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

• Published in: Dalton transactions : an international journal of inorganic chemistry Vol. 49; no. 7; pp. 2323 - 233
• Main Authors: Mathieu, Emilie, Bernard, Anne-Sophie, Ching, H. Y. Vincent, Somogyi, Andrea, Medjoubi, Kadda, Fores, Jennifer Rodon, Bertrand, Hélène C, Vincent, Amandine, Trépout, Sylvain, Guerquin-Kern, Jean-Luc, Scheitler, Andreas, Ivanovi -Burmazovi, Ivana, Seksik, Philippe, Delsuc, Nicolas, Policar, Clotilde
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 21.02.2020
• Subjects: Assaying; Chemical properties; Chemical Sciences; Coordination chemistry; Electrochemical analysis; Electrochemistry; Inorganic chemistry; Organic chemistry; Other; Oxidation; Peptides; Statistical analysis; Superoxide dismutase; Titration calorimetry; Toxicity; X-fluorescence imaging; cell penetrating peptides; anti-inflammatory compounds; Superoxide dismutase mimics; multimodal imaging; oxidative stress
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c9dt04619d

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 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. A superoxide dismutase mimic was functionalized with three peptides: -R9, -RRWWRRWRR or -F x -r-F x -K (MPP). They were studied in intestinal epithelial cells in an inorganic cellular chemistry approach: quantification, distribution and bio-activity.