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Keywords:

  • antisense agents;
  • conformational restriction;
  • nucleosides;
  • oligonucleotides;
  • structure-based design
Thumbnail image of graphical abstract

Dual conformational restriction: A new, highly constrained modification of the α-L-locked nucleic acid (α-L-LNA) scaffold that locks the sugar furanose ring in an N-type configuration and also restricts rotation around torsion angle γ was synthesized (see scheme). This new modification increases the thermostability of an oligonucleotide duplex compared to using a single mode of constraint alone.