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Nucleic Acids Research 2005 33(4):1182-1192; doi:10.1093/nar/gki257
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Published online 24 February 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

Article

The effect of chemical modifications on the thermal stability of different G-quadruplex-forming oligonucleotides

Barbara Saccà, Laurent Lacroix and Jean-Louis Mergny*

Laboratoire de Biophysique, Muséum National d'Histoire Naturelle USM503 INSERM U565, CNRS UMR 5153, 43 rue Cuvier, 75231 Paris cedex 05, France

*To whom correspondence should be addressed. Tel: +33 1 40 79 36 89; Fax: +33 1 40 79 37 05; Email: mergny{at}vnumail.com

Received December 6, 2005. Revised January 21, 2005. Accepted January 31, 2005.

A systematic study of the thermal and conformational properties of chemically modified G-quadruplexes of different molecularities is reported. The effect of backbone charge and atom size, thymine/uracyl substitution as well as the effect of modification at the ribose 2'-position was analyzed by UV spectroscopy. Additional calorimetric studies were performed on different modified forms of the human telomeric sequence. Determination of the differential spectra allowed more insights into the conformational properties of the oligonucleotides. Lack of negative charge at the phosphate backbone yielded to a general destabilization of the G-quadruplex structure. On the other hand, substitution of thymine with uracyl resulted in a moderate or strong stabilization of the structure. Additional modification at the sugar 2'-position gave rise to different effects depending on the molecularity of the quadruplex. In particular, loss of hydrogen bond capacity at the 2'-position strongly affected the conformation of the G-quadruplex. Altogether, these results demonstrate that the effect of some modifications depends on the sequence context, thus providing helpful information for the use of chemically modified quadruplexes as therapeutic agents or as structural elements of supramolecular complexes.

Present address: Barbara Saccà, Laboratoire de Stabilité des Génomes, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France


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