Preface

In the eleven years that have elapsed since the publication by the Royal Society of Chemistry of Sequence-specific DNA Binding Agents there have been notable advances in all areas of science pertaining to the chemistry behind the binding of small molecules to DNA. At the same time our understanding of the elements of molecular recognition at the level of nucleotide sequences has become increasingly important for drug discovery and development, not least in the treatment of cancer as well as other diseases that are of genetic origin. Accordingly, the present sequel represents an attempt to bring the reader up to speed with regard to advances in topics dealing with now well-established DNA binders and thus is a legitimate follow-up to the first edition, but now with its horizons greatly expanded through inclusion of an approximately equal number of wholly original chapters devoted to exciting new areas. Thus among the chapter updates that relate fairly directly to drug discovery we hear from David Graves about one of the earliest antibiotics actinomycin D which has saved great numbers of lives, Federico Gago on more antibiotics and drugs studied by computer simulations, Stephen Neidle on quadruplex-binding compounds, Bengt Norden on slow DNA binders, Keith Fox on triplex-forming oligonucleotides, Peter Nielsen on peptide nucleic acids, Yves Pommier on interfacial and topoisomerase inhibitors, and from Peter Dervan on synthetic polyamides designed specifically to target critical nucleotide sequences, such as those associated with prostate cancer. There is also an updated chapter from Brad Chaires expanded to describe new fluorescence methodology for studying drug–nucleic acid interactions, upon which he is a renowned expert. In response to reviewers of the first book as well as the remarks of many colleagues and keen advisors we have beefed up and coordinated topics like metal-based agents by including authoritative contributions from Jackie Barton and Christine Cardin. The field of peptide–DNA recognition, which has seen major advances in the past eleven years and offers equally great promise, is now represented by the inclusion of chapters from Annemieke Madder and Leung Sheh. Finally, the growing importance of finding treatments for dementia among our ageing populations receives mention from Ming-Hon Ho in his chapter on binding of small molecules to trinucleotide DNA repeats associated with neurodegenerative diseases, and the remarkable promise of the new CRISPR/Cas9 technology for genome editing in a brave new world is expounded by Thomas Bentin (a colleague of Peter Nielsen) who was kind enough to put his shoulder to the wheel at a late stage of writing. To all these stalwart authors as well as their collaborators duly acknowledged in the list of contributors, the editor and publishers offer their heartfelt gratitude and echo the sentiments expressed in the preface to the first edition reprinted below, namely that the wide compass of subject matter should 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 our day. Unifying it all is a clear message of the role played by good chemistry in solving those problems.

Michael J. Waring