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Nucleic Acids Research, 1994, Vol. 22, No. 15 3069-3074
© 1994

MOLECULAR BIOLOGY

Sequence-specific interaction of {alpha} ß-anomeric doublestranded DNA with the p50 subunit of NFxB: application to the decoy approach

Hiroaki Tanaka*, Patrick Vickart1, Jean-Rémi Bertrand, Bernard Rayner2, François Morvan2, Jean-Louis Imbach2, Denise Paulin1 and Claude Malvy

Laboratoire de Biochimie-Enzymologie, INSERM U140, CNRS URA147, Institut Gustave Roussy, rue Camille Desmoulins 94805Villejuif Cedex 1Institut Pasteur, 25 rue du Docteur Roux 75015 Paris 2Laboratoire de Chimie Bio-Organique, CNRS UA488, Universite des Sciences et Techniques du Languedoc 34060 Montpellier cedex, France

*To whom correspondence should be addressed

Received May 3, 1994. Revised July 5, 1994. Accepted July 5, 1994.

The potential use of {alpha}-ß-anomeric duplex oligonucleotides to inhibit transcription factor activity by the decoy approach is investigated in this report. Indeed, several {alpha} ß-anomeric heteroduplexes display a sequence-specific interaction with the p50 subunit of the transcription factor NFxB. Used in a decoy approach, these duplexes interact strongly enough with this transcription factor to modulate the expression of a reporter gene, under the control of NFxB. However, all the a-jS-anomeric heteroduplexes do not interact with the p50 subunit; the sequence of the chirally natural ß-anomeric strand may explain the different recognition properties of the protein. The analysis of the appropriate ß-anomeric sequences is consistent with a preferential interaction of the p50 subunit with one strand of double-stranded DNA.


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