Protein-protein interactions (PPI) are at the heart of the majority of cellular processes, and are frequently dysregulated or usurped in disease. Given this central role, the inhibition of PPIs has been of significant interest as a means of treating a wide variety of diseases. However, there are inherent challenges in developing molecules capable of disrupting the relatively featureless and large interfacial areas involved. Despite this, there have been a number of successes in this field in recent years using both traditional drug discovery approaches and innovative, interdisciplinary strategies using novel chemical scaffolds. This book comprehensively covers the various aspects of PPI inhibition, encompassing small molecules, peptidomimetics, cyclic peptides, stapled peptides and macrocycles. Illustrated throughout with successful case studies, this book provides a holistic, cutting-edge view of the subject area and is ideal for chemical biologists and medicinal chemists interested in developing PPI inhibitors.

Protein–protein interactions (PPI) are at the heart of the majority of cellular processes, and are frequently dysregulated or usurped in disease. Given this central role, the inhibition of PPIs has been of significant interest as a means of treating a wide variety of diseases. However, there are inherent challenges in developing molecules capable of disrupting the relatively featureless and large interfacial areas involved. Despite this, there have been a number of successes in this field in recent years using both traditional drug discovery approaches and innovative, interdisciplinary strategies using novel chemical scaffolds. This book comprehensively covers the various aspects of PPI inhibition, encompassing small molecules, peptidomimetics, cyclic peptides, stapled peptides and macrocycles. Illustrated throughout with successful case studies, this book provides a holistic, cutting-edge view of the subject area and is ideal for chemical biologists and medicinal chemists interested in developing PPI inhibitors.

With the most comprehensive and up-to-date overview of structure-based drug discovery covering both experimental and computational approaches, Structural Biology in Drug Discovery: Methods, Techniques, and Practices describes principles, methods, applications, and emerging paradigms of structural biology as a tool for more efficient drug development. Coverage includes successful examples, academic and industry insights, novel concepts, and advances in a rapidly evolving field. The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a valuable reference and resource that: Presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology Includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design Emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures Illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins

Given the immense progress achieved in elucidating protein-protein complex structures and in the field of protein interaction modeling, there is great demand for a book that gives interested researchers/students a comprehensive overview of the field. This book does just that. It focuses on what can be learned about protein-protein interactions from the analysis of protein-protein complex structures and interfaces. What are the driving forces for protein-protein association? How can we extract the mechanism of specific recognition from studying protein-protein interfaces? How can this knowledge be used to predict and design protein-protein interactions (interaction regions and complex structures)? What methods are currently employed to design protein-protein interactions, and how can we influence protein-protein interactions by mutagenesis and small-molecule drugs or peptide mimetics?The book consists of about 15 review chapters, written by experts, on the characterization of protein-protein interfaces, structure determination of protein complexes (by NMR and X-ray), theory of protein-protein binding, dynamics of protein interfaces, bioinformatics methods to predict interaction regions, and prediction of protein-protein complex structures (docking and homology modeling of complexes, etc.) and design of protein-protein interactions. It serves as a bridge between studying/analyzing protein-protein complex structures (interfaces), predicting interactions, and influencing/designing interactions.

New genomic information has revealed the crucial role that protein–protein interactions (PPIs) play in regulating numerous cellular functions. Aberrant forms of these interactions are common in numerous diseases and thus PPIs have emerged as a vast class of critical drug targets. Despite the importance of PPIs in biology, it has been extremely challenging to convert targets into therapeutics and targeting PPIs had long been considered a very difficult task. However, over the past decade the field has advanced with increasing growth in the number of successful PPI regulators. Protein–Protein Interaction Regulators surveys the latest advances in the structural understanding of PPIs as well as recent developments in modulator discovery.

This book comprehensively reviews the state-of-the-art strategies developed for protein-protein interaction (PPI) inhibitors, and highlights the success stories in new drug discovery and development. Consisting of two parts with twelve chapters, it demonstrates the design strategies and case studies of small molecule PPI inhibitors. The first part discusses various discovery strategies for small molecule PPI inhibitors, such as high throughput screening, hot spot-based design, computational approaches, and fragment-based design. The second part presents recent advances in small molecule inhibitors, focusing on clinical candidates and new PPI targets. This book has broad appeal and is of significant interest to the pharmaceutical science and medicinal chemistry communities.

Advances in chemistry, biology and genomics coupled with laboratory automation and computational technologies have led to the rapid emergence of the multidisciplinary field of chemical genomics. This edited text, with contributions from experts in the field, discusses the new techniques and applications that help further the study of chemical genomics. The beginning chapters provide an overview of the basic principles of chemical biology and chemical genomics. This is followed by a technical section that describes the sources of small-molecule chemicals; the basics of high-throughput screening technologies; and various bioassays for biochemical-, cellular- and organism-based screens. The final chapters connect the chemical genomics field with personalized medicine and the druggable genome for future discovery of new therapeutics. This book will be valuable to researchers, professionals and graduate students in many fields, including biology, biomedicine and chemistry.

Gabriel Waksman Institute of Structural Molecular Biology, Birkbeck and University College London, Malet Street, London WC1E 7HX, United Kingdom Address for correspondence: Professor Gabriel Waksman Institute of Structural Molecular Biology Birkbeck and University College London Malet Street London WC1E 7H United Kingdom Email: g. waksman@bbk. ac. uk and g. waksman@ucl. ac. uk Phone: (+44) (0) 207 631 6833 Fax: (+44) (0) 207 631 6833 URL: http://people. cryst. bbk. ac. uk/?ubcg54a Gabriel Waksman is Professor of Structural Molecular Biology at the Institute of Structural Molecular Biology at UCL/Birkbeck, of which he is also the director. Before joining the faculty of UCL and Birkbeck, he was the Roy and Diana Vagelos Professor of Biochemistry and Molecular Biophysics at the Washington University School of Medicine in St Louis (USA). The rapidly evolving ?eld of protein science has now come to realize the ubiquity and importance of protein–protein interactions. It had been known for some time that proteins may interact with each other to form functional complexes, but it was thought to be the property of only a handful of key proteins. However, with the advent of hi- throughput proteomics to monitor protein–protein interactions at an organism level, we can now safely state that protein–protein interactions are the norm and not the exception.

This book is indexed in Chemical Abstracts ServiceThe interactions of proteins with other molecules are important in many cellular activities. Investigations have been carried out to understand the recognition mechanism, identify the binding sites, analyze the the binding affinity of complexes, and study the influence of mutations on diseases. Protein interactions are also crucial in structure-based drug design.This book covers computational analysis of protein-protein, protein-nucleic acid and protein-ligand interactions and their applications. It provides up-to-date information and the latest developments from experts in the field, using illustrations to explain the key concepts and applications. This volume can serve as a single source on comparative studies of proteins interacting with proteins/DNAs/RNAs/carbohydrates and small molecules.

Connects fundamental knowledge of multivalent interactions with current practice and state-of-the-art applications Multivalency is a widespread phenomenon, with applications spanning supramolecular chemistry, materials chemistry, pharmaceutical chemistry and biochemistry. This advanced textbook provides students and junior scientists with an excellent introduction to the fundamentals of multivalent interactions, whilst expanding the knowledge of experienced researchers in the field. Multivalency: Concepts, Research & Applications is divided into three parts. Part one provides background knowledge on various aspects of multivalency and cooperativity and presents practical methods for their study. Fundamental aspects such as thermodynamics, kinetics and the principle of effective molarity are described, and characterisation methods, experimental methodologies and data treatment methods are also discussed. Parts two and three provide an overview of current systems in which multivalency plays an important role in chemistry and biology, with a focus on the design rules, underlying chemistry and the fundamental principles of multivalency. The systems covered range from chemical/materials-based ones such as dendrimers and sensors, to biological systems including cell recognition and protein binding. Examples and case studies from biochemistry/bioorganic chemistry as well as synthetic systems feature throughout the book. Introduces students and young scientists to the field of multivalent interactions and assists experienced researchers utilising the methodologies in their work Features examples and case studies from biochemistry/bioorganic chemistry, as well as synthetic systems throughout the book Edited by leading experts in the field with contributions from established scientists Multivalency: Concepts, Research & Applications is recommended for graduate students and junior scientists in supramolecular chemistry and related fields, looking for an introduction to multivalent interactions. It is also highly useful to experienced academics and scientists in industry working on research relating to multivalent and cooperative systems in supramolecular chemistry, organic chemistry, pharmaceutical chemistry, chemical biology, biochemistry, materials science and nanotechnology.