Synthesis and Properties of 6′-Fluoro-tricyclo-DNA

Medvecky, Michal; Istrate, Alena; Leumann, Christian (2015). Synthesis and Properties of 6′-Fluoro-tricyclo-DNA. The Journal of organic chemistry, 80(7), pp. 3556-3565. American Chemical Society 10.1021/acs.joc.5b00184

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The synthesis of the two fluorinated tricyclic nucleosides 6?-F-tc-T and 6?-F-tc-5MeC, as well as the corresponding building blocks for oligonucleotide assembly, was accomplished. An X-ray analysis of N4-benzoylated 6?-F-tc-5MeC 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 ?Tm/mod values of +4.5 °C for 6?-F-tc-5MeC 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Medvecky, Michal; Istrate, Alena and Leumann, Christian

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

1520-6904

Publisher:

American Chemical Society

Language:

English

Submitter:

Christian Leumann

Date Deposited:

01 May 2015 11:37

Last Modified:

14 Mar 2016 02:30

Publisher DOI:

10.1021/acs.joc.5b00184

BORIS DOI:

10.7892/boris.67758

URI:

https://boris.unibe.ch/id/eprint/67758

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