4.7 Article

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

Journal

DALTON TRANSACTIONS
Volume 49, Issue 7, Pages 2323-2330

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/c9dt04619d

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Funding

  1. Ecole Normale Superieure Paris Saclay
  2. ANR [ANR-10-IDEX-0001-02 PSL*, ANR-15-CE07-0027]
  3. Fondation pour la Recherche Biomedicale [DIE20151234413]

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A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or F-x-r-F-x-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 mu M. 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.

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