Nucleic Acids Research Advance Access originally published online on May 3, 2007
Nucleic Acids Research 2007 35(10):3367-3374; doi:10.1093/nar/gkm210
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Nucleic Acids Research, 2007, Vol. 35, No. 10 3367-3374
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Chemistry |
On the stability of peptide nucleic acid duplexes in the presence of organic solvents
Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, The Panum Institute, Blegdamsvej 3c, DK-2200 Copenhagen N, Denmark
*To whom correspondence should be addressed. Tel: +45 35 327762; Fax: +45 35 396042; Email: pen{at}imbg.ku.dk
Received January 11, 2007. Accepted March 27, 2007.
Nucleic acid double helices are stabilized by hydrogen bonding and stacking forces (a combination of hydrophobic, dispersive and electrostatic forces) of the base pairs in the helix. One would predict the hydrogen bonding contributions to increase and the stacking contributions to decrease as the water activity in the medium decreases. Study of nucleobase paired duplexes in the absence of water and ultimately in pure aprotic, non-polar organic solvents is not possible with natural phosphodiester nucleic acids due to the ionic phosphate groups and the associated cations, but could be possible with non-ionic nucleic acid analogues or mimics such as peptide nucleic acids. We now report that peptide nucleic acid (PNA) (in contrast to DNA) duplexes show almost unaffected stability in up to 70% dimethylformamide (DMF) or dioxane, and extrapolation of the data to conditions of 100% organic solvents indicates only minor (or no) destabilization of the PNA duplexes. Our data indicate that stacking forces contribute little if at all to the duplex stability under these conditions. The differences in behaviour between the PNA and the DNA duplexes are attributed to the differences in hydration and counter ion release rather than to the differences in nucleobase interaction. These results support the possibility of having stable nucleobase paired double helices in organic solvents.