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On the enzymatic formation of metal base pairs with thiolated and pKa-perturbed nucleotides

Abstract : The formation of artificial metal base pairs is an alluring and versatile method for the functionalization of nucleic acids. Access to DNA functionalized with metal base pairs is granted mainly by solid-phase synthesis. An alternative, yet underexplored method, envisions the installation of metal base pairs via the polymerization of modified nucleoside triphosphates. Herein, we have explored the possibility of using thiolated and pKa-perturbed nucleotides for the enzymatic construction of artificial metal base pairs. The thiolated nucleotides S2C, S6G, and S4T as well as the fluorinated analog 5FU are readily incorporated opposite a templating S4T nucleotide through the guidance of metal cations. Multiple incorporation of the modified nucleotides along with polymerase bypass of the unnatural base pairs are also possible under certain conditions. The thiolated nucleotides S4T, S4T, S2C, and S6G were also shown to be compatible with the synthesis of modified, high molecular weight ssDNA products through TdT-mediated tailing reactions. Thus, sulfur-substitution and pKa perturbation represent alternative strategies for the design of modified nucleotides compatible with the enzymatic construction of metal base pairs.
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Submitted on : Friday, July 19, 2019 - 12:20:26 PM
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Fabienne Levi-Acobas, Pascal Röthlisberger, Ivo Sarac, Philippe Marlière, Piet Herdewyn, et al.. On the enzymatic formation of metal base pairs with thiolated and pKa-perturbed nucleotides. ChemBioChem, Wiley-VCH Verlag, 2019, ⟨10.1002/cbic.201900399⟩. ⟨pasteur-02185141⟩

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