Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties

Autor: Antonio Magrì, Irina Naletova, Alessandro Giuffrida, Giovanni Tabbì, Cristina Satriano, Giuseppe Pappalardo, Francesco Attanasio, V. G. Nicoletti
Rok vydání: 2016
Předmět:
Zdroj: Journal of inorganic biochemistry 164 (2016): 59–69. doi:10.1016/j.jinorgbio.2016.08.013
info:cnr-pdr/source/autori:Magri, Antonio; Tabbi, Giovanni; Giuffrida, Alessandro; Pappalardo, Giuseppe; Satriano, Cristina; Naletova, Irina; Nicoletti, Vincenzo G.; Attanasio, Francesco/titolo:Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties/doi:10.1016%2Fj.jinorgbio.2016.08.013/rivista:Journal of inorganic biochemistry/anno:2016/pagina_da:59/pagina_a:69/intervallo_pagine:59–69/volume:164
ISSN: 1873-3344
DOI: 10.1016/j.jinorgbio.2016.08.013
Popis: Semax is a heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) that encompasses the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone and a C-terminal Pro-Gly-Pro tripeptide. N-terminal amino group acetylation (Ac-Semax) modulates the chemical and biological properties of parental peptide, modifying the ability of Semax to form complex species with Cu(II) ion. At physiological pH, the main complex species formed by Ac-Semax, [CuLH − 2 ] 2 − , consists in a distorted CuN 3 O chromophore with a weak apical interaction of the methionine sulphur. Such a complex differs from the Cu(II)-Semax complex system, which exhibits a CuN 4 chromophore. The reduced ligand field affects the [CuLH − 2 ] 2 − formal redox potential, which is more positive than that of Cu(II)-Semax corresponding species. In the amino-free form, the resulting complex species is redox-stable and unreactive against ascorbic acid, unlike the acetylated form. Semax acetylation did not protect from Cu(II) induced toxicity on a SH-SY5Y neuroblastoma cell line, thus demonstrating the crucial role played by the free NH 2 terminus in the cell protection. Since several brain diseases are associated either to Cu(II) or Zn(II) dyshomeostasis, here we characterized also the complex species formed by Zn(II) with Semax and Ac-Semax. Both peptides were able to form Zn(II) complex species with comparable strength. Confocal microscopy imaging confirmed that peptide group acetylation does not affect the Zn(II) influx in neuroblastoma cells. Moreover, a punctuate distribution of Zn(II) within the cells suggests a preferred subcellular localization that might explain the zinc toxic effect. A future perspective can be the use of Ac-Semax as ionophore in antibody drug conjugates to produce a dysmetallostasis in tumor cells.
Databáze: OpenAIRE
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