Article Dans Une Revue Chemistry - A European Journal Année : 2015

Isoguanine and 5‐Methyl‐Isocytosine Bases, In Vitro and In Vivo

Omprakash Bande
Rania Abu El Asrar
  • Fonction : Auteur
Darren Braddick
  • Fonction : Auteur
Shrinivas Dumbre
  • Fonction : Auteur
Valérie Pezo
Guy Schepers
  • Fonction : Auteur
Vitor Pinheiro
  • Fonction : Auteur
Eveline Lescrinier
  • Fonction : Auteur
Philipp Holliger
  • Fonction : Auteur
Philippe Marlière
Piet Herdewijn

Résumé

Abstract The synthesis, base‐pairing properties and in vitro and in vivo characteristics of 5‐methyl‐isocytosine (isoC Me ) 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 T m measurements the hexitol sugar showed slightly better mismatch discrimination against dT. The d‐isoG base mispairing follows the order T>G>C while the h‐isoG base mispairing follows the order G>C>T. The h‐ and d‐isoC Me 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 isoC Me misincorporates mainly with A. Further analysis in vivo confirmed the patterns of base‐pair interpretation for the deoxyribose and hexitol isoC Me /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.

Dates et versions

hal-04356536 , version 1 (20-12-2023)

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Citer

Omprakash Bande, Rania Abu El Asrar, Darren Braddick, Shrinivas Dumbre, Valérie Pezo, et al.. Isoguanine and 5‐Methyl‐Isocytosine Bases, In Vitro and In Vivo. Chemistry - A European Journal, 2015, 21 (13), pp.5009-5022. ⟨10.1002/chem.201406392⟩. ⟨hal-04356536⟩
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