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 contains the texts of the nineteen lectures presented at the NATO-ASI - FEBS Course on "DNA - ligand interactions: from drugs to proteins." The Advanced Study Institute (ASIl was held from August 30th to September 11th. 1986 in the Abbey of Fontevraud (France). The ASI was attended by 112 participants from a wide scientific horizon and from twentyone different countries. It was in some way a follow-up of the ASI held in Maratea. Italy in May 1981 and which was published in the NATO ASI Life Science series as volume 45. While much has been learned about the way the cellular machinery maintains and transmits the genetic heritage. as well as how these processes are regulated. little is Known about how the interactions between the various partners involved are taKing place. The interactions of drugs and proteins with nucleic acids are of evident importance in the understanding of these problems. The spectacular advances in recombinant DNA technology and the increased sophistication of biophysical techniques. in particular >:-ray diffraction and nuclear magnetic resonance. have created a scientific environment which is highly promising for the future of research in molecular biology. These advances permH the serious hope that biology on the molecular level may become a r-eality. Some of the contributions at the ASI presented the most recent advances in this e>:citing field.

Metal ions and metal complexes have long been recognized ascritically important components of nucleic acid chemistry, both inregulation of gene expression and as promising therapeutic agents.Understanding how metal complexes interact with DNA has become anactive research area at the interface between chemistry, molecularbiology and medicine. Metal Complex - DNA Interactions provides a comprehensiveoverview of this increasingly diverse field, presenting recentdevelopments and the latest research with particular emphasis onmetal-based drugs and metal ion toxicity. The text is divided intofour parts: Basic Structural and Kinetic Aspects: includes chapterson sequence-selective metal binding to DNA and thermodynamicmodels. Medical Applications: focuses on anticancer platinumdrugs, including discussions on DNA repair in antitumor effects ofplatinum drugs and photo-dynamic therapy. DNA-Recognition - Nucleases and Sensor: describesprobes for DNA recognition, artificial restriction agents,metallo-DNAzymes for metal sensing applications and metal iondependent catalysis in nucleic acid enzymes. Toxicological Aspects: deals with structural studies ofmercury–DNA interactions, chromium-induced DNA damage andrepair, and the effect of arsenic and nickel on DNAintegrity. This book will be a valuable resource for academic researchersand professionals from a range of pharmaceutical and chemicalindustries, particularly those involved in the development of newand less toxic anticancer metallo-drugs, and in the field ofenvironmental and toxicological chemistry.

The motivation for us to conceive this series of volumes on regulation was mainly our belief that it would be fun, and at the same time productive, to approach the subject in a way that differs from that of other treatises. We thought it might be interesting and instructive for both author and reader-to examine a particular area of investigation in a framework of many different problems. Cutting across the traditional boundaries that have separated the subjects in past volumes on regulation is not an easy thing to do-not because it is difficult to think of what interesting topics should replace the old ones, but because it is difficult to find authors who are willing to write about areas outside those pursued in their own laboratories. Anyone who takes on the task of reviewing a broad area of interest must weave together its various parts by picking up the threads from many different laboratories, and attempt to produce a fabric with a meaningful design. Finding persons who are likely to succeed in such a task was the most difficult part of our job. In the first volume of this treatise, most of the chapters dealt with the mechanisms of The second volume involved a somewhat regulation of gene expression in microorganisms. broader area, spanning the prokaryotic-eukaryotic border. Topics ranged from phage mor phogenesis to the role of gradients in development. The last volume-Volume 3A-con cerned hormones, as does this volume-Volume 3B.

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.

This text on protein-ligand interactions offers a selection of the most useful and easily applied methods and acts as a guide to the principal techniques used.