Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion and protective ability against metal induced cell toxicity

•Heptapeptide Semax is an analog of the adrenocorticotrophic hormone (ACTH) (4-10) fragment.•Semax peptide is able to complex copper(II) in an albumin-like mode.•A reduced copper induced cytotoxicity was observed in the presence of Semax.

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 pH 5 the [CuLH− 2]2 − species becomes predominant with the donor atoms around copper arranged in a 4 N 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.

Graphical abstractThe heptapeptide Semax is an analog of the adrenocorticotropic hormone (ACTH) 4-10 fragment. This study shows the metal binding ability and protective activity of Semax against copper induced cytotoxicity.Figure optionsDownload full-size imageDownload as PowerPoint slide