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      Peptides with Dual Antimicrobial and Anticancer Activities

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          Abstract

          In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of cancer, due to the instability in the immune system that allows cancer cells to proliferate. Likewise, the physical debility associated with cancer or with anticancer therapy itself often paves the way for opportunistic infections. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Highly cationic and amphipathic, they have demonstrated efficacy against both conditions, with the number of nature-driven or synthetically designed peptides increasing year by year. With similar properties, AMPs that can also act as ACPs are viewed as future chemotherapeutic drugs, with the advantage of low propensity to resistance, which started this paradigm in the pharmaceutical market. These peptides have already been described as molecules presenting killing mechanisms at the membrane level, but also acting toward intracellular targets, which increases their success compartively to one-target specific drugs. This review will approach the desirable characteristics of small peptides that demonstrated dual activity against microbial infections and cancer, as well as the peptides engaged in clinical trials.

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          Most cited references54

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          Antibiotic-resistant bugs in the 21st century--a clinical super-challenge.

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            Peptide antibiotics.

            R. Hancock (1997)
            The era of the "classical antibiotic" may be over. The emergence of resistance has seen to that. Yet no truly novel class of antibacterial agent has come on the market in the past 30 years. Currently there is great interest in peptide antibiotics, especially the cationic peptides. Thousands of such molecules have been synthesised and just a few are entering clinical trials. Because they kill bacteria quickly by the physical disruption of cell membranes, peptide antibiotics may not face the rapid emergence of resistance.
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              Mechanism of action of the antimicrobial peptide buforin II: buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functions.

              The mechanism of action of buforin II, which is a 21-amino acid peptide with a potent antimicrobial activity against a broad range of microorganisms, was studied using fluorescein isothiocyanate (FITC)-labeled buforin II and a gel-retardation experiment. Its mechanism of action was compared with that of the well-characterized magainin 2, which has a pore-forming activity on the cell membrane. Buforin II killed Esche-richia coli without lysing the cell membrane even at 5 times minimal inhibitory concentration (MIC) at which buforin II reduced the viable cell numbers by 6 orders of magnitude. However, magainin 2 lysed the cell to death under the same condition. FITC-labeled buforin II was found to penetrate the cell membrane and accumulate inside E. coli even below its MIC, whereas FITC-labeled magainin 2 remained outside or on the cell wall even at its MIC. The gel-retardation experiment showed that buforin II bound to DNA and RNA of the cells over 20 times strongly than magainin 2. All these results indicate that buforin II inhibits the cellular functions by binding to DNA and RNA of cells after penetrating the cell membranes, resulting in the rapid cell death, which is quite different from that of magainin 2 even though they are structurally similar: a linear amphipathic alpha-helical peptide.
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                Author and article information

                Contributors
                Journal
                Front Chem
                Front Chem
                Front. Chem.
                Frontiers in Chemistry
                Frontiers Media S.A.
                2296-2646
                21 February 2017
                2017
                : 5
                : 5
                Affiliations
                [1] 1Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa Lisbon, Portugal
                [2] 2S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco Campo Grande, Brazil
                [3] 3Programa de Pós-Graduação em Patologia Molecular, Universidade de Brasília Brasília, Brazil
                Author notes

                Edited by: Neil Martin O'Brien-Simpson, University of Melbourne, Australia

                Reviewed by: Yuji Nishiuchi, GlyTech, Inc., Japan; Jonathan Baell, Monash University, Australia

                *Correspondence: Octávio L. Franco ocfranco@ 123456gmail.com

                This article was submitted to Chemical Biology, a section of the journal Frontiers in Chemistry

                †Present Address: Octávio L. Franco, Pós-graduação em Ciências Genômicas e Biotecnologia, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasília, Brazil

                ‡These authors have contributed equally to this work.

                Article
                10.3389/fchem.2017.00005
                5318463
                28271058
                2744dcfd-7488-4637-bcd9-efc5abbd4ccb
                Copyright © 2017 Felício, Silva, Gonçalves, Santos and Franco.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 December 2016
                : 06 February 2017
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 75, Pages: 9, Words: 6097
                Categories
                Chemistry
                Mini Review

                anticancer peptides (acps),antimicrobial peptides (amps),cancer,multi-resistant infections,bacteria

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