Anti-inflammatory activity of superoxide dismutase mimics functionalized with cell-penetrating peptides

Dalton Trans. 2020 Feb 21;49(7):2323-2330. doi: 10.1039/c9dt04619d. Epub 2020 Feb 5.

Abstract

A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or Fx-r-Fx-K (Mn1-MPP). Characterization of the physico-chemical properties of the complexes show that they share similar binding affinity for Mn2+, apparent reduction potential and intrinsic superoxide dismutase activity. However, their accumulation in cells is different (Mn1-R9 < Mn1-MPP < Mn1-RW9 < Mn1), as well as their subcellular distribution. In addition, the three functionalized-complexes display a better anti-inflammatory activity than Mn1 when assayed at 10 μM. This improvement is due to a combination of an anti-inflammatory effect of the peptidyl moiety itself, and of the SOD mimic for Mn1-RW9 and Mn1-MPP. In contrast, the enhanced anti-inflammatory activity of Mn1-R9 is solely due to the SOD mimic.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell-Penetrating Peptides / chemistry
  • Cell-Penetrating Peptides / metabolism
  • Cell-Penetrating Peptides / pharmacology*
  • HT29 Cells
  • Humans
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Molecular Structure
  • Superoxide Dismutase / chemistry
  • Superoxide Dismutase / metabolism*
  • Thermodynamics

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cell-Penetrating Peptides
  • Lipopolysaccharides
  • Superoxide Dismutase