Download or read book The Synthesis and Applications of Sulfoxide Ligands and Methodology Development Towards Beta Amino Acid Incorporation in Peptides written by Priscilla Leung and published by . This book was released on 2011 with total page 146 pages. Available in PDF, EPUB and Kindle. Book excerpt: The incorporation of beta-amino acid residues into polypeptides has resulted in new foldamers whose structures and enhanced stability provide interesting opportunities for new biological applications. A novel strategy for an iterative peptide synthesis involving beta-amino acids will be proposed. Lastly, a hydroamidation-type strategy for the construction of beta 3-amino acids, or more specifically of beta-(N-acylamino)acrylates, will be presented as preliminary work towards the goal of dipeptide synthesis.The use of sulfoxide ligands for transition metal catalyzed transformations has recently been brought to the forefront in organic chemistry. The synthesis of a series of tri- and disulfoxides will be presented, and their applications investigated. Their use in rhodium catalyzed 1,4-additions of phenylboronic acid to 2-cyclohexen-1-one result in enantioselectivities up to 80%.
Download or read book The DESIGN AND SYNTHESIS OF NOVEL UNNATURAL AMINO ACIDS AND THE DESIGN AND SYNTHESIS OF PEPTIDES PEPTIDOMIMETICS CONTAINING UNNATURAL AMINO ACIDS FOR THE STUDY OF G PROTEIN COUPLED RECEPTORS written by and published by . This book was released on 2010 with total page 454 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nature has gifted peptides as important modulators in the human body, but these types of molecules often have not been favored when we were looking for therapeutic agents. The poor bioavailability, fast degradation and until recent high manufacturing costs of some bioactive peptides lowered their potential usage in the health industry. Under these circumstances, unnatural amino acids were developed as indispensible tools providing enormous support to peptide science. By incorporating proper unnatural amino acids into a peptide or protein, we now can significantly improve peptide's or protein's half-life, cell permeability, bio-distribution, etc. In addition, their potency and receptor/acceptor selectivity could also be enhanced. Site-specific modifications of peptides and proteins under physiological conditions with the use of unnatural amino acids also have been made easier with the advance of biotechnology. Therefore, my research described in this dissertation contributes to the efforts in the development of novel unnatural amino acids. In particular, I have focused on novel methods in the synthesis of anti beta-functionalized gamma, delta-unsaturated amino acids. These amino acids have special interests in peptide chemistry: they can provide conformational constraints to the peptide 3D structures; the beta-functionalization allows the introduction of pharmaceutically interesting side chain groups; and the terminal double bond which is orthogonal to peptide synthesis provides access to further chemical modifications. Two general methodologies for the synthesis of both racemic and optically active anti beta-functionalized gamma, delta--unsaturated amino acids were developed by using the thio-Claisen rearrangement (TCR) reaction. Excellent diastereoselectivies and enantioselectivities were obtained when C2-symmetric chiral auxiliaries were selected to control the stereochemistry outcome. The mechanism and the scope of the TCR reaction were also studied, showing unique advantages in the preparation of these biological interesting amino acids. Another effort of developing angiotensin II type 1 (AT1) receptor biased peptide ligands is also documented in this dissertation. The AT1 receptor is a 7-transmembrane G-protein coupled receptor, which recent researches have shown could be activated through a beta-arrestins only, but G-protein independent, pathway. We synthesized 12 analogs of Sar1,Ile4,Ile8-AngII (SII), and tested them in biological assays, and obtained valuable information for further "perfect" biased ligands design.
Download or read book PART I DESIGN AND SYNTHESIS OF BICYCLIC INTERNAL BETA TURN MIMETICS AND THEIR INCORPORATION INTO BIOLOGICALLY ACTIVE LIGANDS PART II SYNTHESIS OF CYCLIC PEPTIDES BY RING written by and published by . This book was released on 2010 with total page 604 pages. Available in PDF, EPUB and Kindle. Book excerpt: Beta-Turns in many biologically active peptides are important secondary structural elements which are critical for their biological activities. Hence, it is not surprising that beta-turn based pharmacophore design including beta-turn mimetics has become a central topic in medicinal chemistry in addition to alpha-helix or helical peptides. One of the advantages of such beta-turn mimetics is that they can better control torsion angles of the backbone of peptides and to some degree dihedral angles chi (X). These beta-turn mimicking scaffolds are designed to have a higher avidity for the acceptor by overcoming what otherwise is the inherent entropic cost paid for beta-turn formation upon binding to the acceptor. Among different synthetic strategies to bicyclic structures as beta-turn mimetics, consecutive formation of bicyclic structures using tandem acid-catalyzed N-acyliminium ion cyclization is attractive since this methodology was well established in the synthesis of natural product alkaloids. 1,3,6,8-Substituted tetrahydro-2H-pyrazino[1,2-a]pyrimidine-4,7-diones were designed and synthesized as internal beta-turn mimetics through an acid-catalyzed tandem acyliminium ion cyclization. Its development and synthesis are decribed in Chapter 2 to Chapter 4. Its application toward the development and synthesis of a small molecule ligand for melanocortin receptors is described in Chapter 5. In addition, the development of peptidomimetics for opioid receptors is explained in Chapter 6. On the other hand, a dicarba analogue having opioid receptor agonist, and dicarba analogues for MCRs were synthesized through solid phase synthesis including a ring closing metathesis reaction using Grubbs' catalyst (I) in Chapter 8.
Download or read book Studies on Chemical Synthesis of Peptides written by Vasanthakumar Ganga Ramu and published by GRIN Verlag. This book was released on 2011-10-28 with total page 189 pages. Available in PDF, EPUB and Kindle. Book excerpt: Doctoral Thesis / Dissertation from the year 2004 in the subject Chemistry - Organic Chemistry, Bangalore University / Central College (Department of Studies in Chemistry), language: English, abstract: The importance of ß-amino acids has been focused, particularly in the past few decades. They are found as components of many biologically active peptidic and nonpeptidic natural products with antibiotic, antifungal, cytotoxic, and other pharmacological properties. ß-Amino acids are produced in humans, animals, microorganisms, marine organisms, and plants either in free state or as part of a peptide or depsipeptide. The importance of nonpeptidic ß-amino acids has been nfocused particularly on the ß-lactam antibiotics, since naturally occurring penicillin derivatives have been discovered as broad antibiotic active agents. Over the years, a large number of these compounds have been prepared and tested, and a variety of new ß-lactam ring systems have been introduced such as cephems, cephalosporins, oxacephems, penems, carbapenems, oxapenams as well as monocyclic and polycyclic ring systems. ß-Amino acids have been known to play an important role in primary and secondary metabolism also. [...]
Download or read book Synthesis of Novel Amino Acids and Use of Peptides Peptidomimetics Containing Unnatural Amino Acids for the Development of Selective Melanocortin Peptide Antagonists and for the Study of Melanocortin Receptor Signaling written by Hongchang Qu and published by . This book was released on 2007 with total page 366 pages. Available in PDF, EPUB and Kindle. Book excerpt: Unnatural amino acids are indispensible tools, not only for the elucidation of molecular mechanisms during the study of the complicated biological system, but also for the development of novel peptide and protein drugs with better efficacy and lower toxicity. Beta-substituted gamma, delta-unsaturated amino acids have been shown to be an important type of novel amino acid because of the terminal double bond which can be converted to many other functionalities. The methodology for the synthesis of syn-beta-substituted gamma, delta-unsaturated amino acids has been developed. However, there is no satisfactory general method for the synthesis of anti-beta-substituted gamma, delta-unsaturated amino acids. Therefore, a general methodology was developed by using the Eschenmoser-Claisen rearrangement for the synthesis of both racemic and optically active anti-beta-substituted gamma, delta-unsaturated amino acids. This rearrangement is highly diastereoselective and good asymmetric induction was obtained with a relatively small C2-symmetric chiral auxiliary (2R,5R)-dimethylpyrrolidine. In an effort to design peptide antagonists that are selective for human melanocortin 4 receptor, highly constrained trans and cis 4-guanidinium proline derivatives were synthesized and incorporated in various melanotropin analogues designed to mimic the endogenous hMC1,4R selective antagonist hASIP (Agouti Signaling Protein) central loop. Biologicalassays show that some of these analogues are highly selective for hMC1R and/or hMC4R with partial agonist or antagonist activities due to a new beta-turn structure induced by the presence of the constrained amino acids. According to molecular modeling studies, the lowest energy conformations of these selective analogues resemble the NMR solution structure of the hASIP central loop. Therefore, a new template was developed for the rational design of novel selective melanotropin analogues that may have therapeutic potential. To further understand the molecular mechanisms of hMC4R signaling upon agonist activation, an hMC4R selective nonpeptide agonist THIQ and its fluorescent dye labeled derivatives were needed to compare to peptide agonist MTII with regard to receptor phosphorylation, internalization, etc. An improved synthetic method was developed for the efficient synthesis of THIQ. A method for the synthesis of TRITC labeled THIQ derivatives was also developed.
Download or read book Chemical Ligation written by Luca D. D'Andrea and published by John Wiley & Sons. This book was released on 2017-03-16 with total page 584 pages. Available in PDF, EPUB and Kindle. Book excerpt: Presenting a wide array of information on chemical ligation – one of the more powerful tools for protein and peptide synthesis – this book helps readers understand key methodologies and applications that protein therapeutic synthesis, drug discovery, and molecular imaging. • Moves from fundamental to applied aspects, so that novice readers can follow the entire book and apply these reactions in the lab • Presents a wide array of information on chemical ligation reactions, otherwise scattered across the literature, into one source • Features comprehensive and multidisciplinary coverage that goes from basics to advanced topics • Helps researchers choose the right chemical ligation technique for their needs
Download or read book Synthesis of Optically Active alpha amino Acids written by Robert Michael Williams and published by Pergamon. This book was released on 1989 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: The purpose of this book is to review and critically evaluate the best new methods to synthesize alpha-amino acids in optically active form. There is so much new literature on amino acid synthesis that the experimentalist will undoubtedly have difficulty in selecting the most appropriate methodology for constructing the amino acid of immediate interest. This book is a guide for steering the scientist through the maze of existing reports on the subject and contains the most up-to-date critical reviews of methods of asymmetric synthesis of amino acids. In areas that are relatively new conceptually and less studied experimentally, an effort has been made to review the most salient works with an eye towards future development. Over 330 schemes and figures are presented with references for rapid visual retrieval of information. The book will be of great value to academic and industrial organic research chemists, especially those concerned with medicinal and agricultural chemistry, as well as to graduate and post graduate students, biochemists and biologists.
Download or read book Synthesis of Conformationally Restricted beta turn Mimics written by Maarten IJsselstijn and published by . This book was released on 2006 with total page 157 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book I Methodology Development for the Synthesis of Geminally Disubstituted beta amino Acids beta proline Analogs and Allylic Amines II Progress Towards the Synthesis of an Artificial Transcription Activator written by Bin Chen and published by . This book was released on 2005 with total page 380 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Development of alpha helix like alpha beta upsilon Foldamers written by and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Helical peptidomimetics that contain non-natural amino acid residues, such as beta- and gamma-amino acid residues, are less prone to proteolytic degradation than are conventional peptides (composed exclusively of alpha-amino acid residues). However, the additional backbone atoms in beta- and gamma-residues relative to alpha-residues may increase backbone flexibility, and thereby increase the entropic penalty upon binding to a protein partner, resulting in decreased affinity for the targets. Ring-constrained beta- and gamma-amino acids have been developed to address this problem by pre-organizing the residues for helical conformations. This thesis details development of alpha-helix-like alpha/beta/gamma foldamers containing cyclic and/or acyclic beta- and gamma-amino acid residues. Chapters 2 and 3 discuss biophysical investigations of helical alpha/beta/gamma-peptides. Studies of the ring-constrained beta- and gamma-residues' effects on the helicity of alpha/beta/gamma-peptides suggest that beta(3)- and gamma(4)- amino acid residues differ in their intrinsic tendencies to adopt helical secondary structure, with gamma(4)-residues displaying a higher propensity than beta(3)- residues. Different acyclic gamma-residues, and different patterns of alpha, beta and gamma residues in the backbone have been explored. The results show that as long as cyclically constrained beta-amino acids are incorporated into alpha/beta/gamma-peptides, the alpha/beta/gamma-peptide helical propensity is not very sensitive to the nature of the acyclic gamma-amino acids used (although gamma(4)-amino acids are the best helix-adopting acyclic residues) or the pattern of residues within the backbone. Chapter 4 discusses efforts to establish an alpha + alpha/beta/gamma coiled-coil system for use in thermodynamic analysis of alpha + alpha/beta/gamma coiled-coil folding propensities. Chapter 5 discusses efforts toward developing functional alpha/beta/gamma-peptides to modulate apoptosis-regulating protein-protein interactions.
Download or read book Chemistry of Peptide Synthesis written by N. Leo Benoiton and published by CRC Press. This book was released on 2016-04-19 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chemistry of Peptide Synthesis is a complete overview of how peptides are synthesized and what techniques are likely to generate the most desirable reactions. Incorporating elements from the author's role of Career Investigator of the Medical Research Council of Canada and his extensive teaching career, the book emphasizes learning rather th
Download or read book Solid Phase Peptide Synthesis written by Gregg B. Fields and published by Academic Press. This book was released on 1997-10-21 with total page 828 pages. Available in PDF, EPUB and Kindle. Book excerpt: The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volumehas been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. More than 275 volumes have been published (all of them still in print) and much of the material is relevant even today-truly an essential publication for researchers in all fields of life sciences. Key Features * Solid-phase peptide synthesis * Applications of peptides for structural and biological studies * Characterization of synthetic peptides
Download or read book New Methods Towards the Synthesis of beta amino Acids written by Barbara Weiner and published by . This book was released on 2009 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Chemical Approaches to the Synthesis of Peptides and Proteins written by Paul Lloyd-Williams and published by CRC Press. This book was released on 1997-04-23 with total page 306 pages. Available in PDF, EPUB and Kindle. Book excerpt: Organic chemists working on the synthesis of natural products have long found a special challenge in the preparation of peptides and proteins. However, more reliable, more efficient synthetic preparation methods have been developed in recent years. This reference evaluates the most important synthesis methods available today, and also considers methods that show promise for future applications. This text describes the state of the art in efficient synthetic methods for the synthesis of both natural and artificial large peptide and protein molecules. Subjects include an introduction to basic topics, linear solid-phase synthesis of peptides, peptide synthesis in solution, convergent solid-phase synthesis, methods for the synthesis of branched peptides, formation of disulfide bridges, and more. The book emphasizes strategies and tactics that must be considered for the successful synthesis of peptides.
Download or read book Concise Encyclopedia of Biomedical Polymers and Polymeric Biomaterials written by Munmaya Mishra and published by CRC Press. This book was released on 2017-08-16 with total page 1800 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Concise Encyclopedia of Biomedical Polymers and Polymeric Biomaterials presents new and selected content from the 11-volume Biomedical Polymers and Polymeric Biomaterials Encyclopedia. The carefully culled content includes groundbreaking work from the earlier published work as well as exclusive online material added since its publication in print. A diverse and global team of renowned scientists provide cutting edge information concerning polymers and polymeric biomaterials. Acknowledging the evolving nature of the field, the encyclopedia also features newly added content in areas such as tissue engineering, tissue repair and reconstruction, and biomimetic materials.
Download or read book The Synthesis of Bicyclic Guanidino Amino Acids written by Steven Hill and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Small molecules, such as oligopeptides can interact with nucleic acid targets and subsequently stimulate or supress biological functions. The purpose of this thesis was to produce nucleic acid targeting oligopeptides which contain non-natural amino acids as part of their sequence. Certain amino acids display selectivity for certain nucleobases. Arginine has a high propensity for being present at the binding interface of both protein-DNA and protein-RNA complexes. This thesis was aimed at the synthesis of two arginine analogues in which the guanidino side chain was locked in a bicyclic framework. It was expected that this would result in highly directional H-bonding capabilities of the side chains of the two analogues, which was predicted to give superior selectivity when discriminating between targets. This thesis discusses the synthetic routes undertaken in an attempt to produce these two analogues. The synthesis of the two analogues proceeded by quite different routes. The first entailed manipulation of a chiral starting material to ultimately produce the bicyclic guanidine. However, incorporation of the amino acid moiety proved difficult and thus is incomplete. However, there is scope for further work to build on the endeavours mentioned in this work. The attempted synthesis of the second analogue focused on the formation of a substituted triamine prior to cyclisation to give the bicyclic guanidine. This method also produced many problems and so the synthesis still requires further work. The thesis also details the design and synthesis of a peptide library with the majority of peptides possessing at least one arginine residue within their sequence. This produced a range of peptides in small quantities (nanomolar) which was screened against an enzyme-linked immunosorbent assay (ELISA). The results of the assay highlighted library members who displayed a binding affinity towards the oligonucleotide targets and from this their sequences were determined. Future work can be performed using these results so that binding association constants can be determined. Once the arginine analogues have been successfully synthesised these can be incorporated into these peptide sequences in place of the arginine residues.
Download or read book Two Dimensional Electrophoresis Protocols written by David Sheehan and published by Humana Press. This book was released on 2009-04-01 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The human genome and other large-scale genome sequencing projects have inevitably led to a focus on the proteins encoded by genes. The field of proteomics has grown enormously as a result and a number of high-throughput technologies have now been developed allowing discovery-led investigations of protein populations rather than more traditional hypothesis-led studies on single proteins. These high-throughput techno- gies include gene and protein microarrays, the yeast two-hybrid system, and various mass spectrometry methodologies. However, despite developments and improvements in these technologies, two-dimensional electrophoresis (2DE) remains one of the most widely used approaches. This technique was revolutionised by the development of immobilised pH gradient strips which are now commercially available. This has made possible highly reproducible separations of matched samples. Developments in staining, mass spectr- etry, and bioinformatics supported these developments and have led to a measure of standardisation in design, execution, and analysis of proteomics experiments. This book began life as a proposed update of the excellent volume 2DE Protocols edited by Andrew Link of the University of Washington at Seattle. However, we re- ised that 2DE has undergone major development in aspects of its technology in recent years and we were anxious to reflect these in the present volume. We are also conscious that many researchers have now begun to apply proteomics methodologies to a growing range of biological material and we were anxious to include contributions to reflect the challenges posed in sample preparation in less widely used organisms.
