VIPER, a new TLR4 Signaling Peptide Inhibitor for Cell Signaling
VIPER, short for viral inhibitory peptide of TLR4 is derived from vaccinia virus, protein A46.
It is a TLR4 signaling specific inhibitor and interacts with Mal
adaptor molecules in the TLR4 signaling complex¹. For example, VIPER inhibits activation of the NF-kB signaling pathway by LPS in the IMGENEX stable reporter cell line TLR4/MD-2/NF-kB SEAPorter™ 293 HEK cells
VIPER (+ control peptide)
1 mg each
TLR ligand recognition of pathogens or self antigens and their binding leads to cell signaling responses which most often include NF-κB
and/or interferon regulatory factors (IRF
) by triggering via TIR domain adaptor molecules. Cell signaling through TLR4
signaling is mediated through MyD88
, MyD88 adaptor-like (Mal) and TRIF-related adaptor molecules (TRAM
). The strategy of developing decoy peptide inhibitors such as VIPER, which inhibits TLR4 but not other TLR pathways, is one example of how specific aspects of a given TLR signaling pathway can be explored. The concept is to retain functionality of other TLR signaling pathways while inhibiting and determining relative contribution of TLR4 signaling to eventual positive anti-pathogen responses or alternatively negative autoimmune responses.
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