Download or read book Combinatorial Peptide and Nonpeptide Libraries written by Günther Jung and published by John Wiley & Sons. This book was released on 2008-09-26 with total page 571 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Combinatorial Peptide Library Protocols written by Shmuel Cabilly and published by Springer Science & Business Media. This book was released on 2008-02-02 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Synthetic Combinatorial Peptide Libraries and Their Application in Decoding Biological Interactions written by Michael Cameron Sweeney and published by . This book was released on 2005 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: The synthesis of peptides was revolutionized by the adoption of solid-phase synthetic techniques. Subsequent improvement, evolution, and refinement of this chemical technique has allowed research into areas of biology not previously accessible with such speed and breadth. Because of the efficiency and flexibility of the chemistry involved in peptide synthesis, libraries representing millions of unique natural, modified, or unnatural peptides can be constructed rapidly and in high enough purity as to obviate the need for purification. In this work, libraries were synthesized for screening against individual protein domains in an effort to both determine the preferred peptidyl binding partner types for each, as well as to establish an optimized, broadly applicable methodology for screening other domains. One of the problems encountered during the development of the screening methodology was the low success-rate of sequence determination for the peptides selected by each domain. Herein we report the successful modification of the peptide ladder mass spectrometry sequencing technique referred to as partial Edman degradation (PED). Success-rates were improved to greater than 90% for full-length sequencing determination of peptide up to 8-mers, even for more difficult phosphotyrosine (pY)-containing peptides. As a result of this improvement, three pY-binding Src Homology 2 (SH2) domains and two N-terminus binding Baculoviral Inhibitor-of-Apoptosis Repeat (BIR) domains were screened against their respective libraries and the preferred ligand types for each was determined. The advantage of sequencing by the PED method became especially clear in the case of the N-terminal SH2 (N-SH2) domain of Src Homology 2 Protien Tyrosine Phosphatase 2 (SHP-2) as previously unidentified sub-classes of binding consensus motifs were distinguishable due to the discreet nature of the sequencing technique. This work demonstrates the usefulness and potential generality of peptide library screening by this method.
Download or read book Combinatorial Chemistry written by Stephen R. Wilson and published by John Wiley & Sons. This book was released on 1997-03-28 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt: The new time-saving revolution in drug discovery. Combinatorial chemistry, a method for synthesizing millions of chemical compounds much faster than usual, is becoming one of the most useful technical tools available to chemists and researchers working today. Using current advances in computer and laboratory techniques, combinatorial chemistry has freed professionals from the drudgery of piecemeal experimental work and opened new creative possibilities for experimentation. Combinatorial Chemistry: Synthesis and Application details critical aspects of the technique, featuring the work of some of the world's leading chemists, many of whom played a key role in its development. Including examples of both solution-phase and solid-phase approaches as well as the full complement of organic chemistry technologies currently available, the book describes: * Concepts and terms of combinatorial chemistry * Polymer-supported synthesis of organic compounds * Macro beads as microreactors * Solid-phase methods in combinatorial chemistry * Encoded combinatorial libraries, including Rf-encoding of synthesis beads * Strategies for combinatorial libraries of oligosaccharides * Combinatorial libraries of peptides, proteins, and antibodies using biological systems. While combinatorial chemistry originated in peptide chemistry, this volume has deliberately focused on nonpeptide organic applications, illustrating the technique's wide uses. Combinatorial Chemistry introduces organic, medicinal, and pharmaceutical chemists as well as biochemists to this exciting, cost-effective, and practical technique, which has unlocked creative potential for the next millennium.
Download or read book Solid Phase Synthesis of Combinatorial Peptide Libraries written by Steven O. Mansoorabadi and published by . This book was released on 2000 with total page 70 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Combinatorial Libraries written by Riccardo Cortese and published by Walter de Gruyter. This book was released on 2013-08-26 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Combinatorial Chemistry written by Nicholas K. Terrett and published by . This book was released on 1998 with total page 204 pages. Available in PDF, EPUB and Kindle. Book excerpt: Combinatorial chemistry, by accelerating the process of chemical synthesis, is having a profound effect on all branches of chemistry, but especially on drug discovery. This informative text explains the origins of combinatorial chemistry and puts the many diverse library methods into context.It explains why some techniques are generally applicable and others are for specialists only. It also focuses on the renaissance of solid phase chemistry and describes the range of available reactions. This is the first single author book in this important, growing field and it describes thebeneficial impact of combinatorial chemistry, especially for the discovery and optimisation of biologically active molecules. This concise and comprehensive overview of combinatorial techniques is an essential text for final year undergraduates, postgraduates, academics and industrialists inchemistry, bio-orgainc chemistry, medicinal chemistry and drug discovery. It provides an accessible introduction to the area for those new to these methods and a valuable reference text to those experienced in this field.
Download or read book Combinatorial Library written by Lisa B. English and published by Springer Science & Business Media. This book was released on 2008-02-04 with total page 380 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Design of Peptide and Non peptide Libraries written by Rikke Malene Jørgensen and published by . This book was released on 2001 with total page 174 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Bioactive Peptides written by John Howl and published by CRC Press. This book was released on 2019-08-30 with total page 503 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book Encyclopedia of Molecular Biology and Molecular Medicine Plasmids to Synthetic Peptide and Nonpeptide Combinatorial Libraries written by Robert A. Meyers and published by Wiley-Blackwell. This book was released on 1996-12-12 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This six volume Encyclopedia is the most comprehensive, detailed treatment of molecular biology and molecular medicine available today! The Encyclopedia provides a single-source library of molecular genetics and the molecular basis of life, with a focus on molecular medicine. Genetic screening, gene therapy, structural biology, and the technology and findings of the Human Genome Project are discussed in detail. The articles that comprise the set are designed as self-contained treatments. Each of the nearly 300 articles begins with an outline and a key word section which includes definitions. These features assist the scientist or student who is unfamiliar with a specific subject area. A glossary of basic terms completes each volume and defines the most commonly used terms in molecular biology. Together with the introductory illustrations found in each volume, these definitions enable readers to understand articles without referring to a dictionary, textbook, or other reference.
Download or read book Peptides written by Bernd Gutte and published by Elsevier. This book was released on 1995-10-24 with total page 527 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book Synthesis and Screening of a Combinatorial Peptide Library for Ligands to Target Transferrin written by Jennifer Marie Brown and published by . This book was released on 2010 with total page 64 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Zur fr hen Geschichte written by and published by . This book was released on 1970 with total page 1186 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Screening Combinatorial Peptide Libraries in Complex Mixtures for Applications in Therapeutic Delivery and Molecular Diagnostics written by Sejal Sampat Hall and published by ProQuest. This book was released on 2008 with total page 276 pages. Available in PDF, EPUB and Kindle. Book excerpt: An auto-fluorescent bacterial display peptide library was used to isolate red blood cell (RBC) binding ligands which were used to attach nanoparticles to the RBC surface to develop novel long circulating drug delivery vehicles. Bacterial display was also employed to isolate tissue targeting ligands in vivo. Finally, multi-color FACS was used to quantitatively isolate highly-specific peptides and further optimize their specificity for a target antibody present at a 10,000 - 100,000 fold dilution in serum IgG. The method was employed to screen serum antibodies of patients with Celiac Disease to identify potential biomarker candidates. The method developed here enables quantitative screening and evolution of specificity, enhancing the current repertoire of screening methods available in protein engineering.
Download or read book Screening Combinatorial Peptide Library for Optimal Enzyme Substrates and High Affinity Protein Ligands written by Peng Wang and published by . This book was released on 2003 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: A method for the rapid identification of high-affinity ligands was used to study the specificity of the interaction between FHA2 domain of Rad53 and phosphotyrosyl peptide. A phosphotyrosyl (pY) peptide library containing completely randomized residues at positions -2 to +3 relative to the pY was synthesized on TentaGel resin, with a unique peptide sequence on each resin bead. The library was screened against the biotinylated FHA2 domains, and the beads that carry high-affinity ligands of the FHA2 domains were identified using an enzyme-linked assay. Peptide ladder sequencing of the hundreds of selected beads using MALDI-TOF revealed consensus sequences for FHA2 domains. A new method was developed to rapidly sequence support-bound peptides derived from combinatorial peptide library. Support-bound peptides isolated from one-bead-one-compound libraries are subjected to partial Edman degradation in the presence of an N-terminal blocking agent (5% phenyl isocyanate). Repetition of the degradation reaction results in a series of sequence-specific truncation products (a peptide ladder). The sequence of the full-length peptide is determined by MALDI-TOF analysis of the peptide ladder. During screening of combinatorial libraries for optimal enzyme substrates, the challenge is to differentiate a reaction product(s) from a complex mixture of substrates. We have overcome this problem by partially labeling the substrates with a heavier isotope (heavy/normal isotope = 1:1), so that each member of the substrate library appears as a doublet in ESI-MS spectrum whereas the products appear as singlets in the spectrum, allowing for their unambiguous identification. The strategy has been successfully demonstrated by peptide deformylase screening. This method was further perfected in the screening of the pY library against the catalytic domain of SHP-1. Limited treatment of the library with a PTP removed phosphoryl group from the most preferred substrates to generate products as singlet peaks, which were readily identified in ESI-FTICR-MS spectrum and sequenced by tandem mass spectrometry. Several selected peptides were individually synthesized and assayed against SHP-1 and the kinetic data confirmed the screening results.
Download or read book Synthesis and Screening of Support bound Combinatorial Cyclic Peptide and Free C terminal Peptide Libraries written by Sang Hoon Joo and published by . This book was released on 2007 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: One-bead one-compound (OBOC) peptide libraries have been useful tools in the biomedical sciences. However, OBOC peptide libraries usually display the N-termini of peptides on the surface as conventional solid phase peptide synthesis proceeds in the C to N direction. While large combinatorial libraries of cyclic peptides can be synthesized by the split-and-pool synthesis method, the sequence determination has been a challenge. Also, peptide libraries with free C-termini face the same problem as well as the difficulty of synthesis in the N to C direction. We report here the development of cyclic peptide libraries and C-terminal peptide libraries for high-throughput screening and sequencing. TentaGel microbeads (90 um) were spatially segregated into outer and inner layers; cyclic peptides were displayed on the bead surface, whereas the inner core of each bead contained the corresponding linear encoding peptide. After screening of the cyclic peptide library, the identity of hit peptides was determined by sequencing the linear encoding peptides using a partial Edman degradation/mass spectrometry method. Using the same spatial segregation approach peptides were synthesized in the conventional C to N direction, with their C-termini attached to the support through an ester linkage on the bead surface but through an amide bond in the inner layer. The surface peptides were cyclized between N-terminal amine and a carboxyl group installed at a C-terminal linker sequence, while the internal peptides stayed in the linear form. Base hydrolysis of the ester linkage in the cyclic peptides exposed a free [alpha]-carboxyl group at the C-termini of the peptides attached to the resin via the N-termini. An inverted peptide library containing five random residues was synthesized and screened for binding to PDZ domains. The identity of the binding peptides was determined from the encoding peptides. Consensus recognition motifs were identified for the PDZ domains and representative peptides were individually synthesized and confirmed for binding to their cognate PDZ domains. These methods expanded the utility of OBOC peptide libraries by displaying peptides in different ways.
