Synthesis and Biochemical Characterization of Tricyclothymidine Triphosphate (tc-TTP)

Hollenstein, Marcel; Leumann, Christian (2014). Synthesis and Biochemical Characterization of Tricyclothymidine Triphosphate (tc-TTP). ChemBioChem, 15(13), pp. 1901-1904. Wiley-VCH 10.1002/cbic.201402116

[img] Text
1901_ftp.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (924kB) | Request a copy

Tricyclo-DNA (tc-DNA) is a conformationally restricted oligonucleotide analogue that exhibits promising properties as a robust antisense agent. Here we report on the synthesis and biochemical characterization of tc-TTP, the triphosphate of a tc-DNA nucleoside containing the base thymine. Tc-TTP turned out to be a substrate for the Vent (exo−) DNA polymerase, a polymerase that allows for multiple incorporations of tc-T nucleotides under primer extension reaction conditions. However, the substrate acceptance is rather low, as also observed for other sugar-modified analogues. Tc-TTP and tc-nucleotide-containing templates do not sustain enzymatic polymerization under physiological conditions; this indicates that tc-DNA-based antisense agents will not enter natural metabolic pathways that lead to long-term toxicity.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Hollenstein, Marcel and Leumann, Christian

Subjects:

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

ISSN:

1439-4227

Publisher:

Wiley-VCH

Language:

English

Submitter:

Christian Leumann

Date Deposited:

02 Oct 2014 13:39

Last Modified:

08 Dec 2014 15:21

Publisher DOI:

10.1002/cbic.201402116

Uncontrolled Keywords:

nucleoside triphosphates oligonucleotides polymerases primer extension tricyclo-DNA

BORIS DOI:

10.7892/boris.58826

URI:

https://boris.unibe.ch/id/eprint/58826

Actions (login required)

Edit item Edit item
Provide Feedback