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

Emilie Mathieu (1, 2, 3, 4) , Anne-Sophie Bernard (1, 2, 3, 4) , H. Y. Vincent Ching (1, 2, 3, 4) , Andrea Somogyi (5) , Kadda Medjoubi (5) , Jennifer Rodon Fores (1, 2, 3, 4) , Hélène C Bertrand (1, 2, 3, 4) , Amandine Vincent (1, 2, 3, 4) , Sylvain Trépout (6, 7) , Jean-Luc Guerquin-Kern (7, 6) , Andreas Scheitler (8, 9) , Ivana Ivanović-Burmazović (9, 8) , Philippe Seksik (1, 3) , Nicolas Delsuc (1, 2, 3, 4) , Clotilde Policar (1, 2, 3, 4)

1 LBM UMR 7203 - Laboratoire des biomolécules
2 PSL - Université Paris sciences et lettres
3 SU - Sorbonne Université
4 ENS-PSL - École normale supérieure - Paris
5 SSOLEIL - Synchrotron SOLEIL
6 Institut Curie [Paris]
7 CMBC - Chimie et modélisation pour la biologie du cancer
8 FAU - Friedrich-Alexander Universität Erlangen-Nürnberg = University of Erlangen-Nuremberg
9 Department of Chemistry and Pharmacy

A superoxide dismutases 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 Mn 2+ , 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.

Mots clés: anti-inflammatory compounds; multimodal imaging; oxidative stress; cell penetrating peptides; X-fluorescence imaging; Superoxide dismutase mimics

Domaines: Chimie inorganique; Chimie de coordination; Chimie organique; Autre

Emilie Mathieu, Anne-Sophie Bernard, H. Y. Vincent Ching, Andrea Somogyi, Kadda Medjoubi, et al.. Anti-inflammatory activity of superoxide dismutase mimics functionalized with cell- penetrating peptides. Dalton Transactions, 2020, 49 (7), pp.2323-2330. ⟨10.1039/C9DT04619D⟩. ⟨hal-02521252⟩