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During the course of evolution, an imbalance was created between the rate of vertebrate genetic adaptation and that of the lower forms of living organisms, such as bacteria and viruses. This imbalance has given the latter the advantage of generating, relatively quickly, molecules with unexpected structures and features that carry a threat to vertebrates. To compensate for their weakness, vertebrates have accelerated their own evolutionary processes, not at the level of whole organism, but in specialized cells containing the genes that code for antibody molecules or for T-cell receptors. That is, when an immediate requirement for molecules capable of specific interactions arose, nature has preferred to speed up the mode of Darwinian evolution in pref- ence to any other approach (such as the use of X-ray diffraction studies and computergraphic analysis). Recently, Darwinian rules have been adapted for test tube research, and the concept of selecting molecules having particular characteristics from r- dom pools has been realized in the form of various chemical and biological combinatorial libraries. While working with these libraries, we noticed the interesting fact that when combinatorial libraries of oligopeptides were allowed to interact with different selector proteins, only the actual binding sites of these proteins showed binding properties, whereas the rest of the p- tein surface seemed "inert. " This seemingly common feature of protein- having no extra potential binding sites--was probably selected during evolution in order to minimize nonspecific interactions with the surrounding milieu.
In recent years, research has shown the importance of peptides in neuroscience, immunology, and cell biology. Active research programs worldwide are now engaged in developing peptide-based drugs and vaccines using modification of natural peptides and proteins, design of artificial peptides and peptide mimetics, and screening of peptide and phage libraries. In this comprehensive book, the authors discuss peptide synthesis and application within the context of their increasing importance to the pharmaceutical industry. Peptides: Synthesis, Structures, and Applications explores the broad growth of information in modern peptide synthetic methods and the structure-activity relationships of synthetic polypeptides. - The history of peptide chemistry - Amide formation, deprotection, and disulfide formation in peptide synthesis - Solid-phase peptide synthesis - a-helix formation by peptides in water - Stability and dynamics of peptide conformation - An overview of structure-function studies of peptide hormones - Neuropeptides:peptide and nonpeptide analogs - Reversible inhibitors of serine proteinases - Design of polypeptides - Current capabilities and future possibilities of soluble chemical combinatorial libraries - Epitope mapping with peptides - Synthesis and applications of branched peptides in immunological methods and vaccines
Both novices and experts will benefit from this insightful step-by-step discussion of phage display protocols.Phage Display of Peptides and Proteins: A Laboratory Manual reviews the literature and outlines the strategies for maximizing the successful application of phage display technology to one's research. It contains the most up-to-date protocols for preparing peptide affinity reagents, monclonal antibodies, and evolved proteins. - Prepared by experts in the field - Provides proven laboratory protocols, troubleshooting, and tips - Includes maps, sequences, and sample data - Contains extensive and up-to-date references
Focuses on Biology, Pharmacology, and Therapeutic Applications The study and diverse applications of bioactive peptides traverse many sub-disciplines within chemistry, biology, physics, and medicine. Answering a long-standing need, Bioactive Peptides focuses on the biology, pharmacology, and therapeutic applications of endogenous peptide mediators and their analogues. Moving peptide science beyond chemical synthesis strategies and into the realms of peptide biology and therapeutics, it presents the overall contribution that peptide science has made to molecular, cellular, and whole organism biology, while also discussing future targets and therapeutic applications. Beneficial for Experts and Novices Alike Part I provides details of bioactive peptides that interact with common drug targets and analyzes some of the most competitive areas of current research worldwide. While it is widely known that mammalian physiological systems utilize bioactive peptides that have yet to be discovered, other animals provide a rich and valuable source of bioactive peptides. This fascinating area of science is the theme of Part II. Parts III and IV investigate the unique bioactivities of various peptides that are ripe for further exploration. This definitive reference also includes: A detailed description and analysis of a broad range of peptides that interact with G protein-coupled receptors, the quantitatively dominant drug target A discussion of non-ribosomal peptides, which hold promise as sources of endogenous mediators Important examples of common methodologies employed to identify, characterize, and further develop bioactive peptides from a range of natural sources With mounting worldwide interest in their therapeutic potential, bioactive peptides--includ
With combinatorial chemistry millions of organic compounds can be produced simultaneously, quickly, and in most cases by automated procedures. These compound libraries are a cost-effective resource for the pharmaceutical industry in their search for biologically active lead structures. Furthermore simultaneous parallel synthesis of single peptides and peptide libraries solve the problem of the worldwide increasing demand for peptides. The synthetic methods described here in detail contribute to a forward-looking technology that has a high impact for industrial and academic research. Fast and efficient analytical techniques are essential for using the complicated product mixtures and detecting by-products. Various synthetic approaches and technologies, mass spectrometry, and screening assays are discussed extensively. This book is a must and an indispensible source of information for every researcher in this rapidly developing field, which spans organic synthesis, biochemistry, biotechnology, pharmaceutical, medicinal, and clinical chemistry.
Several books and many papers have been published during the last decade on the design and the use of new nanomaterials in medicine and technology, which describe major concepts of nanotechnology. Meanwhile, a new promising type of nanomaterials-bacteriophages-emerged recently as a result of the evolution of phage display technique. Bacteriophages have a unique feature - completely the opposite of other nanomaterials -their structure and function are encrypted in their genomic DNA, which can be intentionally modified or even rewritten using routine genetic engineering techniques. In particular, a paradigm of landscape phage with multivalently displayed foreign peptides evolved, which allows constructing phage with unique surface architectures and emerged properties. Recently, phage, as a new kind of nanomaterials attracted the attention of specialists working in peripheral, and even very diverse areas from genetics and molecular biology, such as pharmaceutical science, material science, microelectronics, biosensors, detection, environmental sciences, etc. Penetration of the phage technology into these new disciplines required the development of a new instructive concept, which resulted in this publication. This comprehensive book, of value to researchers as well as scientists, introduces readers into this hot new area of phage nanobiotechnology. It summarises the existing data on the phage nanomaterials and discusses their use in different areas of medicine, science and technology. With contributions by top level experts and pioneers in phage display, the major goal of this book is to bring the phage display technique closer to specialists in these diverse areas of medicine, science and technology, where phage-derived nanomaterials can be most beneficial.
Peptide Applications in Biomedicine, Biotechnology and Bioengineering summarizes the current knowledge on peptide applications in biomedicine, biotechnology and bioengineering. After a general introduction to peptides, the book addresses the many applications of peptides in biomedicine and medical technology. Next, the text focuses on peptide applications in biotechnology and bioengineering and reviews of peptide applications in nanotechnology. This book is a valuable resource for biomaterial scientists, polymer scientists, bioengineers, mechanical engineers, synthetic chemists, medical doctors and biologists. - Presents a self-contained work for the field of biomedical peptides - Summarizes the current knowledge on peptides in biomedicine, biotechnology and bioengineering - Covers current and potential applications of biomedical peptides
The continued successes of large- and small-scale genome sequencing projects are increasing the number of genomic targets available for drug d- covery at an exponential rate. In addition, a better understanding of molecular mechanisms—such as apoptosis, signal transduction, telomere control of ch- mosomes, cytoskeletal development, modulation of stress-related proteins, and cell surface display of antigens by the major histocompatibility complex m- ecules—has improved the probability of identifying the most promising genomic targets to counteract disease. As a result, developing and optimizing lead candidates for these targets and rapidly moving them into clinical trials is now a critical juncture in pharmaceutical research. Recent advances in com- natorial library synthesis, purification, and analysis techniques are not only increasing the numbers of compounds that can be tested against each specific genomic target, but are also speeding and improving the overall processes of lead discovery and optimization. There are two main approaches to combinatorial library production: p- allel chemical synthesis and split-and-mix chemical synthesis. These approaches can utilize solid- or solution-based synthetic methods, alone or in combination, although the majority of combinatorial library synthesis is still done on solid support. In a parallel synthesis, all the products are assembled separately in their own reaction vessels or microtiter plates. The array of rows and columns enables researchers to organize the building blocks to be c- bined, and provides an easy way to identify compounds in a particular well.
Peptide Nucleic Acids, Second Edition has been extensively revised, updated, and enlarged to contain many new chapters covering the most recent topics and applications in this fast-moving field. The book contains state-of-the-art protocols and applications on all aspects of peptide nucleic acids. Concepts are clearly explained with each chapter containing concise background information. Written by leading experts in the field, the book is an invaluable and complete reference work on this novel and exciting area.
Including case studies of macrocyclic marketed drugs and macrocycles in drug development, this book helps medicinal chemists deal with the synthetic and conceptual challenges of macrocycles in drug discovery efforts. Provides needed background to build a program in macrocycle drug discovery –design criteria, macrocycle profiles, applications, and limitations Features chapters contributed from leading international figures involved in macrocyclic drug discovery efforts Covers design criteria, typical profile of current macrocycles, applications, and limitations