Journal
NUCLEIC ACIDS RESEARCH
Volume 48, Issue 13, Pages 7041-7051Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa505
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Funding
- Japan Society for the Promotion of Science KAKENHI [17H03091, 20K15402]
- Naito Foundation
- Ichiro Kanehara Foundation
- Grants-in-Aid for Scientific Research [17H03091, 20K15402] Funding Source: KAKEN
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Z-DNA is known to be a left-handed alternative form of DNA and has important biological roles as well as being related to cancer and other genetic diseases. It is therefore important to investigate Z-DNA structure and related biological events in living cells. However, the development of molecular probes for the observation of Z-DNA structures inside living cells has not yet been realized. Here, we have succeeded in developing site-specific trifluoromethyl oligonucleotide DNA by incorporation of 8-trifluoromethyl-2'-deoxyguanosine (FG). 2D NMR strongly suggested that FG adopted a syn conformation. Trifluoromethyl oligonucleotides dramatically stabilized Z-DNA, even under physiological salt concentrations. Furthermore, the trifluoromethyl DNA can be used to directly observe Z-form DNA structure and interaction of DNA with proteins in vitro, as well as in living human cells by F-19 NMR spectroscopy for the first time. These results provide valuable information to allow understanding of the structure and function of Z-DNA.
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