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

Emilie Mathieu, Anne-Sophie Bernard, H Y Vincent Ching, Andrea Somogyi, Kadda Medjoubi, Jennifer Rodon Fores, Hélène C Bertrand, Amandine Vincent, Sylvain Trépout, Jean-Luc Guerquin-Kern, Andreas Scheitler, Ivana Ivanović-Burmazović, Philippe Seksik, Nicolas Delsuc, Clotilde Policar (2020 Feb 6) Dalton transactions (Cambridge, England : 2003) : 49 : 2323-2330 : DOI : 10.1039/c9dt04619d

A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or F-r-F-K (Mn1-MPP). Characterization of the physico-chemical properties of the complexes show that they share similar binding affinity for Mn, 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.