We describe a rational approach devoted to modulate the sugar-phosphate backbone geometry of nucleic acids. Constraints were generated by connecting one oxygen of the phosphate group to a carbon of the sugar moiety. The so-called dioxaphosphorinane rings were introduced at key positions along the sugar-phosphate backbone allowing the control of the six-torsion angles to ζ defining the polymer structure. The syntheses of all the members of the D-CNA family are described, and we emphasize the effect on secondary structure stabilization of a couple of diastereoisomers of , -D-CNA exhibiting wether B-type canonical values or not. 1. Introduction It is now clear that nucleic acids play several different roles in the living cell from genetic code storage to the catalysis of chemical reactions in ribosome. All of these particular behaviours are associated with various and very often transient structures of these polymers. The most prevalent secondary structure of nucleic acids is the double helix that can adopt either A- or B-type depending on the hydration level and/or the 2′-deoxyribosyl or ribosyl nature of the hybridized strands. While the backbone organization of double-stranded DNA and RNA is normally quite regular, there are many other secondary and tertiary structures that DNA and RNA molecules can adopt in vivo [1]. It is also well established that these disparate structures, which are predisposed to promote a significant local conformational heterogeneity in the sugar-phosphate backbone, play a crucial role in the fundamental biological processes where protein-nucleic acid interactions, folding, or catalytic activity are involved [2]. As a consequence nucleic acids can fold into biologically relevant distinct structures such as bulges, hairpin loops, U-turns, adenosine platforms, branched junctions, or quadruplexes (Figure 1). As proposed by few studies, the sugar/phosphate backbone of these unusual motifs exhibit a variety of conformations, which markedly differ from the regular conformational states of duplex DNA and RNA molecules [3–8]. However, the intrinsic role imparted to the phosphate diester backbone in respect with bases sequence in stamping these structures is still not properly defined. Figure 1: Examples of DNA secondary structures and associated backbone-torsion angles γ/ β/ α/ ε/ ζ of representative dinucleotide units. The following 6-fold staggered pattern of the torsional angles is used: cis = ° (c), gauche(+) = ° (g +), anticlinal(+) = ° (a +), trans = ° ( ), anticlinal(？) = ° (a ？), and gauche(？) = ° (g ？). The notation g ？/a ？ is
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