A TNF-α blocking peptide that reduces NF-κB and MAPK activity for attenuating inflammation

Bioorg Med Chem. 2023 Sep 7:92:117420. doi: 10.1016/j.bmc.2023.117420. Epub 2023 Jul 20.

Abstract

Overexpression of tumor necrosis factor-α (TNF-α) is implicated in many inflammatory diseases, including septic shock, hepatitis, asthma, insulin resistance and autoimmune diseases, such as rheumatoid arthritis and Crohn's disease. The TNF-α signaling pathway is a valuable target, and anti-TNF-α drugs are successfully used to treat autoimmune and inflammatory diseases. Here, we study anti-inflammatory activity of an anti-TNF-α peptide (SN1-13, DEFHLELHLYQSW). In the cellular level assessment, SN1-13 inhibited TNF-α-induced cytotoxicity and blocks TNF-α-triggered signaling activities (IC50 = 15.40 μM). Moreover, the potential binding model between SN1-13 and TNF-α/TNFRs conducted through molecular docking revealed that SN1-13 could stunt TNF-α mediated signaling thought blocking TNF-α and its receptor TNFR1 and TNFR2. These results suggest that SN1-13 would be a potential lead peptide to treat TNF-α-mediated inflammatory diseases.

Keywords: Inflammation; Molecular docking; Peptide; TNF-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Inflammation / drug therapy
  • Molecular Docking Simulation
  • NF-kappa B* / metabolism
  • Peptides / pharmacology
  • Peptides / therapeutic use
  • Tumor Necrosis Factor Inhibitors / therapeutic use
  • Tumor Necrosis Factor-alpha* / metabolism

Substances

  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Tumor Necrosis Factor Inhibitors
  • Peptides