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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.
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 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.
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.
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.
Composed of contributions from experts in the chemical and biological sciences, it explores host-guest molecular interactions leading to the formation of molecular assemblies containing two or more species. Exciting applications are emerging in this field and it is expected that improved understanding of the interactions in synthetic host molecule complexes will lead to a better understanding of the more complex biological systems. Topics include biomimetic chemistry, preorganization, self-assembly, template-directed synthesis, antibiotic binding to peptides and DNA, interactions between proteins and other molecules.
The development of molecules that selectively bind to nucleic acids has provided many details about DNA and RNA recognition. The range of such substances, such as metal complexes, peptides, oligonucleotides and a wide array of synthetic organic compounds, is as manifold as the functions of nucleic acids. Nucleic acid recognition sequences are often found in the major or minor groove of a double strand, while other typical interactions include intercalation between base pairs or the formation of triple or quadruple helices. One example of a binding mode that has recently been proposed is end stacking on such complex structures as the telomere tetraplex. In this comprehensive book, internationally recognized experts describe in detail the important aspects of nucleic acid binding, and in so doing present impressive approaches to drug design. Since typical substances may be created naturally or synthetically, emphasis is placed on natural products, chemical synthesis, the use of combinatorial libraries, and structural characterization. The whole is rounded off by contributions on molecular modeling, as well as investigations into the way in which any given drug interacts with its nucleic acid recognition site.
Each volume of Advances in Pharmacology provides a rich collection of reviews on timely topics. Emphasis is placed on the molecular basis of drug action, both applied and experimental.
DNA sequence specificity is a sub-specialty in the general area of molecular recognition. This area includes macromolecular-molecular interactions (e.g., protein-DNA), oligomer-DNA interacitons (e.g., triple strands), and ligand-DNA interactions (e.g., drug-DNA). It is this latter group of DNA sequence specificity interactions that is the subject of Volumes 1 and 2 of Advances in DNA Sequence Specific Agents. As was the case for Volume 1, Part A also covers methodology, but in Volume 2 we include calorimetric titrations, molecular modeling, X-ray crystallographic and NMR structural studies, and transcriptional assays. Part B also follows the same format as Volume 1 and describes the sequence specificities and covalent and noncovalent interactions of small ligands with DNA.This volume is aimed in general at scientists who have an interest in deciphering the molecular mechanisms for sequence recognition of DNA. The methods have general applicability to small molecules as well as oligomers and proteins, while the examples provide general principles involved in sequence recognition.