In this book, a summary and update of the most important areas of CPP research are presented, whilst raising relevant questions for further development. The CPP sequences are presented and discussed throughout the book. The methods for testing CPP mechanisms are discussed in detail. Various approaches for the testing of endocytotic pathways of CPP uptake are also described. Different CPP uptake experiments are compared since it is becoming clear that it is often best to apply several methods in a complementary manner in order to most comprehensively evaluate CPP uptake mechanisms due to the complexity of these processes. A brief summary of functionality issues of CPPs, both in vitro and in vivo are discussed. Therapeutic potential of CPPs and commercial developments are discussed. The monograph is written for researchers and students in the field.

Divided into three parts this volume summarizes the most important areas of Cell-Penetrating Peptides (CPP) research . Part one briefly presents the historical background of CPP studies and the classifications of the available CPPs, and then summarizes the approaches for prediction of novel CPPs. Part two mainly describes the methods for studies of “naked” CPPs, that is, CPPs without conjugated cargos. Last but not least part three presents a representative and brief summary of functionality issues of CPPs, both in vitro and in vivo. As a volume in the highly successful Methods in Molecular Biology series, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Concise and easy-to-use, Cell-Penetrating Peptides: Methods and Protocols, Second Edition hopes to raise relevant questions for further development.

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.

This book features a special subsection of Nanomedicine, an application of nanotechnology to achieve breakthroughs in healthcare. It exploits the improved and often novel physical, chemical and biological properties of materials only existent at the nanometer scale. As a consequence of small scale, nanosystems in most cases are efficiently uptaken by cells and appear to act at the intracellular level. Nanotechnology has the potential to improve diagnosis, treatment and follow-up of diseases, and includes targeted drug delivery and regenerative medicine; it creates new tools and methods that impact significantly upon existing conservative practices. This volume is a collection of authoritative reviews. In the introductory section we define the field (intracellular delivery). Then, the fundamental routes of nanodelivery devices, cellular uptake, types of delivery devices, particularly in terms of localized cellular delivery, both for small drug molecules, macromolecular drugs and genes; at the academic and applied levels, are covered. The following section is dedicated to enhancing delivery via special targeting motifs followed by the introduction of different types of intracellular nanodelivery devices (e.g. a brief description of their chemistry) and ways of producing these different devices. Finally, we put special emphasis on particular disease states and on other biomedical applications, whilst diagnostic and sensing issues are also included. Intracellular delivery / therapy is a highly topical which will stir great interest. Intracellular delivery enables much more efficient drug delivery since the impact (on different organelles and sites) is intracellular as the drug is not supplied externally within the blood stream. There is great potential for targeted delivery with improved localized delivery and efficacy.

DNA delivery into cells is a rapidly developing area in gene therapy and biotechnology. Moreover, it is a powerful research tool to determine gene structure, regulation, and function. Viral methods of DNA delivery are well-characterized and efficient, but little is known about the toxicity and immunogenecity of viral vectors. As a result, non-viral, transfection methods of DNA delivery are of increasing interest. Synthetic DNA Delivery Systems is a comprehensive and current resource on DNA transfection. The use of histidine-rich peptides and polypeptides as DNA delivery systems and self-assembled delivery systems based on cationic lipids and polymers are discussed. Targeted delivery to organelles, tumor cells and dendritic cells comprise an important topic.

Therapeutic Proteins and Peptides, Volume 112 in an ongoing series promotes further research in the discovery of new therapeutic targets that can be affected by therapeutic proteins and peptides to cure or manage symptoms of human diseases, with this release focusing on the Rational Design of Stable Liquid Formulations of Biopharmaceuticals, Formulation strategies for peptides, proteins and antibodies using nanotechnology, the Solution structural dynamics of therapeutic peptides and their adsorption on plasmonic nanoparticles, Enzymatic approaches of protein-polymer conjugation, Chimeric small antibody fragments as a strategy to deliver therapeutic payloads, Smart cell-penetrating peptide-based techniques for cytoplasmic delivery of therapeutic macromolecules, and more. - Describes advances in the discovery and application of therapeutic proteins/peptides which allow better targeting to the site of treatment and cause fewer adverse effects when compared to chemical compounds used for disease treatment - Targeted to a very wide audience of specialists, researchers and students - Written by well-renown authorities in their field - Includes a number of high quality illustrations, figures and tables

The state of the art in biopharmaceutical FUSION PROTEIN DESIGN Fusion proteins belong to the most lucrative biotech drugs—with Enbrel® being one of the best-selling biologics worldwide. Enbrel® represents a milestone of modern therapies just as Humulin®, the first therapeutic recombinant protein for human use, approved by the FDA in 1982 and Orthoclone® the first monoclonal antibody reaching the market in 1986. These first generation molecules were soon followed by a plethora of recombinant copies of natural human proteins, and in 1998, the first de novo designed fusion protein was launched. Fusion Protein Technologies for Biopharmaceuticals examines the state of the art in developing fusion proteins for biopharmaceuticals, shedding light on the immense potential inherent in fusion protein design and functionality. A wide pantheon of international scientists and researchers deliver a comprehensive and complete overview of therapeutic fusion proteins, combining the success stories of marketed drugs with the dynamic preclinical and clinical research into novel drugs designed for as yet unmet medical needs. The book covers the major types of fusion proteins—receptor-traps, immunotoxins, Fc-fusions and peptibodies—while also detailing the approaches for developing, delivering, and improving the stability of fusion proteins. The main body of the book contains three large sections that address issues key to this specialty: strategies for extending the plasma half life, the design of toxic proteins, and utilizing fusion proteins for ultra specific targeting. The book concludes with novel concepts in this field, including examples of highly relevant multifunctional antibodies. Detailing the innovative science, commercial realities, and brilliant potential of fusion protein therapeutics, Fusion Protein Technologies for Biopharmaceuticals is a must for pharmaceutical scientists, biochemists, medicinal chemists, molecular biologists, pharmacologists, and genetic engineers interested in determining the shape of innovation in the world of biopharmaceuticals.

This book covers the most up-to-date photoaffinity labeling method to tackle the key loop module involved in the binding process of a bioactive small molecule to its host protein. The book introduces rational points for preparing powerful photoaffinity probes, keys for the efficient analysis of labeled products, and recent successful applications for protein probing. Regarding drug design, the unique topics of the book are the special consideration of the crosslinking potential of recent probes and their application of important receptor proteins . This book presents emerging technologies of photoaffinity labeling to readers who are working in the fields of proteomics, molecular recognition, and drug discovery and development.

Solid-binding peptides have been used increasingly as molecular building blocks in nanobiotechnology as they can direct the assembly and functionalisation of a diverse range of materials and have the ability to regulate the synthesis of nanoparticles and complex nanostructures. Nanostructured materials such as β-sheet fibril-forming peptides and α-helical coiled coil systems have displayed many useful properties including stimulus-responsiveness, modularity and multi-functionality, providing potential technological applications in tissue engineering, antimicrobials, drug delivery and nanoscale electronics. The current situation with respect to self-assembling peptides and bioactive matrices for regenerative medicine are reviewed, as well as peptide-target modeling and an examination of future prospects for peptides in these areas.

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