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Oligonucleotides DNA containing 8-trifluoromethyl-2′-deoxyguanosine for observing Z-DNA structure

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 p...

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Detalles Bibliográficos
Autores principales: Bao, Hong-Liang, Masuzawa, Tatsuki, Oyoshi, Takanori, Xu, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367190/
https://www.ncbi.nlm.nih.gov/pubmed/32678885
http://dx.doi.org/10.1093/nar/gkaa505
Descripción
Sumario: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 ((F)G). 2D NMR strongly suggested that (F)G 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(19)F NMR spectroscopy for the first time. These results provide valuable information to allow understanding of the structure and function of Z-DNA.