کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10585481 | 981367 | 2012 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
The catalytic core of a 10-23 DNAzyme was modified introducing conformationally restricted nucleosides such as (2â²R)-, (2â²S)-2â²-deoxy-2â²-C-methyluridine, (2â²R)-, (2â²S)-2â²-deoxy-2â²-C-methylcytidine, 2,2â²-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 2â²-deoxy-2â²-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 2â²-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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 8, 15 April 2012, Pages 2581-2586
Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 8, 15 April 2012, Pages 2581-2586
نویسندگان
Laura Robaldo, Franco Izzo, MarÃa Dellafiore, Cecilia Proietti, Patricia V. Elizalde, Javier M. Montserrat, Adolfo M. Iribarren,