Oligonucleotides composed of a phosphorylated d-altritol backbone with nucleobases introduced in the 2'-position, hybridise strongly and sequence-selectively with RNA in an antiparallel way. The order of hybridisation strength is: dsANA b ANA:RNA b ANA:DNA. Complexes between ANA and RNA or DNA are more stable than between HNA and natural oligonucleotides. The dsANA hybrid is extremely stable. When compared with an identical dsDNA sequence, the DT m per modification is 10.2 8C for a hexamer. CD spectral analysis indicates that ANA complexes are very similar to the A-form dsRNA duplex. ANA are stable in alkaline medium up to pH 12 and, likewise, are not degraded in human serum.

Powerful pyrene probes: Two kinds of pyrene-labeled oligonucleotides (HNA- and RNA-skeleton probes) were explored. The enhanced fluorescence intensity in the monomer region and the disappearance of aggregate/excimer emission in duplexes has been successfully used to detect the hybridization of oligonucleotides. By covalently attaching pyrene chromophores with different linkers onto altritol nucleotides or ribonucleotides, and by varying the number of these pyrene modified altritol nucleotides and ribonucleotides in HNA (hexitol nucleic acid) and RNA, respectively, we have explored the general applicability of pyrene absorbance and especially fluorescence as a probe to monitor RNA hybridization. The results reveal that the backbone of the probes, the number of pyrene units attached and the nature of the tether can all substantially affect the absorbance and fluorescence properties of the probes both in single strand and double strand form. Moreover, the strength of hybridization is also affected. The disappearance of pyrene aggregate/excimer emission and simultaneous increase in monomer emission intensity of the multipyrene-labeled probes has been successfully used to monitor the hybridization of oligonucleotides, including a hairpin structure. Differences in optical response between the HNA- and RNA-skeleton probes upon hybridization indicate that the interaction of pyrene with the nucleobases in both types of duplexes is different.

A synthetic orthogonal polymer embracing a chiral acyclic-phosphonate backbone [(S)-ZNA] is presented that uniquely adds to the emerging family of xenobiotic nucleic acids (XNAs). (S)-ZNA consists of reiterating six-atom structural units and can be accessed in few synthetic steps from readily available phophonomethylglycerol nucleoside (PMGN) precursors. Comparative thermal stability experiments conducted on homo-and heteroduplexes made of (S)-ZNA are described that evince its high selfhybridization efficiency in contrast to poor binding of natural complements. Although preliminary and not conclusive, circular dichroism data and dynamic modeling computations provide support to a left-handed geometry of double-stranded (S)-ZNA. Nonetheless, PMGN diphosphate monomers were recognized as substrates by Escherichia coli (E. coli) polymerase I as well as being imported into E. coli cells equipped with an algal nucleotide transporter. A further investigation into the in vivo propagation of (S)-ZNA culminated with the demonstration of the first synthetic nucleic acid with an acyclic backbone that can be transliterated to DNA by the E. coli cellular machinery. ASSOCIATED CONTENTThe Supporting Information is available free of charge on the ACS Publications website. Detailed synthesis procedures, characterization information, NMR spectra, supplementary methods, figures, and references (PDF).