title: Effective Inhibition of Cellular ROS Production by MXCXXC-Type Peptides: Potential Therapeutic Applications in Copper-Homeostasis Disorders.
abstract: Cyclic and acyclic peptides with sequences derived from metallochaperone binding sites, but differing at position 2, were analyzed for their inhibitory reactivity towards cellular ROS (reactive oxygen species) formation and catalytic activity towards oxidation with H2 O2 , in comparison with three commercial drugs clinically employed in chelation therapy for Wilson's disease. Acyclic peptides were more effective inhibitors than the cyclic ones, with one leading peptide with threonine at position 2 systematically showing the highest efficiency in reducing cellular ROS levels and in inhibiting Cu oxidation. This peptide was more effective than all commercial drugs in all aspects analyzed, and showed no toxicity towards human colon HT-29 cancer cells at concentrations 10-100 times higher than the IC50 of the commercial drugs, corroborating its high medicinal potential.
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, 9190401, Jerusalem, Israel.
authors.forename: Michal S
authors.initials: MS
authors.lastname: Shoshan
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, 9190401, Jerusalem, Israel. edit.tshuva@mail.huji.ac.il.
authors.forename: Edit Y
authors.initials: EY
authors.lastname: Tshuva
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D000079922:Copper Transport Proteins; D019073:HT29 Cells; D006527:Hepatolenticular Degeneration / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D020128:Inhibitory Concentration 50; D056511:Metallochaperones / Q000737:chemistry / Q000378:metabolism; D018832:Molecular Chaperones; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000737:chemistry* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
chemical_list: C474500:ATOX1 protein, human; D056831:Coordination Complexes; D000079922:Copper Transport Proteins; D056511:Metallochaperones; D018832:Molecular Chaperones; D010455:Peptides; D017382:Reactive Oxygen Species; D003300:Copper; D006861:Hydrogen Peroxide
keywords: ROS; Wilson's disease⋅; copper; metallochaperones; peptides