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

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. This new modification increases the thermostability of an oligonucleotide duplex compared to using a single mode of constraint alone.