title: Synthesis and properties of isobicyclo-DNA.
abstract: We present the synthesis of the isobicyclo-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 isobicyclo-thymidine incorporations, fully modified A- and T-containing sequences, and fully modified oligonucleotides containing all four bases were synthesized and characterized. Isobicyclo-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. Isobicyclo-DNA forms preferentially B-DNA-like duplexes with DNA and A-like duplexes with complementary RNA as determined by circular dichroism (CD) spectroscopy. Self-paired duplexes show 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 RNaseH activity.
authors.affiliation: Department of Chemistry & Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.
authors.forename: Anna-Barbara
authors.initials: AB
authors.lastname: Gerber
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Leumann
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D004247:DNA / Q000138:chemical synthesis* / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D012313:RNA / Q000737:chemistry; D016914:Ribonuclease H / Q000378:metabolism
chemical_list: D009841:Oligonucleotides; D012313:RNA; D004247:DNA; D016914:Ribonuclease H