title: Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion and protective ability against metal induced cell toxicity.
abstract: Heptapeptide Semax, encompassing the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone (ACTH) and a C-terminal Pro-Gly-Pro tripeptide, belongs to a short regulatory peptides family. This compound has been found to affect learning processes and to exert marked neuroprotective activities on cognitive brain functions. Dys-homeostasis of metal ions is involved in several neurodegenerative disorders and growing evidences have showed that brain is a specialized organ able to concentrate metal ions. In this work, the metal binding ability and protective activity of Semax and its metal complexes were studied. The equilibrium study clearly demonstrated the presence of three complex species. Two minor species [CuL] and [CuLH-1]- co-exist together with the [CuLH-2]2- in the pH range from 3.6 to 5. From pH5 the [CuLH-2]2- species becomes predominant with the donor atoms around copper arranged in a 4N planar coordination mode. Noteworthy, a reduced copper induced cytotoxicity was observed in the presence of Semax by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay on a SHSY5Y neuroblastoma and RBE4 endothelial cell lines.
authors.affiliation: CNR-Istituto di Biostrutture e Bioimmagini, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tabbì
authors.affiliation: CNR-Istituto di Biostrutture e Bioimmagini, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Magrì
authors.affiliation: CNR-Istituto di Biostrutture e Bioimmagini, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giuffrida
authors.affiliation: CNR-Istituto di Biostrutture e Bioimmagini, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Lanza
authors.affiliation: CNR-Istituto di Biostrutture e Bioimmagini, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pappalardo
authors.affiliation: Dipartimento di Scienze Biomediche, Università Degli Studi di Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Irina
authors.initials: I
authors.lastname: Naletova
authors.affiliation: Dipartimento di Scienze Biomediche, Università Degli Studi di Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Vincenzo Giuseppe
authors.initials: VG
authors.lastname: Nicoletti
authors.affiliation: CNR-Istituto di Biostrutture e Bioimmagini, Via P. Gaifami 18, 95126 Catania, Italy. Electronic address: francesco.attanasio@cnr.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Attanasio
authors.affiliation: CNR-Istituto di Biostrutture e Bioimmagini, Via P. Gaifami 18, 95126 Catania, Italy; Consorzio Interuniversitario C.I.R.C.S.M.B., Via C. Ulpiani 27, 70125 Bari, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Rizzarelli
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D003300:Copper / Q000737:chemistry / Q000633:toxicity*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D011199:Potentiometry / Q000379:methods
chemical_list: D010446:Peptide Fragments; D003300:Copper; C048487:ACTH (4-7), Pro-Gly-Pro-; D000324:Adrenocorticotropic Hormone
keywords: Cell viability; Copper; Semax; Speciation; Spectroscopy; Voltammetry