Not All 2',4'-Bridged Modifications Stabilize DNA/RNA Duplexes.

2',4'-Bridged modifications such as 2'-O,4'-C-methylene-bridged nucleotides (LNAs) and 2'-O,4'-C-ethylene-bridged nucleotides (ENAs) provide high binding affinity for duplex formation. Stabilization by the introduction of the bridged nucleic acids is considered to be due to pre-organization. In this study, we found that the introduction of 2',4'-C-bridged 2'-deoxynucleotides (CRNs; Conformationally Restricted Nucleotides) into DNA/RNA duplexes leads to destabilization, as opposed to the previously accepted notion that 2',4'-bridged modifications always lead to stabilization.