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Combinatorial Peptide Library Protocols

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Release : 2008-02-02
Genre : Science
Kind : eBook
Book Rating : 715/5 ( reviews)

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Book Synopsis Combinatorial Peptide Library Protocols by : Shmuel Cabilly

Download or read book Combinatorial Peptide Library Protocols written by Shmuel Cabilly. This book was released on 2008-02-02. 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.

Combinatorial Library

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Author :
Release : 2008-02-04
Genre : Science
Kind : eBook
Book Rating : 856/5 ( reviews)

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Book Synopsis Combinatorial Library by : Lisa B. English

Download or read book Combinatorial Library written by Lisa B. English. This book was released on 2008-02-04. 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.

Combinatorial Peptide and Nonpeptide Libraries

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Author :
Release : 2008-09-26
Genre : Science
Kind : eBook
Book Rating : 907/5 ( reviews)

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Book Synopsis Combinatorial Peptide and Nonpeptide Libraries by : Günther Jung

Download or read book Combinatorial Peptide and Nonpeptide Libraries written by Günther Jung. This book was released on 2008-09-26. 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.

Solid Phase Synthesis of Combinatorial Peptide Libraries

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Author :
Release : 2000
Genre : Combinatorial chemistry
Kind : eBook
Book Rating : /5 ( reviews)

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Book Synopsis Solid Phase Synthesis of Combinatorial Peptide Libraries by : Steven O. Mansoorabadi

Download or read book Solid Phase Synthesis of Combinatorial Peptide Libraries written by Steven O. Mansoorabadi. This book was released on 2000. Available in PDF, EPUB and Kindle. Book excerpt:

Synthetic Combinatorial Peptide Libraries and Their Application in Decoding Biological Interactions

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Author :
Release : 2005
Genre : Amino acid sequence
Kind : eBook
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Book Synopsis Synthetic Combinatorial Peptide Libraries and Their Application in Decoding Biological Interactions by : Michael Cameron Sweeney

Download or read book Synthetic Combinatorial Peptide Libraries and Their Application in Decoding Biological Interactions written by Michael Cameron Sweeney. This book was released on 2005. 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.

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