Synthesis of Oligonucleotides Containing 2'-Difluorophosphonylated Thioether Adenosine Derivatives and Study of Their
Aurore Ceuninck1, Maxime Lefeuvre1, Robin Fournier2
1ENSICAEN, Université Caen Normandie, Université de Rouen Normandie, INSA Rouen Normandie, CNRS, Institut CARMeN UMR 6064, 14050 Caen, France.
Abstract:
Efficient introduction of a difluorophosphonylated allyl or propyl thioether onto the 2'-position of adenosine is described. Following the preparation of phosphoramidites derived from these compounds, oligonucleotides incorporating these new chemical modifications were prepared successfully using a 12-mer model sequence. UV-melting experiments revealed a significant decrease in the thermal stability of modified RNA/RNA duplexes. In contrast, enzymatic degradation studies showed that the difluoromethylphosphonate group slows down enzymatic degradation while simultaneously increasing lipophilicity.
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