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An intracellular targeted NLS peptide inhibitor of karyopherin alpha:NF-kappa B interactions
Mark D Cunningham1, Jeffrey Cleaveland, Steven G Nadler
1Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA.
Abstract:
The nuclear import of transcription factors involves proteins termed karyopherins. Previously, we described an intracellular targeted dual nuclear localization sequence (NLS) peptide inhibitor of processes dependent upon the transcription factor NF-kappa B. We have now developed a homogeneous solution based assay and show that NF-kappa B interacts with karyopherin alpha and that the dual NLS peptide inhibits this interaction. We also show that both L- and D-amino acid containing peptides bind well to karyopherin alpha 2, whereas, the L-amino acid peptides bind more efficiently than the D-amino acid peptide to karyopherin alpha1.