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

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.

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