Double-Headed Nucleotides with Arabino Configuration: Synthesis and Hybridization Properties

The formation of new nucleic acid motifs by using double-headed nucleotides is reported. Modified phosphoramidites carrying additional thymine or adenine attached to the 2'-position of arabinouridine through a methylene linker are conveniently prepared and incorporated into oligonucleotides to obtain the modified nucleotide monomers (a)U-T and U-a(A), respectively. The extension of a DNA double helix by one or two additional A:T base pairs is achieved by placing these modified monomers in the opposite strands in a so-called (+1)-zipper arrangement. Hence, 12 basepairs can be presented in an 11-mer or even a 10-mer duplex. The modified nucleotide monomers also behave as dinucleotides when base-paired with two complementary nucleotides from the opposite strand. A new nucleic acid motif is introduced when two (a)UA monomers recognize each other in the center of a duplex.