2′-deoxy-2′-C-methylcytidine, 2,2′-anhydrouridine and LNA-C, in one, two or three positions. Catalytic activities under pseudo first order conditions were compared at different Mg 2+ concentrations using a short RNA substrate. At low Mg 2+ concentrations, triple modified DNAzymes with similar kinetic performance to that displayed by the non-modified control were identified. In the search for a partial explanation of the obtained results, in silico studies were carried out in order to explore the conformational behavior of 2′-deoxy-2′-C-methylpyrimidines in the context of a loop structure, suggesting that at least partial flexibility is needed for the maintenance of activity. Finally, the modified 2′-C-methyl DNAzyme activity was tested assessing the inhibition of Stat3 expression and the decrease in cell proliferation using the human breast cancer cell line T47D. © 2012 Published by Elsevier Ltd. All rights reserved.
Registro:
Documento: |
Artículo
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Título: | Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes |
Autor: | Robaldo, L.; Izzo, F.; Dellafiore, M.; Proietti, C.; Elizalde, P.V.; Montserrat, J.M.; Iribarren, A.M. |
Filiación: | INGEBI (CONICET), Vuelta de Obligado 2490-(1428), Buenos Aires, Argentina IBYME, Vuelta de Obligado 2490-(1428), Buenos Aires, Argentina Instituto de Ciencias, Universidad Nacional de Gral. Sarmiento, J.M. Gutierrez 1150c, Los Polvorines, (B1613GSX), Prov. de Bs. As., Argentina Laboratorio de Biotransformaciones, Universidad Nacional de Quilmes, Roque Saenz Peña 352, (1876) Bernal, Prov. de Bs. As., Argentina
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Palabras clave: | 2′-C-Methylnucleosides; Deoxyribozymes; DNA structures; DNAzymes; Modified nucleosides; 2' deoxy 2' c methyl pyrimidine derivative; 2' deoxy 2' c methylcytidine; 2' deoxy 2' c methyluridine; 2' methylcytidine; deoxyribozyme; pyrimidine derivative; short hairpin RNA; STAT3 protein; unclassified drug; article; breast cancer; cancer cell; catalysis; cell proliferation; concentration response; controlled study; enzyme activity; enzyme inhibition; enzyme kinetics; enzyme modification; enzyme stability; enzyme structure; enzyme synthesis; human; human cell; nucleic acid synthesis; protein conformation; protein expression; Antineoplastic Agents; Biocatalysis; Cell Proliferation; DNA, Catalytic; DNA, Single-Stranded; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Enzyme Activation; Humans; Molecular Conformation; Pyrimidines; STAT3 Transcription Factor; Structure-Activity Relationship; Tumor Cells, Cultured |
Año: | 2012
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Volumen: | 20
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Número: | 8
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Página de inicio: | 2581
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Página de fin: | 2586
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DOI: |
http://dx.doi.org/10.1016/j.bmc.2012.02.047 |
Título revista: | Bioorganic and Medicinal Chemistry
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Título revista abreviado: | Bioorg. Med. Chem.
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ISSN: | 09680896
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CODEN: | BMECE
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CAS: | deoxyribozyme, 206668-15-7; Antineoplastic Agents; DNA, Catalytic; DNA, Single-Stranded; Pyrimidines; RNA-cleaving DNA 10-23; STAT3 Transcription Factor; STAT3 protein, human
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09680896_v20_n8_p2581_Robaldo |
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Citas:
---------- APA ----------
Robaldo, L., Izzo, F., Dellafiore, M., Proietti, C., Elizalde, P.V., Montserrat, J.M. & Iribarren, A.M.
(2012)
. Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes. Bioorganic and Medicinal Chemistry, 20(8), 2581-2586.
http://dx.doi.org/10.1016/j.bmc.2012.02.047---------- CHICAGO ----------
Robaldo, L., Izzo, F., Dellafiore, M., Proietti, C., Elizalde, P.V., Montserrat, J.M., et al.
"Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes"
. Bioorganic and Medicinal Chemistry 20, no. 8
(2012) : 2581-2586.
http://dx.doi.org/10.1016/j.bmc.2012.02.047---------- MLA ----------
Robaldo, L., Izzo, F., Dellafiore, M., Proietti, C., Elizalde, P.V., Montserrat, J.M., et al.
"Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes"
. Bioorganic and Medicinal Chemistry, vol. 20, no. 8, 2012, pp. 2581-2586.
http://dx.doi.org/10.1016/j.bmc.2012.02.047---------- VANCOUVER ----------
Robaldo, L., Izzo, F., Dellafiore, M., Proietti, C., Elizalde, P.V., Montserrat, J.M., et al. Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes. Bioorg. Med. Chem. 2012;20(8):2581-2586.
http://dx.doi.org/10.1016/j.bmc.2012.02.047