Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB‐552. (November 2016)

• Record Type: Journal Article
• Authors: Astrada, Soledad; Gomez, Yolanda; Barrera, Exequiel; Obal, Gonzalo; Pritsch, Otto; Pantano, Sergio; Vallespí, Maribel G.; Bollati‐Fogolín, Mariela
• Is Part Of: Journal of peptide science. Volume 22:Number 11/12(2016:Nov.)
• Page Start: 711
• Page End: 722
• Publication Date: 2016-11
• Subjects: cell penetrating peptide -- COMMD1 -- amino acids -- apoptosis; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.2934
• Languages: English
• ISSNs: 1075-2617

Abstract

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. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Abstract : CIGB‐552 is a cell‐penetrating synthetic antitumor peptide whose exposure to mice serum yields several derived metabolites, which differ mainly in their net charge. Comparative studies between CIGB‐552 and its main derived metabolites were performed: apoptosis, cell‐penetrating capacity, and COMMD1 interaction. None of the analyzed metabolites were effective as CIGB‐552 in eliciting apoptosis, cell‐penetrating capacity, and COMMD‐1 interaction. CIGB‐552 has the minimum peptide functional unit necessary to exert its anticancer activity.