In search of a Hoogsteen base paired DNA duplex in aqueous solution

Journal of Biomolecular Structure & Dynamics
M H SarmaR H Sarma

Abstract

When the oligodeoxynucleotides d(A)6 and d(T)6 are mixed together in a 1:1 ratio (in 100 mM NaCl), the NH signals in the NMR spectrum gave a typical signature of Watson-Crick paired (WC) and Hoogsteen paired (H) AT base pairs. The observation indicates two schemes: Scheme I, WC and H duplexes in slow equilibrium, i.e., WC in equilibrium with H, Scheme II, the WC helix formed is unstable and that it disproportionates into a triple helix (TR) and free d(A)6. We show that (i) addition of extra d(A)6 does not change the helix composition, (ii) addition of a minor-groove specific drug Dst2 (a distamycin analogue) results in an exclusive WC helix-drug duplex, while it does not destabilize triple helix in a 1:2 mixture. In addition we have compared the melting profile, 31P NMR spectra, 1H NMR spectra and the salt dependence of the 1:1 mixture and that of a pure triple helix. All the data from the above experiments overwhelmingly favor Scheme I. However Scheme II cannot be categorically excluded. Based on 1D/2D NMR studies, we have characterized the structural properties of the Hoogsteen double helix in terms of nucleotide conformations. In addition, we computationally demonstrate that the relative stability of the WC over the H duplex...Continue Reading

References

Mar 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·D S PilchR H Shafer
Jul 25, 1989·Biochemistry·M W GermannJ H van de Sande
Dec 1, 1986·Journal of Biomolecular Structure & Dynamics·A H WangA Rich
Oct 1, 1983·Journal of Biomolecular Structure & Dynamics·S ArnottJ K Walker
Sep 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·R L Ornstein, J R Fresco
Apr 1, 1986·Journal of Computational Chemistry·Scott J WeinerDavid A Case

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Citations

Oct 1, 1994·Journal of Biomolecular Structure & Dynamics·S P JiangG Raghunathan
Mar 27, 2003·Journal of the American Chemical Society·Dev P AryaLiang Xue

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