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Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552

Abstract : Because of resistance development by cancer cells against current anticancer drugs, there is a considerable interest in developing novel antitumor agents. We have previously demonstrated that CIGB-552, a novel cell-penetrating synthetic peptide, was effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Studies of protein-peptide interactions have shown that COMMD1 protein is a major mediator of CIGB-552 antitumor activity. Furthermore, a typical serine-protease degradation pattern for CIGB-552 in BALB/c mice serum was identified, yielding peptides which differ from CIGB-552 in size and physical properties. In the present study, we show the results obtained from a comparative analysis between CIGB-552 and its main metabolites regarding physicochemical properties, cellular internalization, and their capability to elicit apoptosis in MCF-7 cells. None of the analyzed metabolites proved to be as effective as CIGB-552 in promoting apoptosis in MCF-7. Taking into account these results, it seemed important to examine their cell-penetrating capacity and interaction with COMMD1. We show that internalization, a lipid binding-dependent process, is impaired as well as metabolite-COMMD1 interaction, key component of the apoptotic mechanism. Altogether, our results suggest that features conferred by the amino acid sequence are decisive for CIGB-552 biological activity, turning it into the minimal functional unit.
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Submitted on : Monday, September 24, 2018 - 9:25:59 PM
Last modification on : Monday, October 8, 2018 - 5:44:06 PM

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Soledad Astrada, Yolanda Gomez, Exequiel Barrera, Gonzalo Obal, Otto Pritsch, et al.. Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552. Journal of Peptide Science, Wiley, 2016, 22 (11-12), pp.711 - 722. ⟨10.1002/psc.2934⟩. ⟨pasteur-01880474⟩

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