Trifluoroacetylated tyrosine-rich D-tetrapeptides have potent antioxidant activity

Publication date: Available online 24 January 2017
Source:Peptides
Author(s): Annamaria Sandomenico, Valeria Severino, Fabio Apone, Adriana De Lucia, Andrea Caporale, Nunzianna Doti, Anna Russo, Rosita Russo, Camilla Rega, Tiziana del Giacco, Lucia Falcigno, Menotti Ruvo, Angela Chambery
The term "oxidative stress" indicates a set of chemical reactions unleashed by a disparate number of events inducing DNA damage, lipid peroxidation, protein modification and other effects, which are responsible 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 or proliferation in dependence of cell status and of targeted molecules. In this context, new antioxidants preventing 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 ORACFL assay, we have isolated potent anti-oxidant compounds with well-defined structures. Most effective peptides are N-terminally trifluoroacetylated (CF3) and have the sequence tyr-tyr-his-pro or tyr-tyr-pro-his. Slight changes in the sequence or removal of the CF3 group strongly reduced antioxidant ability, suggesting an active role of both the fluorine atoms and of peptide structure. We have determined the NMR solution structures of the active peptides and found a common structural motif that could underpin the radical scavenging activity. The peptides protect keratinocytes from exogenous oxidation, thereby from potential external damaging cues, suggesting their use as skin ageing protectant and as cell surviving agents.

Graphical abstract

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