Cell penetrating peptide inhibitors of nuclear factor-kappa B.
The nuclear factor kappa B (NF-kappaB) transcription factors are activated by a range of stimuli including pro-inflammatory cytokines. Active NF-kappaB regulates the expression of genes involved in inflammation and cell survival and aberrant NF-kappaB activity plays pathological roles in certain types of cancer and diseases characterized by chronic inflammation. NF-kappaB signaling is an attractive target for the development of novel anti-inflammatory or anti-cancer drugs and we discuss here how the method of peptide transduction has been used to specifically target NF-kappaB. Peptide transduction relies on the ability of certain small cell-penetrating peptides (CPPs) to enter cells, and a panel of CPP-linked inhibitors (CPP-Is) has been developed to directly inhibit NF-kappaB signaling. Remarkably, several of these NF-kappaB-targeting CPP-Is are effective in vivo and therefore offer exciting potential in the clinical setting.
Orange
J S
JS
Department of Pediatrics, University of Pennsylvania School of Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
May
M J
MJ
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D051550:I-kappa B Kinase / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D002352:Carrier Proteins; D016328:NF-kappa B; D010455:Peptides; D051550:I-kappa B Kinase