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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.
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.
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Synthesis and Applications of DNA and RNA discusses the significant contributions in the development of synthetic routes to DNA and RNA. This book contains nine chapters that describe the complexities in the chemistry and biology of DNA and RNA. After briefly dealing with the various stages of development in the chemical synthesis of polynucleotides, this book goes on presenting the DNA synthesis on solid supports and through the phosphoramidite method on silica supports. The discussions then shift to the chemical-enzymatic synthesis of expressed genes; the biochemical aspects of chemical syntheses of oligoribonucleotides; and the methods of rapid DNA and RNA sequence analysis. A chapter specifically tackles the protocols of DNA synthesis using double-stranded plasmid DNA as a template. The final chapter deals with the use of oligonucleotides for the identification and isolation of specific gene sequences. This chapter also covers the use oligonucleotides in the detection of human genetic diseases. Biologists, geneticists, and researchers interested in DNA and RNA synthesis will find this work invaluable.
DNA polymerases synthesize DNA, the essential biomolecule responsible for encoding the complex information necessary for life, with remarkable efficiency and fidelity. Chemists and biologists have exploited this extraordinary enzyme to develop a wide range of biotechnological tools, including but certainly not limited to PCR and Sanger sequencing. While these landmark applications continue to be relied upon to this day, they represent only a small fraction of the possible uses of these enzymes. Here, I detail my work to expand the scope of the enzymatic synthesis of DNA in two distinct fields. Chapters 2-5 detail efforts to identify replicable candidate unnatural base pairs to expand the genetic alphabet from the natural four base code to an expanded six base code. Using a wide range of techniques, including chemical synthesis, directed evolution of DNA polymerases, and screening based methodologies, the d 5SICS:d MMO2 base pair is identified, resulting in our strongest candidate base pair identified to date. Chapter 6 details the use of an activity based phage display system to identify a DNA polymerase that possesses improved recognition of substrates applicable in next generation sequencing applications.
The First volume gives an overview of the enzymes involved in DNA synthesis and modification; the second volume deals with the RNA-enzymes. Although the major emphasis of the book is on eukaryotic enzymes, a separate chapter dealing with prokaryotic DNA repair enzymes has been included to discuss the major advances in this field in recent years. There are two separate chapters on RNA polymerases to provide a comprehensive coverage of the enzymes from lower eukaryotes, plants and higher eukaryotes.