Abstract
The substrate specificity towards RNA/DNA chimeric oligonucleotide containing stereodefined phosphorothioate bond of the RP and SP configuration at the scissile site was determined for the cleavage reaction catalyzed by the deoxyribozyme 10-23. Single-turnover kinetics in the presence of either Mg2+or Mn2+ was used to determine the thio- and manganese rescue effects of the cleavage reaction. The obtained results indicate that the unmodified substrate and its SP thio-analog are specifically and efficiently cleaved even at low metal ion concentration (0.02 mM). By contrast, the presence of the phosphorothioate bond of the RP configuration at the scissile site caused complete resistance of this substrate in the deoxyribozyme-mediated cleavage reaction in a broad metal ion concentration (from 0.02 to 100 mM). These findings indicate the lack of a direct metal ion coordination to the non-bridging phosphate oxygens of the scissile phosphate bond (no β catalysis is observed). Plausible mechanism of this 10-23 deoxyribozyme-assisted catalysis reaction involves engagement of the divalent metal cation in the coordination of the oxygen of the 2-OH group and migration of proton to the pro-RP oxygen of the scissile phosphate.
Keywords: Phosphorothioate, Scissile Site, Deoxyribozyme 10-23, Cleavage Activity, chimeric oligonucleotide, catalysis reaction
Current Organic Chemistry
Title: Effect of RP and SPPhosphorothioate Substitution at the Scissile Site on the Cleavage Activity of Deoxyribozyme 10-23
Volume: 12 Issue: 12
Author(s): Barbara Nawrot, Kinga Widera, Milena Sobczak, Marzena Wojcik and Wojciech J. Stec
Affiliation:
Keywords: Phosphorothioate, Scissile Site, Deoxyribozyme 10-23, Cleavage Activity, chimeric oligonucleotide, catalysis reaction
Abstract: The substrate specificity towards RNA/DNA chimeric oligonucleotide containing stereodefined phosphorothioate bond of the RP and SP configuration at the scissile site was determined for the cleavage reaction catalyzed by the deoxyribozyme 10-23. Single-turnover kinetics in the presence of either Mg2+or Mn2+ was used to determine the thio- and manganese rescue effects of the cleavage reaction. The obtained results indicate that the unmodified substrate and its SP thio-analog are specifically and efficiently cleaved even at low metal ion concentration (0.02 mM). By contrast, the presence of the phosphorothioate bond of the RP configuration at the scissile site caused complete resistance of this substrate in the deoxyribozyme-mediated cleavage reaction in a broad metal ion concentration (from 0.02 to 100 mM). These findings indicate the lack of a direct metal ion coordination to the non-bridging phosphate oxygens of the scissile phosphate bond (no β catalysis is observed). Plausible mechanism of this 10-23 deoxyribozyme-assisted catalysis reaction involves engagement of the divalent metal cation in the coordination of the oxygen of the 2-OH group and migration of proton to the pro-RP oxygen of the scissile phosphate.
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Cite this article as:
Nawrot Barbara, Widera Kinga, Sobczak Milena, Wojcik Marzena and Stec J. Wojciech, Effect of RP and SPPhosphorothioate Substitution at the Scissile Site on the Cleavage Activity of Deoxyribozyme 10-23, Current Organic Chemistry 2008; 12 (12) . https://dx.doi.org/10.2174/138527208785161204
DOI https://dx.doi.org/10.2174/138527208785161204 |
Print ISSN 1385-2728 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5348 |
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