- Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes
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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 Mg2+ concentrations using a short RNA substrate. At low Mg2+ 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.
- Robaldo, Laura,Izzo, Franco,Dellafiore, María,Proietti, Cecilia,Elizalde, Patricia V.,Montserrat, Javier M.,Iribarren, Adolfo M.
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p. 2581 - 2586
(2012/06/16)
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- Synthesis of the phosphoramidite derivative of 2′-deoxy-2′-C-β-methylcytidine
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2′-Deoxy-2′-C-β-methylnucleosides elicit interest as potential therapeutic agents and as analogues for the analysis of nucleic acid structure and function. An efficient route for the synthesis of 2′-deoxy-2′-C-methyluridine (11), 2′-deoxy-2′-C-methylcytidine (12), and the phosphoramidite derivative of 2′-deoxy-2′-C-β-methylcytidine (10, 46% overall yield) from 1,2,3,5-tetra-O-benzoyl-2-C-β-methylribofuranose (1) is described.
- Li, Nan-Sheng,Piccirilli, Joseph A.
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p. 6799 - 6802
(2007/10/03)
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