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Since most therapeutic efforts have been predominantly focused on pharmaceuticals that target proteins, there is an unmet need to develop drugs that intercept cellular pathways that critically involve nucleic acids. Progress in the discovery of nucleic acid binding drugs naturally relies on the availability of analytical methods that assess the eff
This volume consolidates the key methods for studying ligand-nucleic acid interactions into a convenient source. Techniques that are examined range from biophysical and chemical approaches to methods rooted in molecular and cell biology.
Learn vital information about drug-DNA interactions from Drug-DNA Interactions: Structures and Spectra, the only comprehensive book written about this topic. Understand the types of structural and bonding information that can be obtained using specific physico-chemical methods and discover how to design new drugs that are more effective than current treatments and have fewer side effects. Find detailed information about X-ray crystallography, NMR spectroscopy, molecular modeling, and optical spectroscopy such as UV-Visible absorption, fluorescence, circular dichroism (CD), flow linear dichroism (FLD), infrared (IR) and Raman spectroscopy.
This cutting-edge book surveys the current knowledge on the mode of action of the major classes of DNA-interactive antitumor agents, providing information that could be crucial for the discovery of new therapeutic substances. It is an important reference for molecular biologists, cancer researchers, biochemists, biophysicists, and pharmacologists.
One of the central problems in the study of the mechanism of DNA-ligand interactions is the existence and nature of sequence specificity with respect to the base pairs of DNA. The presence of such a specificity could be of particular significance because it might possibly mean the involvement of specific genes in the effectiveness of the different drugs. The elucidation of the factors responsible for the specificity could then be important for the development of compounds susceptible to contribute to the control of gene expression and also to the development of rationally conceived, improved new generations of effective and specific chemotherapeutic agents. Important recent achievements, experimental and theoretical, in the analysis of such sequence specificities open prospects for possible rapid progress in this field. The 23rd Jerusalem symposium was devoted to the exploration of these recent achievements in relation to many types of ligand, with special emphasis on antitumor drugs. All major types of interaction, intercalation, groove binding, covalent linking, coordination, have been considered. So was also the effect of the interaction on the structure and properties of the nucleic acids and the relationship between the interaction and biological or pharmacological activities. We feel that this Volume presents a relatively complete up-to-date account of the state of the art in this important field of research.
This book provides a detailed view of the molecular structures of DNA and RNA and how they are recognised by small molecules and proteins. Extensive source material is provided, including information on relevant web sites and computer programmes. The major methods of structural investigation for nucleic acids: X-ray crystallography, NMR, and molecular modelling are reviewed and their scope and limitations (in the context of nucleic acids) discussed. Also covered are the conformational features of nucleic acid building blocks, including a description of how base-pair morphologies are analysed; the structures of DNA double helices and helical oligonucleotides, emphasising current ideas on sequence-dependent structure; and DNA-DNA interactions, including triplexes and quadruplexes. The principles of RNA folding, ribosome, and ribozyme structure are also surveyed. Both covalent and non-covalent nucleic acid interactions with small molecules are described, with the emphasis on recognition principles and sequence specific gene recognition. The principles of protein - nucleic acid are covered, focussing on regulatory proteins. Nucleic Acid Structure and Recognition will therefore equip readers with a good understanding of all the important aspects of this major field. The Nucleic Acid Database (NDB) crystallographic and NMR structures for the nucleic acid structures described in the book are freely available through the Nucleic Acid Structure and Recognition website.
Natural biochemical processes are routinely being discovered in living cells that involve RNA. Some of these processes, such as RNA interference, are now being exploited for biotechnology and medicinal applications. DNA has also proven in recent years to be more than a passive storehouse of information. For example, non-B-form DNA structures formed by G-rich DNA have been shown to participate in the regulation of gene expression, a discovery that presents new possibilities for drug targets in the genome. The current quest to understand how nucleic acid functions at the most fundamental level requires that we have a detailed understanding of nucleic acid-metal ion interactions. Because RNA and DNA are polyanions the structure and biological function of these biopolymers depends strongly on their association with metal ions. While this intimate connection between metal ions and nucleic function has been appreciated for decades, the noncovalent and dynamic nature of these interactions has continually presented challenges to the development of accurate and quantitative descriptions. Over the past few years the development of solution state spectroscopic techniques and the achievement of high resolution X-ray crystal structures have provided tremendous insights into the nature of nucleic acid-metal ion interactions, including direct evidence for their importance in determining nucleic acid structure, from the dictation of folding pathways followed by large RNA molecules to the subtle modulation of DNA groove widths. This new book provides a comprehensive review of the experimental studies that define our current understanding of nucleic acid-metal ion interactions with a particular emphasis being placed on experimental biophysical studies. However, the book is not merely a current review of the literature, as original material and fresh perspectives on published results are also presented. Particularly noteworthy topics include: -The chapter by Williams and fellow workers which reviews information provided by x-ray crystal structures and discusses what this information has revealed about the unique nature of Mg2+ interactions with RNA phosphate groups. The authors provide fresh insights, based upon structural comparisons, for how these interactions govern the local folding pathways of RNA. By dedicating separate chapters to the participation of metal ions in the kinetics and thermodynamics of RNA folding, this volume provides a more in depth treatise of both areas than is typically possible for reviews in which these two related, but distinct, topics are combined -Polyelectrolyte models of nucleic acids have proven to be extremely valuable for understanding the sequestering counterions in a so-called diffuse cloud around polymeric DNA. J. Michael Schurr provides a comprehensive review of polyanion models. Despite the success of polyelectrolyte models in describing some physical properties of nucleic acids, this topic is not always sufficiently understood by many researchers to make use of these models and this chapter serves as a valuable and up to date introduction to this topic. -The chapter by Pizarro and Sadler on metal ion-nucleic acid interactions in disease and medicine is complemented by a chapter by Lippert on coordinative bond formation between metal ions and nucleic acid bases. Together, these two chapters provide an overview of transition metal ion interactions with nucleic acids that illustrates the promise and peril that is associated with direct metal ion coordination to nucleic acid bases in living cells. The book is sufficiently detailed to serve as a reference source for researchers active in the field of nucleic acids biophysics and molecular biology. In addition, chapter authors have added introductory material and enough background material in each chapter so that the book can also can serve as an entry point for students and researchers that have not previously worked in the field which will make the book of lasting value and more accessible by a wider audience.
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.
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.
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.