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 (O2˙-), hydrogen peroxide (H2O2) 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.
Highlights
Metal ions are naturally occurring in living organisms and play pivotal roles in a wide variety of physiological processes including photosynthesis, respiration, metabolism, transmission of nervous influx or protection against pathogenic agents.[1]
Among the transition metal ions having in vivo roles, copper and iron are associated with several biological processes and the misregulation of their concentration, homeostasis or metabolism are at the origin of pathologies (e.g., Wilson’s and Menkes diseases, anaemia, cancers).[2,3]
The indirect mode of action is based on metal chelation, an approach that has demonstrated its effectiveness on reduction of reactive oxygen species (ROS) production and on ROS-mediated pathologies.[10,20,21,22]
Summary
Metal ions are naturally occurring in living organisms and play pivotal roles in a wide variety of physiological processes including photosynthesis, respiration, metabolism, transmission of nervous influx or protection against pathogenic agents.[1]. Paper inherent advantages in terms of diversity, modularity, selectivity, efficiency, safety and tolerability.[12,13] several antioxidant peptides have been reported, mainly identified a posteriori via LC/MS/MS analyses from hydrolysates of natural resources[14,15] (e.g., milk, vegetables, cereals,[16,17] algae, animals18) exhibiting antioxidant activities. This usual approach remains challenging and suffers from several drawbacks:[14,19] timeconsuming, expensive, hazardous and uncertain in terms of quantity and recovery, drastically limiting the discovery of effective antioxidant peptides. We assume that a more rational strategy is required; we report on the design, synthesis, physicochemical studies and antioxidant assays of a new series of pentapeptides exhibiting drastic inhibition of ROS production thanks to a dual direct/indirect mode of action, i.e., both Fe(III)-chelating and radical scavenging properties
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