Trifluoroacetylated tyrosine-rich D-tetrapeptides have potent antioxidant activity

tThe term “oxidative stress” indicates a set of chemical reactions unleashed by a disparate number ofevents inducing DNA damage, lipid peroxidation, protein modification and other effects, which areresponsible of altering the physiological status of cells or tissues. Excessive Reactive Oxygen Species (ROS)levels may accelerate ageing of tissues or induce damage of biomolecules thus promoting cell death orproliferation in dependence of cell status and of targeted molecules. In this context, new antioxidants pre-venting such effects may have a relevant role as modulators of cell homeostasis and as therapeutic agents.Following an approach of peptide libraries synthesis and screening by an ORACFLassay, we have isolatedpotent anti-oxidant compounds with well-defined structures. Most effective peptides are N-terminallytrifluoroacetylated (CF3) and have the sequence tyr-tyr-his-pro or tyr-tyr-pro-his. Slight changes in thesequence or removal of the CF3group strongly reduced antioxidant ability, suggesting an active role ofboth the fluorine atoms and of peptide structure. We have determined the NMR solution structures ofthe active peptides and found a common structural motif that could underpin the radical scavengingactivity. The peptides protect keratinocytes from exogenous oxidation, thereby from potential externaldamaging cues, suggesting their use as skin ageing protectant and as cell surviving agents.