Use of cell permeable NBD peptides for suppression of inflammation

Nuclear factor (NF)-kappa B is a ubiquitous and essential transcription factor whose dysregulation has been linked to numerous diseases including arthritis and cancer. It is therefore not surprising that the NF-kappa B activation pathway has become a major target for development of novel therapies for inflammatory diseases and cancer. However, the indispensable role played by NF-kappa B in many biological processes has raised concern that a complete shutdown of this pathway would have significant detrimental effects on normal cellular function. Instead, drugs that selectively target the inflammation induced NF-kappa B activity, while sparing the protective functions of basal NF-kappa B activity, would be of greater therapeutic value and would likely display fewer undesired side effects. The recent identification and characterisation of the NF-kappa B essential modulator (NEMO)binding domain (NBD) peptide that can block the activation of the I kappa B kinase (IKK) complex, have provided an opportunity to selectively abrogate the inflammation induced activation of NF-kappa B by targeting the NBD-NEMO interaction. This peptide is synthesised in tandem with a protein transduction domain sequence from Drosophila antennapedia which facilitates uptake of the inhibitory peptide into the cytosol of target cells.