Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download The Mechanism Of Lipid Bilayer Disruption By The Human Antimicrobial Peptide Ll 37 PDF full book. Access full book title The Mechanism Of Lipid Bilayer Disruption By The Human Antimicrobial Peptide Ll 37.
| Author | : Katherine Anne Henzler Wildman |
| Publisher | : |
| Total Pages | : 660 |
| Release | : 2003 |
| Genre | : |
| ISBN | : |
| Author | : Claudia Dannehl |
| Publisher | : |
| Total Pages | : 0 |
| Release | : 2013 |
| Genre | : |
| ISBN | : |
A detailed description of the characteristics of antimicrobial peptides (AMPs) is highly demanded, since the resistance against traditional antibiotics is an emerging problem in medicine. They are part of the innate immune system in every organism, and they are very efficient in the protection against bacteria, viruses, fungi and even cancer cells. Their advantage is that their target is the cell membrane, in contrast to antibiotics which disturb the metabolism of the respective cell type. This allows AMPs to be more active and faster. The lack of an efficient therapy for some cancer types and the evolvement of resistance against existing antitumor agents make AMPs promising in cancer therapy besides being an alternative to traditional antibiotics. The aim of this work was the physical-chemical characterization of two fragments of LL-37, a human antimicrobial peptide from the cathelicidin family. The fragments LL-32 and LL-20 exhibited contrary behavior in biological experiments concerning their activity against bacterial cells, human cells and human cancer cells. LL-32 had even a higher activity than LL-37, while LL-20 had almost no effect. The interaction of the two fragments with model membranes was systematically studied in this work to understand their mode of action. Planar lipid films were mainly applied as model systems in combination with IR-spectroscopy and X-ray scattering methods. Circular Dichroism spectroscopy in bulk systems completed the results. In the first approach, the structure of the peptides was determined in aqueous solution and compared to the structure of the peptides at the air/water interface. In bulk, both peptides are in an unstructured conformation. Adsorbed and confined to at the air-water interface, the peptides differ drastically in their surface activity as well as in the secondary structure. While LL-32 transforms into an [alpha]-helix lying flat at the water surface, LL-20 stays partly unstructured. This is in good agreement with the high antimicrobial activity of LL-32. In the second approach, experiments with lipid monolayers as biomimetic models for the cell membrane were performed. It could be shown that the peptides fluidize condensed monolayers of negatively charged DPPG which can be related to the thinning of a bacterial cell membrane. An interaction of the peptides with zwitterionic PCs, as models for mammalian cells, was not clearly observed, even though LL-32 is haemolytic. In the third approach, the lipid monolayers were more adapted to the composition of human erythrocyte membranes by incorporating sphingomyelin (SM) into the PC monolayers. Physical-chemical properties of the lipid films were determined and the influence of the peptides on them was studied. It could be shown that the interaction of the more active LL-32 is strongly increased for heterogeneous lipid films containing both gel and fluid phases, while the interaction of LL-20 with the monolayers was unaffected. The results indicate an interaction of LL-32 with the membrane in a detergent-like way. Additionally, the modelling of the peptide interaction with cancer cells was performed by incorporating some negatively charged lipids into the PC/SM monolayers, but the increased charge had no effect on the interaction of LL-32. It was concluded, that the high anti-cancer activity of the peptide originates from the changed fluidity of cell membrane rather than from the increased surface charge. Furthermore, similarities to the physical-chemical properties of melittin, an AMP from the bee venom, were demonstrated.
| Author | : Sidney A. Simon |
| Publisher | : Academic Press |
| Total Pages | : 606 |
| Release | : 2002-11-13 |
| Genre | : Science |
| ISBN | : 0080925855 |
This volume contains a comprehensive overview of peptide-lipid interactions by leading researchers. The first part covers theoretical concepts, experimental considerations, and thermodynamics. The second part presents new results obtained through site-directed EPR, electron microscopy, NMR, isothermal calorimetry, and fluorescence quenching. The final part covers problems of biological interest, including signal transduction, membrane transport, fusion, and adhesion. Key Features * world-renowned experts * state-of-the-art experimental methods * monolayers, bilayers, biological membranes * theoretical aspects and computer simulations * rafts * synaptic transmission * membrane fusion * signal transduction
| Author | : Katsumi Matsuzaki |
| Publisher | : Springer |
| Total Pages | : 304 |
| Release | : 2019-04-12 |
| Genre | : Medical |
| ISBN | : 9811335885 |
This book presents an overview of antimicrobial peptides (AMPs), their mechanisms of antimicrobial action, other activities, and various problems that must still be overcome regarding their clinical application. Divided into four major parts, the book begins with a general overview of AMPs (Part I), and subsequently discusses the various mechanisms of antimicrobial action and methods for researching them (Part 2). It then addresses a range of activities other than antimicrobial action, such as cell penetration, antisepsis, anticancer, and immunomodulatory activities (Part 3), and explores the prospects of clinical application from various standpoints such as the selective toxicity, design, and discovery of AMPs (Part 4). A huge number of AMPs have been discovered in plants, insects, and vertebrates including humans, and constitute host defense systems against invading pathogenic microorganisms. Consequently, many attempts have been made to utilize AMPs as antibiotics. AMPs could help to solve the urgent problem of drug-resistant bacteria, and are also promising with regard to sepsis and cancer therapy. Gathering a wealth of information, this book will be a bible for all those seeking to develop antibiotics, anti-sepsis, or anticancer agents based on AMPs.
| Author | : Ales Iglic |
| Publisher | : Academic Press |
| Total Pages | : 358 |
| Release | : 2012-09-04 |
| Genre | : Medical |
| ISBN | : 0123965349 |
Advances in Planar Lipid Bilayers and Liposomes volumes cover a broad range of topics, including main arrangements of the reconstituted system, namely planar lipid bilayers as well as spherical liposomes. The invited authors present the latest results of their own research groups in this exciting multidisciplinary field. Incorporates contributions from newcomers and established and experienced researchers Explores the planar lipid bilayer systems and spherical liposomes from both theoretical and experimental perspectives Serves as an indispensable source of information for new scientists
| Author | : Stefania Piantavigna |
| Publisher | : |
| Total Pages | : 738 |
| Release | : 2014 |
| Genre | : |
| ISBN | : |
The emergence of bacteria that have developed resistance towards "traditional" antibiotics is becoming a serious global health threat. Consequently, alternative approaches are needed to find new drugs that can act directly as antibiotics or to assist traditional drugs to improve efficacy. The emergence of antimicrobial peptides (AMPs) as a possible new class offers promise. AMPs represent a large and varied group of "natural antibiotics" present in virtually every organism. However, in order to develop new drugs derived from AMPs knowledge of the bioactivity of these is needed, such as concentration ranges and specific bacterial targets. Of great practical importance is to have a comprehensive understanding of the mechanism of action of AMPs, so that the risk of cross-reactivity and development of new bacterial resistance is minimised. All AMPs interact with the cell membrane, which is a complex and dynamic system, mostly containing phospholipids and proteins. Phospholipids are not simple "bricks" of the membrane, but they themselves are involved in various cellular processes. Therefore, biomimetic membranes, e.g. supported lipid bilayers (SLBs), represent a valid approach for investigating the interactions between lipids and AMPs. Creation of a supported membrane reduces the complexity of those studies to just one variable. Many variables influence the formation of SLBs and a protocol regarding the formation of SLBs assembled on gold-coated sensors is described in Paper 1. The membrane deposition and the peptide-membrane interactions were investigated using a Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) (Paper 2). Thus, the action of various peptides were investigated with zwitterionic membranes, which contained negatively charged lipid (bacterial membranes), or cholesterol (mammalian membranes).The action of the two most widely studied AMPs, melittin and magainin 2, on SLBs, has been examined using QCM-D in Chapter 3. These peptides formed "toroidal pores", which lead to membrane disruption. However, the action of these peptides has been found to be both concentration and composition dependent.Many AMPs are enriched in a particular amino acid residue. The influence of several of these peptide residues has been investigated using QCM-D in Chapters 4, 5 and 6. The action of proline-rich peptides apidaecins HbI and HbII, the variant Api88 and oncocin peptides on SLBs, are illustrated in Papers 3, 4 and 5, respectively. These peptides were found to insert into the membrane without any evidence of disruption. The influence of lipid composition on the activity of the arginine-rich peptide Tat has also been investigated with QCM together with scanning electrochemical microscopy (SECM) (Chapter 5). The cell-penetrating Tat peptide was shown to act as a lytic AMP in the presence of negatively charged membranes (Papers 6 and 7).The addition of tryptophan residues in the sequence of a short arginine-rich peptide, (RW)3, caused a dramatic switch from cell penetrating to lytic activity, while the inclusion of ruthenocene in the peptide RcCO-W(RW)2 did not affect the peptide activity (Chapter 6).Finally, in Chapter 7, Uperin 3.5, an amyloid-like AMP, demonstrated that the amyloid fibrils are not necessary for the membrane-disruption. However, the action of Uperin 3.5 towards zwitterionic membranes is switched to insertion if cholesterol is present in the membrane. Thus, QCM has been demonstrated to be an invaluable technique for characterising, in real time, the action of various peptides on SLBs of bacterial mimetic composition and mammalian. However, the combination of QCM with other techniques e.g. SECM, is always encouraged to reinforce this data and to gain a wide perspective of activity.
| Author | : Kin Lok Lam |
| Publisher | : |
| Total Pages | : 410 |
| Release | : 2009 |
| Genre | : Lipids |
| ISBN | : |
| Author | : Robert B. Gennis |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 549 |
| Release | : 2013-04-17 |
| Genre | : Science |
| ISBN | : 1475720653 |
New textbooks at all levels of chemistry appear with great regularity. Some fields like basic biochemistry, organic reaction mechanisms, and chemical thermody namics are well represented by many excellent texts, and new or revised editions are published sufficiently often to keep up with progress in research. However, some areas of chemistry, especially many of those taught at the graduate level, suffer from a real lack of up-to-date textbooks. The most serious needs occur in fields that are rapidly changing. Textbooks in these subjects usually have to be written by scientists actually involved in the research which is advancing the field. It is not often easy to persuade such individuals to set time aside to help spread the knowledge they have accumulated. Our goal, in this series, is to pinpoint areas of chemistry where recent progress has outpaced what is covered in any available textbooks, and then seek out and persuade experts in these fields to produce relatively concise but instructive introductions to their fields. These should serve the needs of one semester or one quarter graduate courses in chemistry and biochemistry. In some cases, the availability of texts in active research areas should help stimulate the creation of new courses.
| Author | : David A. Phoenix |
| Publisher | : John Wiley & Sons |
| Total Pages | : 0 |
| Release | : 2013-04-01 |
| Genre | : Science |
| ISBN | : 9783527332632 |
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.
| Author | : |
| Publisher | : |
| Total Pages | : 0 |
| Release | : 2014 |
| Genre | : |
| ISBN | : |
Antimicrobial peptides are a class of compounds with broad-spectrum antibacterial activity, found in several different species. While there has been considerable research on these peptides, both on live bacteria and on model lipid bilayers, the details of their mechanism of action is still a mystery. We present time-lapse, single cell fluorescence microscopy data on the model Gram-positive bacterium Bacillus subtilis exposed to the antimicrobial peptides LL-37 and alamethicin. Our technique allows simultaneous measurement of cell growth, cell envelope permeability, and the pH component of the proton motive force on individual cells. Exposure to either LL-37 or alamethicin leads to the permeabilization of the cytoplasmic membrane, which occurs simultaneously with nucleoid staining by Sytox Green/Orange, and abrupt cell shrinkage. The cells become permeable to larger species like GFP at longer times of exposure, and eventually lyse. While both peptides show similarities, important differences are seen by comparing the staining dynamics of the DNA stains Sytox Green/Orange. LL-37 shows evidence for localized membrane permeabilization, while alamethicin does not. Our data sheds light on the exact symptoms and mechanisms of antimicrobial stress.
