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

Study · Journal of inorganic biochemistry · 2015 · DOI 10.1016/j.jinorgbio.2014.09.008 · PMID 25310602

Plain-language summary

Paraphrased from the published abstract below — not a verdict on whether anything works.

In this study, the authors examined the copper(II)-binding and protective activity of the heptapeptide Semax, which encompasses sequence 4-7 of the N-terminal domain of adrenocorticotropic hormone (ACTH) plus a C-terminal Pro-Gly-Pro tripeptide. The abstract reports equilibrium studies showing three complex species, with two minor species co-existing with a predominant [CuLH-2]2- species from about pH 5, where copper adopts a 4N planar coordination in the pH range 3.6 to 5. It states reduced copper-induced cytotoxicity was observed in the presence of Semax by MTT assay on SHSY5Y neuroblastoma and RBE4 endothelial cell lines.

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.

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