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      Characterization of Antimicrobial Peptides toward the Development of Novel Antibiotics

      review-article
      1 , 2 , 3 , 2 , *
      Pharmaceuticals
      MDPI
      antibiotic, antimicrobial peptide, drug delivery, activity regulation

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          Abstract

          Antimicrobial agents have eradicated many infectious diseases and significantly improved our living environment. However, abuse of antimicrobial agents has accelerated the emergence of multidrug-resistant microorganisms, and there is an urgent need for novel antibiotics. Antimicrobial peptides (AMPs) have attracted attention as a novel class of antimicrobial agents because AMPs efficiently kill a wide range of species, including bacteria, fungi, and viruses, via a novel mechanism of action. In addition, they are effective against pathogens that are resistant to almost all conventional antibiotics. AMPs have promising properties; they directly disrupt the functions of cellular membranes and nucleic acids, and the rate of appearance of AMP-resistant strains is very low. However, as pharmaceuticals, AMPs exhibit unfavorable properties, such as instability, hemolytic activity, high cost of production, salt sensitivity, and a broad spectrum of activity. Therefore, it is vital to improve these properties to develop novel AMP treatments. Here, we have reviewed the basic biochemical properties of AMPs and the recent strategies used to modulate these properties of AMPs to enhance their safety.

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          Most cited references139

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          Defensins: antimicrobial peptides of innate immunity.

          Tomas Ganz (2003)
          The production of natural antibiotic peptides has emerged as an important mechanism of innate immunity in plants and animals. Defensins are diverse members of a large family of antimicrobial peptides, contributing to the antimicrobial action of granulocytes, mucosal host defence in the small intestine and epithelial host defence in the skin and elsewhere. This review, inspired by a spate of recent studies of defensins in human diseases and animal models, focuses on the biological function of defensins.
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            The expanding scope of antimicrobial peptide structures and their modes of action.

            Antimicrobial peptides (AMPs) are an integral part of the innate immune system that protect a host from invading pathogenic bacteria. To help overcome the problem of antimicrobial resistance, cationic AMPs are currently being considered as potential alternatives for antibiotics. Although extremely variable in length, amino acid composition and secondary structure, all peptides can adopt a distinct membrane-bound amphipathic conformation. Recent studies demonstrate that they achieve their antimicrobial activity by disrupting various key cellular processes. Some peptides can even use multiple mechanisms. Moreover, several intact proteins or protein fragments are now being shown to have inherent antimicrobial activity. A better understanding of the structure-activity relationships of AMPs is required to facilitate the rational design of novel antimicrobial agents. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              The co-evolution of host cationic antimicrobial peptides and microbial resistance.

              Endogenous cationic antimicrobial peptides (CAMPs) are among the most ancient and efficient components of host defence. It is somewhat of an enigma that bacteria have not developed highly effective CAMP-resistance mechanisms, such as those that inhibit many therapeutic antibiotics. Here, we propose that CAMPs and CAMP-resistance mechanisms have co-evolved, leading to a transient host-pathogen balance that has shaped the existing CAMP repertoire. Elucidating the underlying principles of this process could help in the development of more sustainable antibiotics.
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                Author and article information

                Journal
                Pharmaceuticals (Basel)
                Pharmaceuticals (Basel)
                pharmaceuticals
                Pharmaceuticals
                MDPI
                1424-8247
                21 August 2013
                August 2013
                : 6
                : 8
                : 1055-1081
                Affiliations
                [1 ]Japan Society for Promotion of Science, Sakyo-ku, Kyoto 606-8502, Japan; E-Mail: w-aoki@ 123456ap.eng.osaka-u.ac.jp
                [2 ]Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
                [3 ]Department of Applied Physics, Division of Precision Science & Applied Physics, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: miueda@ 123456kais.kyoto-u.ac.jp ; Tel.: +81-(0)75-753-6110; Fax: +81-(0)75-753-6112.
                Article
                pharmaceuticals-06-01055
                10.3390/ph6081055
                3817730
                24276381
                08b03259-6a68-4d1c-9dd8-03d8fe2c484e
                © 2013 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 16 July 2013
                : 02 August 2013
                : 16 August 2013
                Categories
                Review

                antibiotic,antimicrobial peptide,drug delivery,activity regulation

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