A Constrained Tricyclic Nucleic Acid Analogue of α‑l‑LNA: Investigating the Effects of Dual Conformational Restriction on Duplex Thermal Stability

A constrained tricyclic analogue of α-l-LNA (2), which contains dual modes of conformational restriction about the ribose sugar moiety, has been synthesized and characterized by X-ray crystallography. Thermal denaturation experiments of oligonucleotide sequences containing this tricyclic α-l-LNA analogue (α-l-TriNA 2, 5) indicate that this modification is moderately stabilizing when paired with complementary DNA and RNA, but less stabilizing than both α-l-LNA (2) and α-l-TriNA 1 (4).