The replacement of the furanose moiety of DNA by a cyclohexene ring gives a new nucleic acid structure: cyclohexene nucleic acids or CeNA. CeNAs can be obtained by the classical phosphoramidite ...chemisty starting from protected cyclohexenyl nucleoside building blocks. Incorporation of cylcohexenyl nucleosides in a DNA chain increases the stability of a DNA/RNA hybrid. The complex formed between cyclohexenyl oligoadenylate and its DNA or RNA complement is of similar stability. Circular dichroism (CD) and NMR studies indicate easy conformational adaptation of a cyclohexenyl nucleoside when incorporated in a natural nucleic acid structure. CeNA is stable against degradation in serum and a CeNA/RNA hybrid is able to activate E. Coli RNase H, resulting in cleavage of the RNA strand.
Cross‐talking between nucleic acids is a prerequisite for information transfer. The absence of observed base pairing interactions between pyranose and furanose nucleic acids has excluded considering ...the former type as a (potential) direct precursor of contemporary RNA and DNA. We observed that α‐pyranose oligonucleotides (α‐homo‐DNA) are able to hybridize with RNA and that both nucleic acid strands are parallel oriented. Hybrids between α‐homo‐DNA and DNA are less stable. During the synthesis of α‐homo‐DNA we observed extensive conversion of N 6‐benzoyl‐5‐methylcytosine into thymine under the usual deprotection conditions of oligonucleotide synthesis. α‐Homo‐DNA:RNA represents the first hybridization system between pyranose and furanose nucleic acids. The duplex formed between α‐homo‐DNA and RNA was investigated using CD, NMR spectroscopy, and molecular modeling. The general rule that orthogonal orientation of base pairs prevents hybridization is infringed. NMR experiments demonstrate that the base moieties of α‐homo‐DNA in its complex with RNA, are equatorially oriented and that the base moieties of the parallel RNA strand are pseudoaxially oriented. Modeling experiments demonstrate that the duplex formed is different from the classical A‐ or B‐type double stranded DNA. We observed 15 base pairs in a full helical turn. The average interphosphate distance in the RNA strand is 6.2 Å and in the α‐homo‐DNA strand is 6.9 Å. The interstrand P−P distance is much larger than found in the typical A‐ and B‐DNA. Most helical parameters are different from those of natural duplexes.
Cross‐talking between nucleic acids is a prerequisite for information transfer. The synthesis and successful hybridization experiments of α‐pyranose oligonucleotides (α‐homo‐DNA) with RNA (see scheme for a nucleotide pair) to give parallel oriented nucleic acid strands is described.
Cyclohexene nucleic acids (CeNA) were synthesized using classical phosporamidite chemistry. Incorporation of a cyclohexene nucleo-side in a DNA chain leads to an increase in stability of the DNA/RNA ...duplex. CeNA is stable against degradation in serum. A CeNA/RNA hybrid is able to activate E. Coli RNase H, resulting in cleavage of the RNA strand.
PDF
