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

Abstract

A constrained tricyclic analogue of α-l-LNA (<b>2</b>), 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, <b>5</b>) indicate that this modification is moderately stabilizing when paired with complementary DNA and RNA, but less stabilizing than both α-l-LNA (<b>2</b>) and α-l-TriNA 1 (<b>4</b>)