DNA base flipping by a base pair-mimic nucleoside

On the basis of non-covalent bond interactions in nucleic acids, we synthesized the deoxyadenosine derivatives tethering a phenyl group (X) and a naphthyl group (Z) by an amide linker, which mimic a Watson–Crick base pair. Circular dichroism spectra indicated that the duplexes containing X and Z formed a similar conformation regardless of the opposite nucleotide species (A, G, C, T and an abasic site analogue F), which was not observed for the natural duplexes. The [Formula: see text] values among the natural duplexes containing the A/A, A/G, A/C, A/T and A/F pairs differed by 5.2 kcal mol(−1) while that among the duplexes containing X or Z in place of the adenine differed by only 1.9 or 2.8 kcal mol(−1), respectively. Fluorescence quenching experiments confirmed that 2-amino purine opposite X adopted an unstacked conformation. The structural and thermodynamic analyses suggest that the aromatic hydrocarbon group of X and Z intercalates into a double helix, resulting in the opposite nucleotide base flipping into an unstacked position regardless of the nucleotide species. This observation implies that modifications at the aromatic hydrocarbon group and the amide linker may expand the application of the base pair-mimic nucleosides for molecular biology and biotechnology

The duplexes containing the 2-amino purine nucleotide (P) opposite W (A, T, X or •), forming the A/P, T/P or X/P pair or a single P-bulge, respectively

<p><b>Copyright information:</b></p><p>Taken from "DNA base flipping by a base pair-mimic nucleoside"</p><p>Nucleic Acids Research 2005;33(22):7111-7119.</p><p>Published online 15 Dec 2005</p><p>PMCID:PMC1316115.</p><p>© The Author 2005. Published by Oxford University Press. All rights reserved</p> The 2-amino purine nucleotide is adjacent to () two cytosines or () two guanines