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.

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.

This volume covers both the basic concepts and theory of bio-macromolecules under pressure and the various frontiers in high-pressure bioscience and biotechnology. A century has passed since Bridgman discovered the irreversible coagulation of egg white by applying pressure at 700 atmospheres in 1914. Today we are able to monitor pressure-dependent changes in protein structure as a reversible process even at atomic scale with modern spectroscopic techniques. We can study the fluctuating reality of protein structures as designed by nature, which is the basis for all dynamism of life on earth. We are currently facing a new era of high-pressure bioscience, in which pressure is no longer an “odd” or “foreign” variable to life, but rather an integrated part of it. Pressure is used as a crucial variable for disclosing the secrets of nature and as a powerful new tool for enhancing certain reactions in bio-macromolecules and even in living cells for our practical and industrial needs. A dramatic advancement of high-pressure bioscience both in the basic and the applied sciences is thus anticipated in near future, for which sharing the current advanced knowledge on structure and dynamics of bio-macromolecules under pressure among researchers in both fields is crucial. This book serves as a valuable resource not only for those working directly in a pressure-related field, but also for those working in many other fields of the biosciences. Particularly, the basic part of it is intended to serve as a classical text book on high-pressure bioscience to a wide audience including students and researchers in both basic and applied fields in years to come. Readers can focus on topics of immediate interest first, but may wish to go over other chapters if interest arises in a later occasion.

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 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.

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.

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.