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While adenosine triphosphate (ATP) is described as the universal currency of energy in all living organisms at the cellular level, the actual power lies in its phosphate tail. This book is the first dedicated to the field of nucleoside triphosphate (NTP). Its 13 chapters encompass the contributions of twenty scientists from both academia and industry. It provides collective information on the chemical, physiochemical, and biological properties of both natural and modified NTP and their application in life sciences. Three chapters review families of enzymes that depend on nucleotides for assembling DNA and RNA molecules. The appendix includes supporting NMR data.
Compiles current tested and proven approaches to synthesize novel nucleoside analogues Featuring contributions from leading synthetic chemists from around the world, this book brings together and describes tested and proven approaches for the chemical synthesis of common families of nucleoside analogues. Readers will learn to create new nucleoside analogues with desired therapeutic properties by using a variety of methods to chemically modify natural nucleosides, including: Changes to the heterocyclic base Modification of substituents at the sugar ring Replacement of the furanose ring by a different carbo- or heterocyclic ring Introduction of conformational restrictions Synthesis of enantiomers Preparation of hydrolitically stable C-nucleosides Chemical Synthesis of Nucleoside Analogues covers all the major classes of nucleosides, including pronucleotides, C-nucleosides, carbanucleosides, and PNA monomers which have shown great promise as starting points for the synthesis of nucleoside analogues. The book also includes experimental procedures for key reactions related to the synthesis of nucleoside analogues, providing a valuable tool for the preparation of a number of different compounds. Throughout the book, chemical schemes and figures help readers better understand the chemical structures of nucleoside analogues and the methods used to synthesize them. Extensive references serve as a gateway to the growing body of original research studies and reviews in the field. Synthetically modified nucleosides have proven their value as therapeutic drugs, in particular as antiviral and antitumor agents. However, many of these nucleoside analogues have undesirable side effects. With Chemical Synthesis of Nucleoside Analogues as their guide, researchers have a new tool for synthesizing a new generation of nucleoside analogues that can be used as therapeutic drugs with fewer unwanted side effects.
A review of innovative tools for creative nucleic acid chemists that open the door to novel probes and therapeutic agents Nucleic acids continue to gain importance as novel diagnostic and therapeutic agents. With contributions from noted scientists and scholars, Enzymatic and Chemical Synthesis of Nucleic Acid Derivatives is a practical reference that includes a wide range of approaches for the synthesis of designer nucleic acids and their derivatives. The book covers enzymatic (including chemo-enzymatic) methods, with a focus on the synthesis and incorporation of modified nucleosides. The authors also offer a review of innovative approaches for the non-enzymatic chemical synthesis of nucleic acids and their analogs and derivatives, highlighting especially challenging species. The book offers a concise review of the methods that prepare novel and heavily modified polynucleotides in sufficient amount and purity for most clinical and research applications. This important book: -Presents a timely and topical guide to the synthesis of designer nucleic acids and their derivatives -Addresses the growing market for nucleotide-derived pharmaceuticals used as anti-infectives and chemotherapeutic agents, as well as fungicides and other agrochemicals. -Covers novel methods and the most recent trends in the field -Contains contributions from an international panel of noted scientistics Written for biochemists, medicinal chemists, natural products chemists, organic chemists, and biotechnologists, Enzymatic and Chemical Synthesis of Nucleic Acid Derivatives is a practice-oriented guide that reviews innovative methods for the enzymatic as well as non-enzymatic synthesis of nucleic acid species.
Methods in Enzymology volumes provide an indispensable tool for the researcher. Each volume is carefully written and edited by experts to contain state-of-the-art reviews and step-by-step protocols. In this volume, we have brought together a number of core protocols concentrating on Cell, Lipid and Carbohydrate, complementing the traditional content that is found in past, present and future Methods in Enzymology volumes. - Indispensable tool for the researcher - Carefully written and edited by experts to contain step-by-step protocols - In this volume we have brought together a number of core protocols concentrating on Cell, Lipid and Carbohydrate
Das umfassende Referenzwerk zur Kinase-Forschung: Ausführlich werden die Themen Kinase-Engineering, Peptidsubstrat-Engineering, das Design von Co-Substraten und Kinasehemmer erläutert sowie deren Anwendung in der Bio- und Pharmaforschung beschrieben.
Good methods must be reliable, well-tested, and honed to minimize the time and expense required to achieve the desired results. CPNC provides a continuously growing and evolving set of protocols that allows researchers to benefit from the experience of other researchers around the world. The core manual provides a comprehensive set of protocols that have been compiled, revised, and streamlined over the last 6 years. Quarterly updates provide new protocols in emerging areas of research as well as continued advances and new applications for fundamental methods. The book is designed to grow and change with the field of nucleic acid chemistry. Fundamental nucleoside chemistry methods include sugar-base condensation, phosphorylation, and nucleoside protection. Methods for oligonucleotide synthesis include H-phosphonate and phosphoramidite approaches, solid-phase and solution-phase synthesis, large-scale synthesis, synthesis for modified and unmodified oligonucleotides, conjugation of oligonucleotides, synthesis without base protection, and synthesis on microarrays. More specialized synthetic methods include synthesis of biologically active nucleosides and prodrugs. Purification and characterization methods are detailed. Advanced methods include biophysical analysis, combinatorial methods, and nanotechnology. Each protocol includes rationale for choosing appropriate methods, step-by-step procedures, complete recipes, anticipated results, characterization data, and troubleshooting, as well as background and recommended reading. The level of procedural detail is far beyond that found in the research literature, and tips and comments from authors are geared towards ensuring reliable duplication in the laboratory.
The first book to offer a blueprint for overcoming the challenges to successfully quantifying biomarkers in living organisms The demand among scientists and clinicians for targeted quantitation experiments has experienced explosive growth in recent years. While there are a few books dedicated to bioanalysis and biomarkers in general, until now there were none devoted exclusively to addressing critical issues surrounding this area of intense research. Target Biomarker Quantitation by LC-MS provides a detailed blueprint for quantifying biomarkers in biological systems. It uses numerous real-world cases to exemplify key concepts, all of which were carefully selected and presented so as to allow the concepts they embody to be easily expanded to future applications, including new biomarker development. Target Biomarker Quantitation by LC-MS primarily focuses on the assay establishment for biomarker quantitation—a critical issue rarely treated in depth. It offers comprehensive coverage of three core areas of biomarker assay establishment: the relationship between the measured biomarkers and their intended usage; contemporary regulatory requirements for biomarker assays (a thorough understanding of which is essential to producing a successful and defendable submission); and the technical challenges of analyzing biomarkers produced inside a living organism or cell. Covers the theory of and applications for state-of-the-art mass spectrometry and chromatography and their applications in biomarker analysis Features real-life examples illustrating the challenges involved in target biomarker quantitation and the innovative approaches which have been used to overcome those challenges Addresses potential obstacles to obtain effective biomarker level and data interpretation, such as specificity establishment and sample collection Outlines a tiered approach and fit-for-purpose assay protocol for target biomarker quantitation Highlights the current state of the biomarker regulatory environment and protocol standards Target Biomarker Quantitation by LC-MS is a valuable resource for bioanalytical scientists, drug metabolism and pharmacokinetics scientists, clinical scientists, analytical chemists, and others for whom biomarker quantitation is an important tool of the trade. It also functions as an excellent text for graduate courses in pharmaceutical, biochemistry and chemistry.
Extensively revised and updated, Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition reflects the logarithmic progress made in the past four years of oligonucleotide-based therapies, and, in particular, antisense therapeutics and research. Interpreting lessons learned from the clinical trials of first generati
This book spans diverse aspects of modified nucleic acids, from chemical synthesis and spectroscopy to in vivo applications, and highlights studies on chemical modifications of the backbone and nucleobases. Topics discussed include fluorescent pyrimidine and purine analogs, enzymatic approaches to the preparation of modified nucleic acids, emission and electron paramagnetic resonance (EPR) spectroscopy for studying nucleic acid structure and dynamics, non-covalent binding of low- and high-MW ligands to nucleic acids and the design of unnatural base pairs. This unique book addresses new developments and is designed for graduate level and professional research purposes.
This volume provides relevant synthetic strategies, incorporation, and applications of non-natural nucleic acids. Chapters detail monomer synthesis, oligomer synthesis/construction, and applications allowing researchers to explore and determine which methodology or methodologies are relevant to their needs. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Non-Natural Nucleic Acids: Methods and Protocols aims to serve as a guide for researchers exploring their own inquiries and to provide a springboard for new endeavors.