Two Carbocyclic Locked Nucleic Acid Analogues Give Structural Information about the Role of Hydration in A-Type Duplexes

Abstract

Two locked nucleic acid (LNA) analogues with three-carbon 2′-4′ linkages, saturated or unsaturated, are synthesized using a ring-closing metathesis based strategy. Strongly stabilized duplexes with complementary RNA and slightly destabilized duplexes with complementary DNA are observed. CD-spectroscopy indicates a less pronounced shift toward A-type duplexes compared to LNA. These results combining a strong N-type conformation with the absence of a 2′-oxygen demonstrate a stronger importance of minor groove hydration in an intermediate duplex type than in an A-type duplex.

Keywords:

• Locked nucleic acid
• RNA recognition
• duplex hydration

The Danish National Research Foundation, the Danish Natural Research Council, and the Danish Centre for Scientific Computing are thanked for financial support.