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

摘要

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 center dot(-)), hydrogen peroxide (H2O2) and hydroxyl (HO center dot) 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 ofin vitroreactive oxygen species production up to 95% for the more reactive hydroxyl radical.