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Both metal-chelating and free radical-scavenging synthetic pentapeptides as efficient inhibitors of reactive oxygen species generation †

Abstract : Reactive oxygen species (ROS) are major sources of oxidative stress playing prominent roles in the development of several pathologies including cardiovascular and neurodegenerative diseases or cancers. The presence of transition biometal ions, specifically copper and iron, induces ROS formation by catalyzing the reduction of molecular oxygen to superoxide anion (O 2 À), hydrogen peroxide (H 2 O 2) and hydroxyl (HO) radical. To limit ROS production and their detrimental effects, we report on the synthesis, physicochemical studies and antioxidant assays of an innovative series of synthetic pentapeptides exhibiting a dual direct/indirect mode of action, both as iron(III)-chelators and as radical scavengers. These combined effects lead to a drastic reduction of in vitro reactive oxygen species production up to 95% for the more reactive hydroxyl radical. Significance to metallomics We report herein on a new series of peptides exhibiting iron(III)-chelation abilities from acidic to neutral pH corresponding to conditions in which redox-active iron(III) is found in vivo, such as in both the gastrointestinal tract and the lysosomal iron labile pool, and in the blood plasma, respectively. Thanks to their chelating properties and their inherent design, this series of peptides act as effective antioxidants based on a dual indirect (i.e., inhibition of the metal redox activity) and direct (i.e., hydroxyl radical scavenging) mode of action, drastically limiting the production of reactive oxygen species up to À99% for the hydroxyl radical.
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https://hal.univ-lorraine.fr/hal-02903146
Contributor : Loic Stefan <>
Submitted on : Wednesday, July 22, 2020 - 3:11:16 PM
Last modification on : Tuesday, September 14, 2021 - 5:42:01 PM
Long-term archiving on: : Tuesday, December 1, 2020 - 1:54:53 AM

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Gizella Csire, Laetitia Canabady-Rochelle, Marie-Christine Averlant-Petit, Katalin Selmeczi, Loïc Stefan. Both metal-chelating and free radical-scavenging synthetic pentapeptides as efficient inhibitors of reactive oxygen species generation †. Metallomics, Royal Society of Chemistry, 2020, ⟨10.1039/d0mt00103a⟩. ⟨hal-02903146⟩

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