TY - JOUR
T1 - Anti-inflammatory activity of superoxide dismutase mimics functionalized with cell-penetrating peptides
AU - Mathieu, Emilie
AU - Bernard, Anne Sophie
AU - Ching, H. Y.Vincent
AU - Somogyi, Andrea
AU - Medjoubi, Kadda
AU - Fores, Jennifer Rodon
AU - Bertrand, Hélène C.
AU - Vincent, Amandine
AU - Trépout, Sylvain
AU - Guerquin-Kern, Jean Luc
AU - Scheitler, Andreas
AU - Ivanović-Burmazović, Ivana
AU - Seksik, Philippe
AU - Delsuc, Nicolas
AU - Policar, Clotilde
N1 - Funding Information:
We thank Ecole Normale Supérieure Paris Saclay for E. Mathieu PhD fellowship, TGE RENARD (FR 3443, CNRS) and UMR8601 for access to the EPR spectrometer for the EPR experiments, Dr F. Poyer, and Pr. S. Marco for useful discussions and help in cryofixed samples preparation, Dr F. Lambert for help in synthesis, B. Goetz for help with ICP-MS, Pr. A. Leturque and M. Moreau for access to the WES, Dr G. Sommeria-Klein for useful discussions. We also thank Dr L. Grimaud for help for electrochemistry experiments, Dr S. Sagan for ITC and the IBPS SU, FR3631 mass spectrometry core facilities for access to the MALDI-TOF spectrometer, M. Zoumpoulaki for recording MS-MS spectra and J. Vinh for access to the mass spectrophotometer in SMBP-ESPCI. Association François Aupetit, ANR (ANR-10-IDEX-0001-02 PSL* project INOCELLCHEM and ANR-15-CE07-0027 project MAGIC), Fondation pour la Recherche Biomédicale (project DIE20151234413) are acknowledged for financial supports. SOLEIL committee is acknowledged for beamtime.
Funding Information:
Philippe Seksik declares consulting fees from Takeda, Abbvie, Merck-MSD and Biocodex, grants from Biocodex, sponsored travel from Merck-MSD and Takeda. These COI are not related with the present work.
Publisher Copyright:
This journal is © The Royal Society of Chemistry.
PY - 2020/2/21
Y1 - 2020/2/21
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85079666503
U2 - 10.1039/c9dt04619d
DO - 10.1039/c9dt04619d
M3 - Article
C2 - 32022053
AN - SCOPUS:85079666503
SN - 1477-9226
VL - 49
SP - 2323
EP - 2330
JO - Dalton Transactions
JF - Dalton Transactions
IS - 7
ER -