title: Synthesis and properties of 6'-fluoro-tricyclo-DNA.
abstract: The synthesis of the two fluorinated tricyclic nucleosides 6'-F-tc-T and 6'-F-tc-5(Me)C, as well as the corresponding building blocks for oligonucleotide assembly, was accomplished. An X-ray analysis of N(4)-benzoylated 6'-F-tc-(5Me)C reavealed a 2'-exo (north) conformation of the furanose ring, characterizing it as an RNA mimic. In contrast to observations in the bicyclo-DNA series, no short contact between the fluorine atom and the H6 of the base, reminiscent of a nonclassical F···H hydrogen bond, could be observed. Tm measurements of modified oligodeoxynucleotides with complementary RNA showed slightly sequence-dependent duplex stabilization profiles with maximum ΔTm/mod values of +4.5 °C for 6'-F-tc-(5Me)C and +1 °C for 6'-F-tc-T. In comparison with parent tc-modified oligonucleotides, no relevant changes in Tm were detected, attributing the fluorine substituent a neutral role in RNA affinity. A structural analysis of duplexes with DNA and RNA by CD-spectroscopy revealed a shift from B- to A-type conformation induced by the 6'-F-tc-nucleosides. This is not a specific "fluorine effect", as the same is also observed for the parent tc-modifications. The two fluorinated tc-nucleosides were also incorporated into a pure tricyclo-DNA backbone and showed no discrimination in Tm with complementary RNA, demonstrating that 6'-F substitution is also compatible within fully modified tc-oligonucleotides.
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland.
authors.forename: Michal
authors.initials: M
authors.lastname: Medvecky
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland.
authors.forename: Alena
authors.initials: A
authors.lastname: Istrate
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Leumann
mesh_terms: D020029:Base Pairing; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004247:DNA / Q000138:chemical synthesis* / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000138:chemical synthesis*; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*
chemical_list: D009705:Nucleosides; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D005461:Fluorine; D012313:RNA; D004247:DNA