Preface to Sequence-specific DNA Binding Agents Free

Twenty or thirty years ago the concept of gene targeting as a means of alleviating disease began to gain currency, whereas it had previously been little more than a pipe dream. Thanks to huge strides in our understanding of basic biology and medicine the concept is no longer a dream but an attainable goal. The talents of traditional biologists and geneticists, but perhaps above all chemists and biochemists, have conspired to create a climate in which the fruits of current research on DNA and gene function are clearly pointing the way to new therapies that will continue the revolutionary progress of chemotherapy as a prime modality for treating cancer. For much of cancer treatment to date has had to rely on drug interactions with DNA, and that is the principal area of medicine that has stimulated research on DNA binders (though it has to be acknowledged that such drugs can find useful employ in other areas of biotechnology and medical science as well). This book represents an attempt to summarise and illustrate some key aspects of the remarkable progress that has been made towards understanding how drugs can bind specifically to nucleic acids, and thus underpin the endeavour to make gene targeting a reality. The brief was to assemble a set of chapters written by senior scientists, who are acknowledged experts in the field, dealing with diverse aspects of the binding of antibiotics and drugs to DNA. Because of the importance of such substances in medicine, perhaps particularly the treatment of cancer, there are chapters that deal with established agents like actinomycin D, the first antibiotic found to be useful for cancer treatment, which is still in use today and forms the subject of chapter 6. After 60 years we are still learning new and surprising things about this remarkable antibiotic. The necessarily historical emphasis of this contribution is complemented by a rare and reflective chapter that describes the coming of age of theoretical and computational studies devoted to understanding how drugs interact specifically with DNA. Then there are contributions focussing on novel agents that show fairly immediate promise for the future of chemotherapy, notably topoisomerase inhibitors, telomerase inhibitors, peptide nucleic acids and triple helix-forming oligonucleotides. Research success is critically dependent upon advances in experimental methodology, so there is an important place for descriptions of new approaches that originate from the study of slow kinetics, melting curve analysis and improvements in classical medicinal chemistry brought about by discoveries originating from sophisticated forays into structural chemistry.

The book concludes with a thoughtful chapter on nucleic acid structures, mostly RNA, that might in due course become important targets for drug action.

The topics chosen by several authors are unique, or almost so, in cutting across the standard divisions of the discipline to provide a novel perspective. As a result, some areas, such as topoisomerase inhibitors and telomerase inhibitors, establish a framework that allows treatment by several different authors in a complementary manner. This may lead to occasional ‘overlap’ in information content, but has the inestimable virtue of furnishing a varied overview of progress in research from diverse points of view. The reader who progresses systematically through the text will be rewarded with some prime examples of how science works, through glimpses of the story of topoisomerase or telomerase inhibitors all the way from theory to drug development.

This wide compass of subject matter is a feature that may commend the book to students, established research workers, teachers and even historians of science. It is hoped that everyone will find something new and stimulating to read, set within the context of a coherent and multi-faceted attack upon some of the most pressing medical problems of the day. Unifying it all is a clear message of the role played by good chemistry in solving those problems.