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Book of Abstracts: Albany 2005

category image Volume 22
No. 6
June 2005

NMR Solution Structure of a DNA Interstrand Cross-link Obtained via a Novel Furan Oxidation Strategy

With the advent of antisense and antigene approach, various cross-linking molecules have been synthesized and successfully applied in medicine. An analogous strategy involves the synthesis of short modified oligonucleotides (ONs) that have the possibility to form a crosslink with a complementary strand. This approach is hampered by the fact that the ON must enter into the cell, and at the same time be inert towards other cellular targets. These modified ONs are also used in model studies of DNA-repair enzymes (1). The repair enzymes render the cell resistant against chemotherapeutics.

Furan is toxic due to the in vivo oxidation catalyzed by cytochrome P-450. Inspired by this toxicity our group in Gent has developed a 2?/2?-furan-modified nucleoside, where the furan is used as a masked functionality. This furan can be oxidized in situ to the corresponding enal to trigger cross-linking with a complementary ON (2).

With the help of NMR-spectroscopy and molecular modelling, we are currently studying the position of the cross-link and the nature of the chemical bond that is formed.

Acknowledgement

This research has been supported by the Sixth Framework Programme Marie Curie Host Fellowships for Early Stage Research Training under contract number MEST-CT-2004-504018

References and Footnotes
  1. Noll, D., Noronha, A., Wilds, C., and Miller, P. Frontiers in Bioscience 9, 421-437 (2004).
  2. Halilia, S., Velasco, T., De Clercq, P., Madder, A. Chem. Comm. 7, 936-938 (2005).

Kristof Stevens1,2,*
Annemieke Madder1
Michael Petersen2

1Laboratory for Organic and Biomimetic Chemistry
University of Gent
Krijgslaan 281 S4, 9000 Gent
Belgium
2Departement of Chemistry
University of Southern Denmark
Campusvej 55, 5230 Odense M
Denmark

*Phone: +3292644472
Fax: +3292644472
Email: kst@chem.sdu.dk