Synthesis and Thermodynamic and Biophysical Properties of Tricyclo-DNA

Steffens, R.; Leumann, Christian (1999). Synthesis and Thermodynamic and Biophysical Properties of Tricyclo-DNA. Journal of the American Chemical Society, 121(14), pp. 3249-3255. American Chemical Society 10.1021/ja983570w

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The DNA analogue tricyclo-DNA, built from conformationally rigid nucleoside analogues that were linked via tertiary phosphodiester functions, can efficiently be synthesized from the corresponding phosphoramidites by conventional solid-phase cyanoethyl phosphoramidite chemistry. 5'-End phosphorylated tricyclo-DNA sequences are chemically stable in aqueous, pH-neutral media at temperatures from 0 to 90 C. Tricyclo-DNA sequences resist enzymatic hydrolysis by the 3'-exonuclease snake venom phosphodiesterase. Homobasic adenine- and thymine-containing tricyclo-DNA octa- and nonamers are extraordinarily stable A-T base-pairing systems, not only in their own series but also with complementary DNA and RNA. Base mismatch formation is strongly destabilized. As in bicyclo-DNA, the tricyclo-DNA purine sequences preferentially accept a complementary strand on the Hoogsteen face of the base. A thermodynamic analysis reveals entropic benefits in the case of hetero-backbone duplex formation (tricyclo-DNA/DNA duplexes) and both an enthalpic and entropic benefit for duplex formation in the pure tricyclo-DNA series compared to natural DNA. Stability of tricyclo-DNA duplex formation depends more strongly on monovalent salt concentration compared to natural DNA. Homopyrimidine DNA sequences containing tricyclothymidine residues form triplexes with complementary double-stranded DNA. Triple-helix stability depends on the sequence composition and can be higher when compared to that of natural DNA. The use of one tricyclothymidine residue in the center of the self-complementary dodecamer duplex (d(CGCGAAT t CGCG), t = tricyclothymidine) strongly stabilizes its monomolecular hairpin loop structure relative to that of the corresponding pure DNA dodecamer ( T m = +20 C), indicating (tetra)loop-stabilizing properties of this rigid nucleoside analogue.

Item Type:

Journal Article (Original Article)


08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Leumann, Christian


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




American Chemical Society




Christian Leumann

Date Deposited:

20 May 2015 10:44

Last Modified:

05 Dec 2022 14:47

Publisher DOI:


Uncontrolled Keywords:

adenine analogue analogues analysis base Base Pairing Bicyclo-DNA chemistry DNA duplex DUPLEXES hairpin Hoogsteen hydrolysis Mismatch mismatches nucleoside nucleoside analogues phosphoramidite properties purine RNA salt solid phase stability Structure synthesis Temperature thermodynamic triple helix Triplex




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