Sequence-specific interaction of alpha-beta-anomeric double-stranded DNA with the p50 subunit of NF kappa B: application to the decoy approach.
The potential use of alpha-beta-anomeric duplex oligonucleotides to inhibit transcription factor activity by the decoy approach is investigated in this report. Indeed, several alpha-beta-anomeric heteroduplexes display a sequence-specific interaction with the p50 subunit of the transcription factor NF kappa B. 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 NF kappa B. However, all the alpha-beta-anomeric heteroduplexes do not interact with the p50 subunit; the sequence of the chirally natural beta-anomeric strand may explain the different recognition properties of the protein. The analysis of the appropriate beta-anomeric sequences is consistent with a preferential interaction of the p50 subunit with one strand of double-stranded DNA.
Tanaka
H
H
Laboratoire de Biochimie-Enzymologie, INSERM U140, CNRS URA147, Institut Gustave Roussy, Villejuif, France.
Vickart
P
P
Bertrand
J R
JR
Rayner
B
B
Morvan
F
F
Imbach
J L
JL
Paulin
D
D
Malvy
C
C
D001483:Base Sequence; D001667:Binding, Competitive; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004355:Drug Stability; D015870:Gene Expression / Q000187:drug effects; D005982:Glutathione Transferase / Q000235:genetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013816:Thermodynamics; D014162:Transfection; D014746:Vimentin / Q000235:genetics
D046911:Macromolecular Substances; D016328:NF-kappa B; D009692:Nucleic Acid Heteroduplexes; D011993:Recombinant Fusion Proteins; D014746:Vimentin; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase; D005982:Glutathione Transferase