Use of cell permeable NBD peptides for suppression of inflammation.

Nuclear factor (NF)-kappaB 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-kappaB activation pathway has become a major target for development of novel therapies for inflammatory diseases and cancer. However, the indispensable role played by NF-kappaB 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-kappaB activity, while sparing the protective functions of basal NF-kappaB activity, would be of greater therapeutic value and would likely display fewer undesired side effects. The recent identification and characterisation of the NF-kappaB essential modulator (NEMO)-binding domain (NBD) peptide that can block the activation of the IkappaB kinase (IKK) complex, have provided an opportunity to selectively abrogate the inflammation induced activation of NF-kappaB 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.