Antimicrobial Peptides

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.

Preface IX List of Abbreviations XIII 1 Antimicrobial Peptides: Their History, Evolution, and Functional Promiscuity 1 Summary 1 1.1 Introduction: The History of Antimicrobial Peptides 1 1.2 AMPs: Evolutionarily Ancient Molecules 4 1.3 AMPs: Multifunctional Molecules 11 1.4 Discussion 17 References 19 2 Cationic Antimicrobial Peptides 39 Summary 39 2.1 Introduction 39 2.2 CAMPs and Their Antimicrobial Action 42 2.3 CAMPs That Adopt an α–Helical Structure 43 2.4 CAMPs That Adopt a β–Sheet Structure 51 2.5 CAMPs That Adopt Extended Structures Rich in Specific Residues 55 2.6 Discussion 60 References 62 3 Anionic Antimicrobial Peptides 83 Summary 83 3.1 Introduction 83 3.2 AAMPs in the Respiratory Tract 85 3.3 AAMPs in the Brain 87 3.4 AAMPs in the Epidermis 91 3.5 AAMPs in the Epididymis 94 3.6 AAMPs in Blood Components 96 3.7 AAMPs in the Gastrointestinal Tract and Food Proteins 97 3.8 AAMPs and Their Structure–Function Relationships 99 3.9 Discussion 101 References 102 4 Graphical Techniques to Visualize the Amphiphilic Structures of Antimicrobial Peptides 115 Summary 115 4.1 Introduction 115 4.2 Amphiphilic Structures Adopted by AMPs 116 4.3 Qualitative Methods for Identifying Amphiphilic Structure 118 4.4 Quantitative Techniques for Analyzing Amphiphilic Structure 121 4.5 Discussion 133 References 135 5 Models for the Membrane Interactions of Antimicrobial Peptides 145 Summary 145 5.1 Introduction 145 5.2 CM–Associated Factors That Affect the Antimicrobial Action of α–CAMPs 149 5.3 Mechanisms Used by CAMPs for Microbial Membrane Interaction 154 5.4 Established Models for the Membrane Interactions of α–AMPs 155 5.5 Recent Novel Models for the Membrane Interactions of α–AMPs 159 5.6 Tilted Peptide Mechanism 161 5.7 Amyloidogenic Mechanisms 163 5.8 Discussion 166 References 168 6 Selectivity and Toxicity of Oncolytic Antimicrobial Peptides 181 Summary 181 6.1 Introduction 181 6.2 Peptide–Based Factors That Contribute to the Anticancer Action of Anticancer Peptides 183 6.3 Membrane–Based Factors That Contribute to the Anticancer Action of ACPs 196 6.4 Discussion 205 References 207 Index 223

Professor David Andrew Phoenix, OBE, AcSS, DSc studied Biochemistry at degree and doctoral level at Liverpool University which in 2009 awarded him a Doctor of Science for his impact on the field. In 2000 he was appointed Professor of Biochemistry, at the University of Central Lancashire (UCLan) and has held visiting chairs in Canada and Russia. He has published over 150 papers as well as a number of edited collections and monographs. He is a Fellow of the Royal Society of Chemistry, The Society of Biology, The Institute of Mathematics and Its Applications and the Royal Society of Medicine. Since 2008 he has been the Deputy Vice Chancellor of UCLan and also Chairs a research institute in Shenzhen focused on nanotechnology and biomedical engineering. He was made an Officer of the Most Excellent Order of the British Empire in 2010 for services to Science and Higher Education and recognized as an Academician by the Academy of Social Sciences in 2012. Dr. Sarah Rachel Dennison PhD graduated from the University of Wales, Bangor with a Bachelor of Science in Environmental Biology in 1999. Subsequently, she undertook postgraduate research in Biochemistry / Biophysics, which led to a doctorate in 2004. Currently, Sarah is a Research Associate in the School of Pharmacy and Biomedical Sciences at UCLan where she is investigating the role of amphiphilicity in the function of antimicrobial peptides using a number of biophysical techniques. Dr. Frederick Harris PhD studied at UCLan, graduating with a Bachelor of Science in Biochemistry and Microbiology in 1993 before gaining his Doctorate for work on the penicillinbinding proteins of Escherichia coli in 1998. Subsequently, he has undertaken research at Utrecht University and the Leibniz–Centre for Medicine and Biosciences, Germany. In 2000, Frederick started as a Research Fellow at UCLan and now has more than 75 publications to his name, which primarily focus on antimicrobial and anticancer peptides.