title: Trifluoroacetylated tyrosine-rich D-tetrapeptides have potent antioxidant activity.
abstract: 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 ORACFLassay, 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 CF3group 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.
authors.affiliation: Istitute of Biostructures and Bioimaging, CNR, via Mezzocannone 16, 80134 Naples, Italy; Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), via Mezzocannone 16, 80134 Naples, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Sandomenico
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Università della Campania Luigi Vanvitelli, via Vivaldi, 43, 80100 Caserta, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Severino
authors.affiliation: Arterra Biosciences srl, via B. Brin 69, 80142 Naples, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Apone
authors.affiliation: Arterra Biosciences srl, via B. Brin 69, 80142 Naples, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: De Lucia
authors.affiliation: Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), via Mezzocannone 16, 80134 Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Caporale
authors.affiliation: Istitute of Biostructures and Bioimaging, CNR, via Mezzocannone 16, 80134 Naples, Italy; Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), via Mezzocannone 16, 80134 Naples, Italy.
authors.forename: Nunzianna
authors.initials: N
authors.lastname: Doti
authors.affiliation: Department of Pharmacy, University of Naples Federico II, via Mezzocannone, 16, 80134 Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Russo
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Università della Campania Luigi Vanvitelli, via Vivaldi, 43, 80100 Caserta, Italy.
authors.forename: Rosita
authors.initials: R
authors.lastname: Russo
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Università della Campania Luigi Vanvitelli, via Vivaldi, 43, 80100 Caserta, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Rega
authors.affiliation: Department of Biological Chemistry and Biotechnology, University of Perugia, via Elce di Sotto 8, 06123 Perugia, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Del Giacco
authors.affiliation: Istitute of Biostructures and Bioimaging, CNR, via Mezzocannone 16, 80134 Naples, Italy; Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), via Mezzocannone 16, 80134 Naples, Italy; Department of Pharmacy, University of Naples Federico II, via Mezzocannone, 16, 80134 Naples, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Falcigno
authors.affiliation: Istitute of Biostructures and Bioimaging, CNR, via Mezzocannone 16, 80134 Naples, Italy; Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), via Mezzocannone 16, 80134 Naples, Italy. Electronic address: mruvo@yahoo.com.
authors.forename: Menotti
authors.initials: M
authors.lastname: Ruvo
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Università della Campania Luigi Vanvitelli, via Vivaldi, 43, 80100 Caserta, Italy. Electronic address: angela.chambery@unina2.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Chambery
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D019151:Peptide Library; D010455:Peptides; D017382:Reactive Oxygen Species
keywords: Antioxidants; Lipid peroxidation; ORAC assay; Peptide libraries