The synthesis of double-headed nucleosides by the CuAAC reaction and their effect in secondary nucleic acid structures

Abstract

Four double-headed nucleosides were prepared by the CuAAC reaction. Hereby, a triazole-containing linker connects an additional thymine or adenine to the 2′-position of 2′-deoxyuridine, a thymine to the 5′-position of thymidine and a thymine to the 6′-position of an LNA-thymidine monomer. Whereas no conclusive recognition effects of the additional thymines were found when introduced in LNA or at the 5′-position, both thymine and adenine in the 2′-position were found to stabilise three-way junctions in both dsDNA and DNA : RNA contexts and to give cross-strand interactions in a DNA-duplex, when specifically introduced in a so-called (+1)-zipper motif.