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    Isoguanine and 5-Methyl-Isocytosine bases, in vitro and in vivo

    Bande, O. and Abu El Asrar, R. and Braddick, D. and Dumbre, S. and Pezo, V. and Schepers, G. and Pinheiro, Vitor B. and Lescrinier, E. and Holliger, P. and Marlière, P. and Herdewijn, P. (2015) Isoguanine and 5-Methyl-Isocytosine bases, in vitro and in vivo. Chemistry: A European Journal 21 (13), pp. 5009-5022. ISSN 0947-6539.

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    The synthesis, base-pairing properties and in vitro and in vivo characteristics of 5-methyl-isocytosine (isoCMe) and isoguanine (isoG) nucleosides, incorporated in an HNA(h) (hexitol nucleic acid)–DNA(d) mosaic backbone, are described. The required h-isoG phosphoramidite was prepared by a selective deamination as a key step. As demonstrated by Tm measurements the hexitol sugar showed slightly better mismatch discrimination against dT. The disoG base mispairing follows the order T>G>C while the hisoG base mispairing follows the order G>C>T. The h- and d-isoCMe bases mainly mispair with G. Enzymatic incorporation experiments show that the hexitol backbone has a variable effect on selectivity. In the enzymatic assays, isoG misincorporates mainly with T, and isoCMe misincorporates mainly with A. Further analysis in vivo confirmed the patterns of base-pair interpretation for the deoxyribose and hexitol isoCMe/isoG bases in a cellular context, through incorporation of the bases into plasmidic DNA. Results in vivo demonstrated that mispairing and misincorporation was dependent on the backbone scaffold of the base, which indicates rational advances towards orthogonality.


    Item Type: Article
    Keyword(s) / Subject(s): HNA, isoG, polymerase, nucleosides, XNA plasmid
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Research Centres and Institutes: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Vitor Bernardes pinheiro
    Date Deposited: 17 Jun 2015 12:34
    Last Modified: 02 Aug 2023 17:17


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