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Base pairing involving artificial bases in vitro and in vivo .
- Source :
-
Chemical science [Chem Sci] 2016 Feb 01; Vol. 7 (2), pp. 995-1010. Date of Electronic Publication: 2015 Nov 10. - Publication Year :
- 2016
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Abstract
- Herein we report the synthesis of N <superscript>8</superscript> -glycosylated 8-aza-deoxyguanosine ( N <superscript>8</superscript> -8-aza-dG) and 8-aza-9-deaza-deoxyguanosine ( N <superscript>8</superscript> -8-aza-9-deaza-dG) nucleotides and their base pairing properties with 5-methyl-isocytosine (d-isoC <superscript>Me</superscript> ), 8-amino-deoxyinosine (8-NH <subscript>2</subscript> -dI), 1- N -methyl-8-amino-deoxyinosine (1-Me-8-NH <subscript>2</subscript> -dI), 7,8-dihydro-8-oxo-deoxyinosine (8-Oxo-dI), 7,8-dihydro-8-oxo-deoxyadenosine (8-Oxo-dA), and 7,8-dihydro-8-oxo-deoxyguanosine (8-Oxo-dG), in comparison with the d-isoC <superscript>Me</superscript> :d-isoG artificial genetic system. As demonstrated by T <subscript>m</subscript> measurements, the N <superscript>8</superscript> -8-aza-dG:d-isoC <superscript>Me</superscript> base pair formed less stable duplexes as the C:G and d-isoC <superscript>Me</superscript> :d-isoG pairs. Incorporation of 8-NH <subscript>2</subscript> -dI versus the N <superscript>8</superscript> -8-aza-dG nucleoside resulted in a greater reduction in T <subscript>m</subscript> stability, compared to d-isoC <superscript>Me</superscript> :d-isoG. Insertion of the methyl group at the N <superscript>1</superscript> position of 8-NH <subscript>2</subscript> -dI did not affect duplex stability with N <superscript>8</superscript> -8-aza-dG, thus suggesting that the base paring takes place through Hoogsteen base pairing. The cellular interpretation of the nucleosides was studied, whereby a lack of recognition or mispairing of the incorporated nucleotides with the canonical DNA bases indicated the extent of orthogonality in vivo . The most biologically orthogonal nucleosides identified included the 8-amino-deoxyinosines (1-Me-8-NH <subscript>2</subscript> -dI and 8-NH <subscript>2</subscript> -dI) and N <superscript>8</superscript> -8-aza-9-deaza-dG. The 8-oxo modifications mimic oxidative damage ahead of cancer development, and the impact of the MutM mediated recognition of these 8-oxo-deoxynucleosides was studied, finding no significant impact in their in vivo assay.
Details
- Language :
- English
- ISSN :
- 2041-6520
- Volume :
- 7
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Chemical science
- Publication Type :
- Academic Journal
- Accession number :
- 29896368
- Full Text :
- https://doi.org/10.1039/c5sc03474d