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Since the discovery of the DNA double helix in 1953, nucleic acids have formed the central theme of much of contemporary molecular science. Recent mastery of nucleic acids synthesis has been the key to the establishment of the biotechnology industry, and our improving knowledge of nucleic acid structures and interactions is considerably influencing the design of novel drugs. The first edition of this book responded to the pressing need for a single volume that integrated the chemistry and biology of the nucleic acids in an introductory yet authoritative text. This second and completely updated edition, which includes a new chapter on techniques applied to nucleic acids, sets the basics of the nucleic acids in the context of the expanding horizons set by modern structural biology, RNA enzymology, drug discovery and biotechnology.
The structure, function and reactions of nucleic acids are central to molecular biology and are crucial for the understanding of complex biological processes involved. Revised and updated Nucleic Acids in Chemistry and Biology 3rd Edition discusses in detail, both the chemistry and biology of nucleic acids and brings RNA into parity with DNA. Written by leading experts, with extensive teaching experience, this new edition provides some updated and expanded coverage of nucleic acid chemistry, reactions and interactions with proteins and drugs. A brief history of the discovery of nucleic acids is followed by a molecularly based introduction to the structure and biological roles of DNA and RNA. Key chapters are devoted to the chemical synthesis of nucleosides and nucleotides, oligonucleotides and their analogues and to analytical techniques applied to nucleic acids. The text is supported by an extensive list of references, making it a definitive reference source. This authoritative book presents topics in an integrated manner and readable style. It is ideal for graduate and undergraduates students of chemistry and biochemistry, as well as new researchers to the field.
Providing a comprehensive account of the structures and physical chemistry properties of nucleic acids, with special emphasis on biological function, this text has been organized to meet the needs of those who have only a basic understanding of physical chemistry and molecular biology.
Life in all its forms is based on nucleic acids which store and transfer genetic information. The book addresses main aspects of synthesis, hydrolytic stability and solution equilibria of nucleosides, nucleotides and oligonucleotides, as well as synthesis of their structural analogs that are of interest in chemotherapy. In addition, recent achievements in chemistry of catalytic nucleic acids, development of oligonucleotide based drugs and novel strategies for their targeting and delivery are discussed. The central theme always is the correlation of structure and function.
This book compiles recent research on the modification of nucleic acids. It covers backbone modifications and conjugation of lipids, peptides and proteins to oligonucleotides and their therapeutic use. Synthesis and application in biomedicine and nanotechnology of aptamers, fluorescent and xeno nucleic acids, DNA repair and artificial DNA are discussed as well.
Sequencing, cloning, transcription - these are but a few key techniques behind the current breathtaking advances in molecular biology and biochemistry. As these methods continuosly diversify, biochemists need a sound chemical understanding to keep the pace. Chemists beginning working in the molecular biology lab need an introduction to this field from their point of view. This book serves both: it describes most of the known chemical reactions of nucleosides, nucleotides, and nucleic acids in sufficient detail to provide the desired background, and additionally, the fundamental relations between sequence, structure and functionality of nucleic acids are presented. The first edition of this book, which was published in Russian, has immediately become a recognized standard reference. This second, thoroughly revised and updated edition, now published in English, is likely to achieve a similar position in the international scientific community.
New textbooks at all levels of chemistry appear with great regularity. Some fields like basic biochemistry, organic reaction mechanisms, and chemical ther modynamics are well represented by many excellent texts, and new or revised editions are published sufficiently often to keep up with progress in research. However, some areas of chemistry, especially many of those taught at the grad uate level, suffer from a real lack of up-to-date textbooks. The most serious needs occur in fields that are rapidly changing. Textbooks in these subjects usually have to be written by scientists actually involved in the research which is advancing the field. It is not often easy to persuade such individuals to set time aside to help spread the knowledge they have accumulated. Our goal, in this series, is to pinpoint areas of chemistry where recent progress has outpaced what is covered in any available textbooks, and then seek out and persuade experts in these fields to produce relatively concise but instructive introductions to their fields. These should serve the needs of one semester or one quarter graduate courses in chemistry and biochemistry. In some cases the availability of texts in active research areas should help stimulate the creation of new courses. CHARLES R. CANTOR New York Preface This monograph is based on a review on polynucleotide structures written for a book series in 1976.
This volume is comprised of 18 chapters, covering various aspects of DNA modification and RNA modified bases. It also discusses in detail circular RNA, therapeutic oligonucleotides and their different properties. The chemical nature of DNA, RNA, protein and lipids makes these macromolecules easily modifiable, but they are also susceptible to damage from both endogenous and exogenous agents. Alkylation and oxidation show a potential to disrupt the cellular redox equilibrium and cause cellular damage leading to inflammation and even chronic disease. Furthermore, DNA damage can drive mutagenesis and the resulting DNA sequence changes can induce carcinogenesis and cancer progression. Modified nucleosides can occur as a result of oxidative DNA damage and RNA turnover, and are used as markers for various diseases. To function properly some RNA needs to be chemically modified post-transcriptionally. Dysregulation of the RNA-modification pattern or of the levels of the enzymes that catalyze these modifications alters RNA functionality and can result in complex phenotypes, likely due to defects in protein translation. While modifications are best characterized in noncoding ribonucleic acids like tRNA and rRNA, coding mRNAs have also been found to contain modified nucleosides. This book is a valuable resource, not only for graduate students but also researchers in the fields of molecular medicine and molecular biology.
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.
Peptide nucleic acids (PNAs) have now existed for slightly more than ten years, with the interest in and applications of this pseudopeptide DNA mimic steadily increasing during the entire period. PNAs have rapidly attracted the attention of scientists from a diversity of fields ranging from (bio)organic and biophysical chemistry to prebiotic evolution, and from molecular biology to genetic diagnostics and drug development. Many of the applications take advantage of the unique properties of PNA—an uncharged pseudopeptide—that distinguish this DNA mimic from more traditional DNA analogs. Rather than trying to create a comprehensive collection of all published methods and protocols involving PNA—many of which have not yet been validated— I have decided to concentrate on select protocols that are either very well established by several groups around the world, such as PCR-clamping and in situ hybridization, or on new methods that may have broader future impact. Basic methods for PNA oligomer synthesis and analyses have also been included. I am very grateful to those friends and colleagues who have enthusiastically contributed their work, discussions, and writing, and thereby made this book possible. Peter E. Nielsen v Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix IINTRODUCTION 1 PNA Technology Peter E. Nielsen. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 II CHEMISTRY 2 Solid Phase Synthesis of PNA Oligomers Frederik Beck. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 3 Synthesis of PNA-Peptide Conjugates Satish Kumar Awasthi and Peter E. Nielsen. . . . . . . . . . . . . . . . . . 43 4 Parallel Synthesis of PNA-Peptide Conjugate Libraries Satish Kumar Awasthi and Peter E. Nielsen. . . . . . . . . . . . . . . . . .