Structure-Based Design of a Highly Constrained Nucleic Acid Analogue: Improved Duplex Stabilization by Restricting Sugar Pucker and Torsion Angle γ


  • R.D.G. is grateful to NSERC (CGS D) for a postgraduate scholarship. We thank Benoît Deschênes-Simard for X-ray crystallographic analyses.


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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.