Sequence-specific DNA binding ligands, amongst which triple helix forming oligonucleotides are the most efficient as yet, represent promising tools in a number of fields. One of their most promising applications is as antiviral tools: they can specifically target a viral gene, even if it is integrated into the host genome, and be used to specifically inactivate the viral gene or even destroy the cells harboring this gene. However, from science fiction to science there remains a gap; and we are at the moment on the threshold of this fascinating field. Triple Helix Forming Oligonucleotides considers the different aspects of the design and improvement, current or future, of these molecules and their structural analysis, as well as their applications, with special emphasis on the attempts to obtain biological effects of these potentially important tools. What emerges is that the current state of the research is encouraging, and that these molecules are already useful in some biotechnology applications.
Sequence-specific DNA binding ligands, amongst which triple helix forming oligonucleotides are the most efficient as yet, represent promising tools in a number of fields. One of their most promising applications is as antiviral tools: they can specifically target a viral gene, even if it is integrated into the host genome, and be used to specifically inactivate the viral gene or even destroy the cells harboring this gene. However, from science fiction to science there remains a gap; and we are at the moment on the threshold of this fascinating field. Triple Helix Forming Oligonucleotides considers the different aspects of the design and improvement, current or future, of these molecules and their structural analysis, as well as their applications, with special emphasis on the attempts to obtain biological effects of these potentially important tools. What emerges is that the current state of the research is encouraging, and that these molecules are already useful in some biotechnology applications.
There have been remarkable advances towards discovering agents that exhibit selectivity and sequence-specificity for DNA, as well as understanding the interactions that underlie its propensity to bind molecules. This progress has important applications in many areas of biotechnology and medicine, notably in cancer treatment as well as in future gene targeting therapies. The editor and contributing authors are leaders in their fields and provide useful perspectives from diverse and interdisciplinary backgrounds on the current status of this broad area. The role played by chemistry is a unifying theme. Early chapters cover methodologies to evaluate DNA-interactive agents and then the book provides examples of DNA-interactive molecules and technologies in development as therapeutic agents. DNA-binding metal complexes, peptide and polyamide–DNA interactions, and gene targeting tools are some of the most compelling topics treated in depth. This book will be a valuable resource for postgraduate students and researchers in chemical biology, biochemistry, structural biology and medicinal fields. It will also be of interest to supramolecular chemists and biophysicists.
A collection of powerful new techniques for oligonucleotide synthesis and for the use of modified oligonucleotides in biotechnology. Among the protocol highlights are a novel two-step process that yields a high purity, less costly, DNA, the synthesis of phosphorothioates using new sulfur transfer agents, the synthesis of LNA, peptide conjugation methods to improve cellular delivery and cell-specific targeting, and triple helix formation. The applications include using molecular beacons to monitor the PCR amplification process, nuclease footprinting to study the sequence-selective binding of small molecules of DNA, nucleic acid libraries, and the use of small interference RNA (siRNA) as an inhibitor of gene expression.
DNA Structure and Function, a timely and comprehensive resource, is intended for any student or scientist interested in DNA structure and its biological implications. The book provides a simple yet comprehensive introduction to nearly all aspects of DNA structure. It also explains current ideas on the biological significance of classic and alternative DNA conformations. Suitable for graduate courses on DNA structure and nucleic acids, the text is also excellent supplemental reading for courses in general biochemistry, molecular biology, and genetics. - Explains basic DNA Structure and function clearly and simply - Contains up-to-date coverage of cruciforms, Z-DNA, triplex DNA, and other DNA conformations - Discusses DNA-protein interactions, chromosomal organization, and biological implications of structure - Highlights key experiments and ideas within boxed sections - Illustrated with 150 diagrams and figures that convey structural and experimental concepts
A comprehensive review of contemporary antisense oligonucleotides drugs and therapeutic principles, methods, applications, and research Oligonucleotide-based drugs, in particular antisense oligonucleotides, are part of a growing number of pharmaceutical and biotech programs progressing to treat a wide range of indications including cancer, cardiovascular, neurodegenerative, neuromuscular, and respiratory diseases, as well as other severe and rare diseases. Reviewing fundamentals and offering guidelines for drug discovery and development, this book is a practical guide covering all key aspects of this increasingly popular area of pharmacology and biotech and pharma research, from the basic science behind antisense oligonucleotides chemistry, toxicology, manufacturing, to safety assessments, the design of therapeutic protocols, to clinical experience. Antisense oligonucleotides are single strands of DNA or RNA that are complementary to a chosen sequence. While the idea of antisense oligonucleotides to target single genes dates back to the 1970's, most advances have taken place in recent years. The increasing number of antisense oligonucleotide programs in clinical development is a testament to the progress and understanding of pharmacologic, pharmacokinetic, and toxicologic properties as well as improvement in the delivery of oligonucleotides. This valuable book reviews the fundamentals of oligonucleotides, with a focus on antisense oligonucleotide drugs, and reports on the latest research underway worldwide. • Helps readers understand antisense molecules and their targets, biochemistry, and toxicity mechanisms, roles in disease, and applications for safety and therapeutics • Examines the principles, practices, and tools for scientists in both pre-clinical and clinical settings and how to apply them to antisense oligonucleotides • Provides guidelines for scientists in drug design and discovery to help improve efficiency, assessment, and the success of drug candidates • Includes interdisciplinary perspectives, from academia, industry, regulatory and from the fields of pharmacology, toxicology, biology, and medicinal chemistry Oligonucleotide-Based Drugs and Therapeutics belongs on the reference shelves of chemists, pharmaceutical scientists, chemical biologists, toxicologists and other scientists working in the pharmaceutical and biotechnology industries. It will also be a valuable resource for regulatory specialists and safety assessment professionals and an important reference for academic researchers and post-graduates interested in therapeutics, antisense therapy, and oligonucleotides.
This book presents the latest knowledge on a broad range of topics relating to the synthesis of natural and artificial oligonucleotides with therapeutic potential. Nucleic acid-based therapeutics are attracting much attention, and numerous therapeutic oligonucleotides, such as antisense oligonucleotides, siRNAs, splice-switching oligonucleotides, and nucleic acid aptamers, are being evaluated in clinical trials for the treatment of a variety of diseases. Synthesis of Therapeutic Oligonucleotides covers a broad range of topics in the field that are of high relevance to researchers, including the synthesis of natural and chemically modified oligonucleotides, the development of novel nucleic acid analogs, industrial scale synthesis and purification of oligonucleotides, and important aspects of chemistry, manufacturing, and controls (CMC). The aim is to provide new insights and inspire fresh ideas in nucleic acid chemistry that may ultimately lead to novel concepts and techniques and the discovery of more effective nucleic acid drugs. The book will be of high value for both established researchers in the field and students intending to specialize in nucleic acid chemistry research.
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.
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.
The development of agents capable of cleaving RNA and DNA has attracted considerable attention from researchers in the last few years, because of the immediate and very important applications they can find in the emerging fields of biotechnology and pharmacology. There are essentially two classes of these agents - nucleases that occur naturally inside cells and synthetically produced artificial nucleases. The first class includes protein enzyme nucle ases and catalytic RNA structured ribozymes that perform cleavage of the phosphodiester bonds in nucleic acids according to a hydrolytic pathway in the course of different biochemical processes in the cell. A different pathway is used by some antibiotics which cleave DNA via redox-based mechanisms resulting in oxidative damage of nucleotide units and breakage of the DNA backbone. The above molecules are indispensable tools for manipulating nucleic acids and processing RNA; DNA-cleaving antibiotics and cytotoxic ribonucleases have demonstrated utility as chemotherapeutic agents. The second class, artificial nucleases, are rationally designed to imitate the active centers of natural enzymes by simple structures possessing minimal sets of the most important characteristics that are essential for catalysis. A dif ferent approach, in vitro selection, was also used to create artificial RNA and DNA enzymes capable of cleaving RNA. Being less efficient and specific as compared to the natural enzymes, the primitive mimics are smaller and robust and can function in a broad range of conditions.
