Antimicrobial Peptides E-Book

David A. Phoenix

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 528

Veröffentlichungsjahr: 2012

Beschreibung

In this text, the small team of expert authors presents the field in a comprehensive and accessible manner that is well suited for students and junior researchers.

The result is a highly readable and systematically structured introduction to antimicrobial peptides, their structure, biological function and mode of action. The authors point the way towards a rational design of this potentially highly effective new class of clinical antibiotics on the brink of industrial application. They do this by discussing their design principles, target membranes and structure-activity relationships. The final part of the book describes recent successes in the application of peptides as anticancer agents.

Leseprobe

Table of Contents

Cover

Related Titles

Title page

Copyright page

Preface

List of Abbreviations

1 Antimicrobial Peptides: Their History, Evolution, and Functional Promiscuity

1.1 Introduction: The History of Antimicrobial Peptides

1.2 AMPs: Evolutionarily Ancient Molecules

1.3 AMPs: Multifunctional Molecules

1.4 Discussion

2 Cationic Antimicrobial Peptides

2.1 Introduction

2.2 CAMPs and Their Antimicrobial Action

2.3 CAMPs That Adopt an α-Helical Structure

2.4 CAMPs That Adopt a β-Sheet Structure

2.5 CAMPs That Adopt Extended Structures Rich in Specific Residues

2.6 Discussion

3 Anionic Antimicrobial Peptides

3.1 Introduction

3.2 AAMPs in the Respiratory Tract

3.3 AAMPs in the Brain

3.4 AAMPs in the Epidermis

3.5 AAMPs in the Epididymis

3.6 AAMPs in Blood Components

3.7 AAMPs in the Gastrointestinal Tract and Food Proteins

3.8 AAMPs and Their Structure–Function Relationships

3.9 Discussion

4 Graphical Techniques to Visualize the Amphiphilic Structures of Antimicrobial Peptides

4.1 Introduction

4.2 Amphiphilic Structures Adopted by AMPs

4.3 Qualitative Methods for Identifying Amphiphilic Structure

4.4 Quantitative Techniques for Analyzing Amphiphilic Structure

4.5 Discussion

5 Models for the Membrane Interactions of Antimicrobial Peptides

5.1 Introduction

5.2 CM-Associated Factors That Affect the Antimicrobial Action of α-CAMPs

5.3 Mechanisms Used by CAMPs for Microbial Membrane Interaction

5.4 Established Models for the Membrane Interactions of α-AMPs

5.5 Recent Novel Models for the Membrane Interactions of α-AMPs

5.6 Tilted Peptide Mechanism

5.7 Amyloidogenic Mechanisms

5.8 Discussion

6 Selectivity and Toxicity of Oncolytic Antimicrobial Peptides

6.1 Introduction

6.2 Peptide-Based Factors That Contribute to the Anticancer Action of Anticancer Peptides

6.3 Membrane-Based Factors That Contribute to the Anticancer Action of ACPs

6.4 Discussion

Index

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The Authors

Prof. David A. Phoenix

University of Central Lancashire

Pharmacy & Biomedical Sciences

Preston PR1 2HE

United Kingdom

Dr. Sarah R. Dennison

University of Central Lancashire

Pharmacy & Biomedical Sciences

Preston PR1 2HE

United Kingdom

Dr. Frederick Harris

University of Central Lancashire

School of Forensic and

Investigative Sciences

Preston PR1 2HE

United Kingdom

Cover design:

The cover shows aurein 2.3, a typical amphibian antimicrobial peptide in the presence of a lipid bilayer. The molecular dynamics simulation was undertaken by Dr. Manuela Mura, University of Central Lancashire. This MD simulation shows the potential of aurein 2.3 to use a pore-type mechanism of membrane interaction.

All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library.

Bibliographic information published by the Deutsche Nationalbibliothek

The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d-nb.de>.

© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

Composition Toppan Best-set Premedia Limited, Hong Kong

Cover Design Simone Benjamin, McLeese Lake

Print ISBN: 978-3-527-33263-2

ePDF ISBN: 978-3-527-65288-4

ePub ISBN: 978-3-527-65287-7

mobi ISBN: 978-3-527-65286-0

oBook ISBN: 978-3-527-65285-3

Preface

The indiscriminate and widespread use of antibiotics for both medical and non-medical purposes [1] has led to the emergence of pathogenic bacteria with multidrug resistance, with reports of these pathogens increasing at an alarming rate [2, 3]. This is especially true in the hospital environment where microbes with resistance towards conventional antibiotics are becoming increasingly common [4, 5], with recent high-profile examples including vancomycin-resistant enterococci [6] and methicillin-resistant Staphylococcus aureus (MRSA) [7]. There is clearly an urgent need for new antibiotics with novel mechanisms of antimicrobial action and the focus of this book is antimicrobial peptides (AMPs), which show high potential to serve in this capacity. In Chapter 1 we chart the discovery of AMPs, which is generally taken as the late 1980s when major research on these peptides began. This research revealed that AMPs are evolutionarily ancient molecules that are endogenous antibiotics produced by nearly all living organisms. However, it is now also becoming clear that in addition to their antimicrobial function, AMPs serve a variety of other roles, including modulation of the innate and adaptive immune systems via their ability to function as chemotactic agents. Over 2000 AMPs are now known and characterization has shown that the vast majority of these peptides are cationic, which are discussed in Chapter 2, while the remaining AMPs are generally anionic and are considered in Chapter 3. These chapters show that the capacity of AMPs to kill microbes depends upon a number of their structural and physiochemical characteristics such as charge and amphiphilicity, which facilitates their ability to partition into the membranes of the target organism. In most cases, this action leads to membrane permeabilization and death of the host microbe, although in some cases AMPs are translocated across the membrane to attack intracellular targets such as DNA.

The most researched AMPs are those that form α-helices (α-AMPs), which may be their inherent secondary structure, although in most cases these peptides are unfolded in solution and require the membrane interface to adopt α-helical conformations. These α-helices are generally amphiphilic, which allows the apolar face of the peptide to interact with the membrane hydrophobic core while concomitantly permitting its polar face to engage in electrostatic interactions with the membrane lipid head-group region [8]. Based on the spatial regularity of the residues within these amphiphilic structures, a number of techniques have been developed that can predict the potential of peptides to form membrane interactive α-AMPs [9, 10]. A number of prediction techniques for other types of AMPs have also been presented [11, 12] and an overview of this area of research is discussed in Chapter 4.

In addition to peptide-based properties, a number of membrane-based factors also contribute to the ability of AMPs to interact with membranes. Major examples of these factors include the transmembrane potential, lipid-packing characteristics, and the net negative charge generally carried by microbial membranes, which are targeted by cationic AMPs and thereby play fundamental roles in both the activity and selectivity of these peptides. Based on this research, a number of models to describe the antimicrobial activity of these peptides have been proposed, which are discussed in Chapter 5. In addition, these models appear to describe the ability of AMPs to target and kill cancer cells, the membranes of which also carry a net negative charge, which is discussed in Chapter 6. Currently, there is currently little evidence of microbial resistance to AMPs [13] and, taken with the research described in the foregone chapters, this has led to the view that AMPs are attractive propositions as lead compounds to serve in a number of scenarios [14]. Major examples of this use include the treatment of cancer [15], along with infection control in the food industry, agriculture [16, 17], and healthcare [5, 18–20]. For example, the fungal defensin, plectasin, and its derivative, NZ2114, are currently under development by Novozymes as lead compounds for use against MRSA and S. aureus with resistance to vancomycin [21].

Although much has been learnt about AMPs and their various biological roles since they were first discovered, the factors underpinning their microbial selectivity and toxicity are still poorly understood. In a sense, the antimicrobial mechanisms of these peptides draw parallels to the “lock and key” model postulated for enzyme activity [22], where the “key” refers to characteristics of the peptide and the “lock” refers to those of the target membrane. For the action of AMPs to occur efficiently, the “lock” and “key” need to be fully engaged, and it is hoped that the discussion of these peptides and our current understanding of their function will further stimulate research into fully elucidating these structure–function relationships as well as draw attention to the importance of AMPs in the pharmaceutical industry.

University of Central Lancashire, Preston, UK

November 2012

David A. Phoenix

Sarah R. Dennison

Frederick Harris

References

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2 Arias, C.A. and Murray, B.E. (2009) Antibiotic-resistant bugs in the 21st century – a clinical super-challenge. The New England Journal of Medicine, 360, 439–443.

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6 Arias, C.A. and Murray, B.E. (2012) The rise of the Enterococcus: beyond vancomycin resistance. Nature Reviews Microbiology, 10, 266–278.

7 Gould, I.M., David, M.Z., Esposito, S., Garau, J., Lina, G., Mazzei, T., and Peters, G. (2012) New insights into methicillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance. International Journal of Antimicrobial Agents, 39, 96–104.

8 Pasupuleti, M., Schmidtchen, A., and Malmsten, M. (2012) Antimicrobial peptides: key components of the innate immune system. Critical Reviews in Biotechnology, 32, 143–171.

9 Phoenix, D.A. and Harris, F. (2002) The hydrophobic moment and its use in the classification of amphiphilic structures [review]. Molecular Membrane Biology, 19, 1–10.

10 Phoenix, D.A., Harris, F., Daman, O.A., and Wallace, J. (2002) The prediction of amphiphilic alpha-helices. Current Protein & Peptide Science, 3, 201–221.

11 Porto, W.F., Silva, O.N., and Franco, O. (2012) Prediction and rational design of antimicrobial peptides, in Protein Structure (ed. E. Faraggi), InTech, New York, pp. 377–396.

12 Juretic, D., Vukicevic, D., Petrov, D., Novkovic, M., Bojovic, V., Lucic, B., Ilic, N., and Tossi, A. (2011) Knowledge-based computational methods for identifying or designing novel, non-homologous antimicrobial peptides. European Biophysics Journal with Biophysics Letters, 40, 371–385.

13 Peschel, A. and Sahl, H.-G. (2006) The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nature Reviews Microbiology, 4, 529–536.

14 Hadley, E.B. and Hancock, R.E.W. (2010) Strategies for the discovery and advancement of novel cationic antimicrobial peptides. Current Topics in Medicinal Chemistry, 10, 1872–1881.

15 Ashley, L.H., Melanie, R.P.C., and David, W.H. (2012) Obstacles and solutions to the use of cationic antimicrobial peptides in the treatment of cancer, in Small Wonders: Peptides for Disease Control (ed. K. Rajasekaran, J.W. Cary, J. Jaynes, and E. Montesinos), American Chemical Society, Washington, DC, pp. 61–78.

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List of Abbreviations

α-ACPIACP with inactivity against cancer cells[G–]Active against Gram negative bacteria[G+, G–]Active against Gram positive and Gram negative bacteria[G+, G–, F]Active against Gram positive and Gram negative bacteria and fungi[G+]Active against Gram positive bacteriaASPagouti signal peptideα-MSHalpha-melanocyte stimulating hormoneADAlzheimer’s DiseaseACEangiotensin converting enzymeAAMPsAnionic antimicrobial proteins and peptidesACPsAnticancer peptidesAPCsantigen-presenting cellsAMPsAntimicrobial peptidesANNArtificial neural networksATDAtopic dermatitisα-ACPsα-helical anticancer peptidesα-AMPsα-helical antimicrobial peptidesα-CAMPsα-helical cationic antimicrobial peptidesα-LAα-lactalbuminALA5-aminolevulinic acidBDsBig defensinsβ-LGβ-lactoglobulinβ-ACPsβ-sheet anticancer peptidesβ-CAMPsβ-sheet cationic antimicrobial peptidesCLCardiolipinCAMPsCationic antimicrobial peptidesCVCCentral venous cathetersCTChemotherapyCSChondroitin sulfateCFCystic fibrosisCMCytoplasmic membranesDCsDendritic cellsDCDDermcidinEGFepidermal growth factorE-ACPsextended structuresEPSExtracellular polymeric substanceFPAfibrinopeptide AFPBfibrinopeptide BFDAFood and Drug Administration<μG>Glycine momentGAGGlycosaminoglycan[G+, G−, F, P]    Gram positive and Gram negative bacteria, and fungi and parasitesGPCRG-protein-coupled receptorHSHeparan sulfateHMMsHidden Markov modelsHBDsHuman β-defensinsHIVHuman immunodeficiency virus<μH>Hydrophobic moment<H>HydrophobicityHAshylids of AustraliaIFSIncremental feature selectionACPAOIneffective against non-cancerous cells and erythrocytesLFMLactoferricinLD50lethal dose 50%LPSLipopolysaccharideLPCLysophosphatidylcholineLysylPGLysylated PGMIP-3αmacrophage inflammatory protein-3αMc1rmelanocortin 1 receptorM-enkmethionineenkephalinM-enk-RFmethionine-enkephalin-arginine phenylalanineMRSAMethicillin-resistant Staphylococcus aureusMICsMinimum inhibition concentrationmRMMinimum redundancy methodMDMolecular dynamicsMHPMolecular hydrophobic potentialMLPMolecular lipophilic potentialMDRMulti-drug resistantMDRPAMultidrug-resistant Pseudomonas aeroginosaPR-CAMPsmultiple arginine residues-CAMPsMyD88myeloid differentiation primary response gene 88NEPneutral endopeptidaseOMOuter membraneOAOvalbuminPLUNCPalate, lung, nasal epithelium clonePCPhosphatidylcholinePEPhosphatidylethanolaminePGPhosphatidylglycerolPIPhosphatidylinositolPSPhosphatidylserinePACTPhotodynamic antimicrobial chemotherapyPLSPrinciple latent structuresPCAPrincipal component analysisPEAProenkephalin APGsProteoglycansQSARQuantitative structure activity relationshipsRTRadiation therapyRANAEsranids from Asia, North America, and EuropeRBD3rat β-defensin 3ROSreactive oxygen speciesSHMShai, Huang and MatsazukiSPSphingomyelinSARStructure-activity relationshipsSAAPsSurfactant-associated anionic peptidesTLRsToll-like receptorsACPTToxic to both cancerous and non-cancerous cellsTMTransmembraneΔψTransmembrane potentialTA-CAMPstryptophan and arginine residues-CAMPsWHOWorld Health Organization