Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes

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...

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Autores principales:	Robaldo, L., Izzo, F., Dellafiore, M., Proietti, C., Elizalde, P.V., Montserrat, J.M., Iribarren, A.M.
Formato:	JOUR
Materias:	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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_09680896_v20_n8_p2581_Robaldo
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_09680896_v20_n8_p2581_Robaldo
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spelling	todo:paper_09680896_v20_n8_p2581_Robaldo2023-10-03T15:55:15Z Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes Robaldo, L. Izzo, F. Dellafiore, M. Proietti, C. Elizalde, P.V. Montserrat, J.M. Iribarren, A.M. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09680896_v20_n8_p2581_Robaldo
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Robaldo, L. Izzo, F. Dellafiore, M. Proietti, C. Elizalde, P.V. Montserrat, J.M. Iribarren, A.M. Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes
topic_facet	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
description	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.
format	JOUR
author	Robaldo, L. Izzo, F. Dellafiore, M. Proietti, C. Elizalde, P.V. Montserrat, J.M. Iribarren, A.M.
author_facet	Robaldo, L. Izzo, F. Dellafiore, M. Proietti, C. Elizalde, P.V. Montserrat, J.M. Iribarren, A.M.
author_sort	Robaldo, L.
title	Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes
title_short	Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes
title_full	Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes
title_fullStr	Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes
title_full_unstemmed	Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes
title_sort	influence of conformationally restricted pyrimidines on the activity of 10-23 dnazymes
url	http://hdl.handle.net/20.500.12110/paper_09680896_v20_n8_p2581_Robaldo
work_keys_str_mv	AT robaldol influenceofconformationallyrestrictedpyrimidinesontheactivityof1023dnazymes AT izzof influenceofconformationallyrestrictedpyrimidinesontheactivityof1023dnazymes AT dellafiorem influenceofconformationallyrestrictedpyrimidinesontheactivityof1023dnazymes AT proiettic influenceofconformationallyrestrictedpyrimidinesontheactivityof1023dnazymes AT elizaldepv influenceofconformationallyrestrictedpyrimidinesontheactivityof1023dnazymes AT montserratjm influenceofconformationallyrestrictedpyrimidinesontheactivityof1023dnazymes AT iribarrenam influenceofconformationallyrestrictedpyrimidinesontheactivityof1023dnazymes
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Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes

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