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Ann Rheum Dis 65:iii75-iii82 doi:10.1136/ard.2006.058438
  • Novel targets III

Use of cell permeable NBD peptides for suppression of inflammation

  1. I Strickland,
  2. S Ghosh
  1. Section of Immunobiology, Department of Biophysics and Biochemistry, Yale University, New Haven, CT, USA
  1. Correspondence to:
    Sankar Ghosh
    sankar.ghosh{at}yale.edu

    Abstract

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

    Footnotes

    • Competing interests: none declared