Synthesis and Properties of Isobicyclo‐DNA

Abstract

Abstract:We present the synthesis of the iso-bicyclo DNA building blocks with the nucleobases A, C, G and T, as well as biophysical and biological properties of oligonucleotides derived thereof. The synthesis of the sugar part was achieved in 5 steps starting from a known intermediate of the tricyclo-DNA synthesis. Dodecamers containing single iso-bicyclo thymidine incorporations, fully modified A-and T-containing sequences and fully modified oligonucleotides containing all four bases were synthesized and characterized. Iso-bicyclo DNA forms stable duplexes with natural nucleic acids with a pronounced preference for DNA over RNA as complements. The most stable duplexes, however, arise by self-pairing. Iso-bicyclo DNA forms preferentially B-DNA-like duplexes with DNA and A-like duplexes with complementary RNA as determined by CD-spectroscopy. Self-paired duplexesshow a yet unknown structure, as judged from CD-spectroscopy. Biochemical tests revealed that isobicyclo DNA is stable in fetal bovine serum and does not elicit RNase H activity.

Building blocks for recognition-encoded oligoesters that form H-bonded duplexes

“…It is clear that duplex formation is not restricted to the precise molecular structure found in DNA and RNA. A range of nucleic acid analogues have been prepared in which the phosphate diester,9–11 the bases,7,12–15 and the sugar have been replaced,16–22 and all of these oligomers form stable duplexes. Synthetic oligomers that bear no relation to nucleic acids have also been shown to form duplexes through various non-covalent interactions: metal–ligand coordination,23,24 salt bridges,25,26 aromatic interactions,27 and hydrogen bonding 28–30.…”

Generation of long, fully modified, and serum-resistant oligonucleotides by rolling circle amplification

“…Serum stability assays 55 The RCA products were generated as described above. The resulting reaction mixtures were heat deactivated (95 °C, 10 min).…”

Sequence-selective duplex formation and template effect in recognition-encoded oligoanilines

“…1 Currently only nucleic acids possess these properties, hence the rst approaches to synthetic sequence-controlled molecules were based on nucleic acids analogues. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Cycles of templated polymerization and selection were used to evolve functional sequences of nucleic acid with recognition or catalytic properties. [20][21][22][23][24][25] Synthetic recognition-encoded oligomers have the potential to display similar properties, which would open the way for directed evolution of function in synthetic polymers.…”