Unnatural nucleosides have been explored to expand the properties and the applications of oligonucleotides. This paper briefly summarizes nucleic acid analogs in which the base is modified or replaced by an unnatural stacking group for the study of nucleic acid interactions. We also describe the nucleoside analogs of a base pair-mimic structure that we have examined. Although the base pair-mimic nucleosides possess a simplified stacking moiety of a phenyl or naphthyl group, they can be used as a structural analog of Watson-Crick base pairs. Remarkably, they can adopt two different conformations responding to their interaction energies, and one of them is the stacking conformation of the nonpolar aromatic group causing the site-selective flipping of the opposite base in a DNA double helix. The base pair-mimic nucleosides can be used to study the mechanism responsible for the base stacking and the flipping of bases out of a nucleic acid duplex. 1. Introduction Nucleic acids have many remarkable properties that other molecules do not possess. The most notable property is the ability of sequence-specific hybridization through Watson-Crick base pairing. Even a short oligonucleotide sequence, readily synthesized chemically and available on the market at a relatively low cost, can self-assemble into a defined structure and hybridize specifically to a target sequence in accordance with the base pair-rule of A/T and G/C. Importantly, the controls of the self-assembly and the hybridization are not difficult when one considers the interaction energy of nucleic acid reactions [1]. Additionally, it is possible to conjugate with other molecules, such as fluorescent dyes, amino acids, and nanoparticles. Thus, the methodologies that utilize DNA and RNA oligonucleotides as a tool for technology such as nanomaterial and medicinal and therapeutic usages have become of broader interest over the past decades. The most common structure formed by base pairing is the right-handed double helix. The geometry of Watson-Crick base pairs mediated by hydrogen bonding is similar regardless of the nucleotide sequence, and this allows a double helical conformation virtually identical without disrupting coplanar stacking between adjacent base pairs. Interbase hydrogen bonding is responsible for the association of complementary bases, which is essential for the storage and retrieval of genetic information. Hydrogen donors and acceptors on the purine and pyrimidine bases direct the base pair partner by forming two hydrogen bonds in the A/T pair and three in the C/G pair (Figure 1(a)).
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