Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 223
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Book Description
The field of peptidomimetics has rapidly grown into an area of great interest for the design and synthesis of pharmaceutical drug targets. The large array of natural peptides with biological function as well as the growing understanding of the roles of these peptides in biological events has led to a large interest in these compounds as drug candidates. The majority of peptide and peptide-like molecules have not found widespread pharmaceutical utility; however, due to there lability in biological systems. This major drawback leads to the necessity for the development of peptide-like molecules with increased stability under biological conditions. To this end there has been an increased interest in the development of unnatural amino acids for the synthetic modification of peptides and proteins. Presented in this dissertation is the synthesis of a series of unnatural amino acids designed for applications to [3+2] click cycloaddition reactions. It also covers the introduction of these amino acids into the sequence of peptides for the purpose of labeling the peptide with aryl triazole chromophores in an attempt to analyze the electron transfer capabilities of aryl triazoles. The information from the fluorescent studies of these peptides will provide a basis for the design of fluorophoric peptide probes that can be introduced into a peptide at any time under labile conditions. This methodology provides a powerful tool for the analysis of peptide structure and the analysis of peptide-macromolecular interactions.
Author:
Publisher: GRIN Verlag
ISBN: 3668663467
Category : Science
Languages : en
Pages : 53
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Book Description
Seminar paper from the year 2014 in the subject Chemistry - Bio-chemistry, grade: 1,0, LMU Munich (Chemie), language: English, abstract: In the present work a modified version of yellow fluorescent protein containing an unnatural structural homologue of the natural amino acid pyrrolysine with a norbornene moiety was produced by expression in Escherichia coli. The incorporation of the unnatural amino acid was achieved by amber stop codon suppression method. A bio-othogonal click reaction was performed, binding a synthetic fluorescent dye to the modified protein. All steps towards necessary for obtaining the genetically modified organism were performed and documented. The artificial amino acid, as well as the dye used in the click reaction were synthetically prepared. The success of the project was demonstrated by LC/MS studies of the products. Fluorescence spectroscopy of click reaction product and the protein was performed, but no conclusive proof of FRET effects could as yet be made. This point remains of interest for future studies.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 454
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Book Description
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.
Author: Hongchang Qu
Publisher:
ISBN:
Category :
Languages : en
Pages : 366
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Book Description
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.
Author: Paul R. Ortiz de Montellano
Publisher: Springer Science & Business Media
ISBN: 0387274472
Category : Medical
Languages : en
Pages : 702
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Book Description
Cytochrome P450: Structure, Mechanism, and Biochemistry, third edition is a revision of a review that summarizes the current state of research in the field of drug metabolism. The emphasis is on structure, mechanism, biochemistry, and regulation. Coverage is interdisciplinary, ranging from bioinorganic chemistry of cytochrome P450 to its relevance in human medicine. Each chapter provides an in-depth review of a given topic, but concentrates on advances of the last 10 years.
Author: Eric N. Jacobsen
Publisher: Springer Science & Business Media
ISBN: 9783540003335
Category : Science
Languages : en
Pages : 258
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Book Description
The first supplement to the three volume reference work "Comprehensive Asymmetric Catalysis" critically reviews new developments to the hottest topics in the field written by recognised experts. Eleven chapters which are already in the major reference work have been supplemented and additionally five new chapters have been included. Thus the state-of-the art in this area is now re-established. Together with the basic three volume book set this supplement is not only the principal reference source for synthetic organic chemists, but also for all scientific researchers who use chiral compounds in their work (for example, in biochemical investigations and molecular medicine) as well as for pharmaceutical chemists and other industrial researchers who prepare chiral compounds.
Author: Jianbo Wang
Publisher: John Wiley & Sons
ISBN: 3527829156
Category : Science
Languages : en
Pages : 450
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Book Description
Presents an up-to-date overview of the rapidly growing field of carbene transformations Carbene transformations have had an enormous impact on catalysis and organometallic chemistry. With the growth of transition metal-catalyzed carbene transformations in recent decades, carbene transformations are today an important compound class in organic synthesis as well as in the pharmaceutical and agrochemical industries. Edited by leading experts in the field, Transition Metal-Catalyzed Carbene Transformations is a thorough summary of the most recent advances in the rapidly expanding research area. This authoritative volume covers different reaction types such as ring forming reactions and rearrangement reactions, details their conditions and properties, and provides readers with accurate information on a wide range of carbene reactions. Twelve in-depth chapters address topics including carbene C-H bond insertion in alkane functionalization, the application of engineered enzymes in asymmetric carbene transfer, progress in transition-metal-catalyzed cross-coupling using carbene precursors, and more. Throughout the text, the authors highlight novel catalytic systems, transformations, and applications of transition-metal-catalyzed carbene transfer. Highlights the dynamic nature of the field of transition-metal-catalyzed carbene transformations Summarizes the catalytic radical approach for selective carbene cyclopropanation, high enantioselectivity in X-H insertions, and bio-inspired carbene transformations Introduces chiral N,N'-dioxide and chiral guanidine-based catalysts and different transformations with gold catalysis Discusses approaches in cycloaddition reactions with metal carbenes and polymerization with carbene transformations Outlines multicomponent reactions through gem-difunctionalization and transition-metal-catalyzed cross-coupling using carbene precursors Transition Metal-Catalyzed Carbene Transformations is essential reading for all chemists involved in organometallics, including organic and inorganic chemists, catalytic chemists, and chemists working in industry.
Author: Philippe Kalck
Publisher: Springer
ISBN: 3319341847
Category : Science
Languages : en
Pages : 287
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Book Description
The series Topics in Organometallic Chemistry presents critical overviews of research results in organometallic chemistry. As our understanding of organometallic structure, properties and mechanisms increases, new ways are opened for the design of organometallic compounds and reactions tailored to the needs of such diverse areas as organic synthesis, medical research, biology and materials science. Thus the scope of coverage includes a broad range of topics of pure and applied organometallic chemistry, where new breakthroughs are being achieved that are of significance to a larger scientific audience. The individual volumes of Topics in Organometallic Chemistry are thematic. Review articles are generally invited by the volume editors. All chapters from Topics in Organometallic Chemistry are published OnlineFirst with an individual DOI. In references, Topics in Organometallic Chemistry is abbreviated as Top Organomet Chem and cited as a journal
Author: Karl M. Kadish
Publisher: World Scientific
ISBN:
Category : Medical
Languages : en
Pages : 368
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Book Description
This is the first set of Handbook of Porphyrin Science.Porphyrins, phthalocyanines and their numerous analogues and derivatives are materials of tremendous importance in chemistry, materials science, physics, biology and medicine. They are the red color in blood (heme) and the green in leaves (chlorophyll); they are also excellent ligands that can coordinate with almost every metal in the Periodic Table. Grounded in natural systems, porphyrins are incredibly versatile and can be modified in many ways; each new modification yields derivatives demonstrated new chemistry, physics and biology, with a vast array of medicinal and technical applications.As porphyrins are currently employed as platforms for study of theoretical principles and applications in a wide variety of fields, the Handbook of Porphyrin Science represents a timely ongoing series dealing in detail with the synthesis, chemistry, physicochemical and medical properties and applications of polypyrrole macrocycles. Professors Karl Kadish, Kevin Smith and Roger Guilard are internationally recognized experts in the research field of porphyrins, each having his own separate area of expertise in the field. Between them, they have published over 1500 peer-reviewed papers and edited more than three dozen books on diverse topics of porphyrins and phthalocyanines. In assembling the new volumes of this unique Handbook, they have selected and attracted the very best scientists in each sub-discipline as contributing authors of the chaptersThis Handbook will prove to be a modern authoritative treatise on the subject as it is a collection of up-to-date works by world-renowned experts in the field. Complete with hundreds of figures, tables and structural formulas, and thousands of literature citations, all researchers and graduate students in this field will find the Handbook of Porphyrin Science an essential, major reference source for many years to come.
Author: Robert A. Moss
Publisher: John Wiley & Sons
ISBN: 1118730267
Category : Science
Languages : en
Pages : 506
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Book Description
Presents the most innovative results in carbene chemistry, setting the foundation for new discoveries and applications The discovery of stable carbenes has reinvigorated carbene chemistry research, with investigators seeking to develop carbenes into new useful catalysts and ligands. Presenting the most innovative and promising areas of carbene research over the past decade, this book explores newly discovered structural, catalytic, and organometallic aspects of carbene chemistry, with an emphasis on new and emerging synthetic applications. Contemporary Carbene Chemistry features contributions from an international team of pioneering carbene chemistry researchers. Collectively, these authors have highlighted the most interesting and promising areas of investigation in the field. The book is divided into two parts: Part 1, Properties and Reactions of Carbenes, explores new findings on carbene stability, acid-base behavior, and catalysis. Carbenic structure and reactivity are examined in chapters dedicated to stable carbenes, carbodicarbenes, carbenes as guests in supramolecular hosts, tunneling in carbene and oxacarbene reactions, and ultrafast kinetics of carbenes and their excited state precursors. Theoretical concerns are addressed in chapters on computational methods and dynamics applied to carbene reactions. Part 2, Metal Carbenes, is dedicated to the synthetic dimensions of carbenes, particularly the reactions and catalytic properties of metal carbenes. The authors discuss lithium, rhodium, ruthenium, chromium, molybdenum, tungsten, cobalt, and gold. All the chapters conclude with a summary of the current situation, new challenges on the horizon, and promising new research directions. A list of key reviews and suggestions for further reading also accompanies every chapter. Each volume of the Wiley Series on Reactive Intermediates in Chemistry and Biology focuses on a specific reactive intermediate, offering a broad range of perspectives from leading experts that sets the stage for new applications and further discoveries.
