Chemical Biology - Böcker

Glycans play a vital role in modulating protein structure and function from involvement in protein folding, solubility and stability to regulation of tissue distribution, recognition specificity, and biological activity. They can act as both positive and negative regulators of protein function, providing an additional level of control with respect to genetic and environmental conditions.Due to the complexity of glycosylated protein forms, elucidating structural and functional information has been challenging task for researchers but recent development of chemical biology-based tools and techniques is bridging these knowledge gaps. This book provides a thorough review of the current state of glycoprotein chemical biology, describing the development and application of glycoprotein and glycan synthesis technologies for understanding and manipulating protein glycosylation.

High throughput screening remains a key part of early stage drug and tool compound discovery, and methods and technologies have seen many fundamental improvements and innovations over the past 20 years. This comprehensive book provides a historical survey of the field up to the current state-of-the-art. In addition to the specific methods, this book also considers cultural and organizational questions that represent opportunities for future success.Following thought-provoking foreword and introduction from Professor Stuart Schreiber and the editors, chapters from leading experts across academia and industry cover initial considerations for screening, methods appropriate for different goals in small molecule discovery, newer technologies that provide alternative approaches to traditional miniaturization procedures, and practical aspects such as cost and resourcing. Within the context of their historical development, authors explain common pitfalls and their solutions.This book will serve as both a practical reference and a thoughtful guide to the philosophy underlying technological change in such a fast-moving area for postgraduates and researchers in academia and industry, particularly in the areas of chemical biology, pharmacology, structural biology and assay development.

Mass spectrometry is one of the most widespread technologies in chemistry and has been increasingly used in biology with the rise of omics sciences. This book summarizes some important methodological approaches in mass spectrometry and applications in the field of chemical biology. The core chapters build on basic concepts introduced in the opening chapter and explore established fields such as high throughput screening, proteomics and metabolomics. Emerging applications of mass spectrometry in elucidating biosynthetic pathways, enzyme mechanisms and protein-protein interactions are then presented. Connections between these diverse research fields are highlighted throughout. The book concludes with a discussion of databases and future perspectives. This book will be a useful tool to early chemical biology researchers wishing to incorporate mass spectrometry as a tool in their research.

Cyclic peptides are increasingly employed as chemical tools in biology and drug discovery. They have gained a lot of interest as alternative sources of new drugs to traditional small molecules. This book introduces cyclic peptides and provides a thorough overview of biosynthetic and fully synthetic approaches to their preparation. Following an introduction to cyclic peptides, biosynthetic and traditional chemical routes to cyclic peptides are reviewed. Due to their size, their synthesis is not trivial. Recent advances in the incorporation of novel structural units are presented in addition to how synthesis and biological methods can be combined. The chemical analysis of this molecular class is also discussed. Furthermore, chapters detail the progression of cyclic peptides as tools in biology and as potential drugs, providing a future vision of their importance.In total, this book provides the reader with a comprehensive view of the state-of-the-art of cyclic peptides, from construction to possible clinical utility. This book will be an essential resource for students, researchers and  scientists within industry in medicinal, bioorganic, natural product and analytical chemistry fields.

The rapid development of efficient computational tools has allowed researchers to tackle biological problems and to predict, analyse and monitor, at an atomic level, molecular recognition processes. This book offers a fresh perspective on how computational tools can aid the chemical biology research community and drive new research.Chapters from internationally renowned leaders in the field introduce concepts and discuss the impact of technological advances in computer hardware and software in explaining and predicting phenomena involving biomolecules, from small molecules to macromolecular systems. Important topics from the understanding of biomolecules to the modification of their functions are addressed, as well as examples of the application of tools in drug discovery, glycobiology, protein design and molecular recognition. Not only are the cutting-the-edge methods addressed, but also their limitations and possible future development.For anyone wishing to learn how computational chemistry and molecular modelling can provide information not easily accessible through other experimental methods, this book will be a valuable resource. It will be of interest to postgraduates and researchers in the biological and chemical sciences, medicinal and pharmaceutical chemistry, and theoretical chemistry.

Protein crystallography has become vital to further understanding the structure and function of many complex biological systems. In recent years, structure determination has progressed tremendously however the quality of crystals and data sets can prevent the best results from being obtained. With contributions from world leading researchers whose software are used worldwide, this book provides a coherent approach on how to handle difficult crystallographic data and how to assess its quality. The chapters will cover all key aspects of protein crystallography, from instrumentation and data processing through to model building. This book also addresses challenges that protein crystallographers will face such as dealing with data from microcrystals and multi protein complexes. This book is ideal for both academics and researchers in industry looking for a comprehensive guide to protein crystallography.

This book describes the events of primary energy transduction in life processes. Life as we know it depends on pumping protons across membranes. New tools to study the protein complexes involved has led to recent intensified progress in the field. Primary Energy Transduction in Biology focusses on recent structural results and new biophysical insights. These have been made possible by recent advances in high-resolution protein structures, in physical techniques to study reactions in real time, and in computational methods to study and refine both structures and their dynamics. Written and edited by leading experts, chapters discuss the latest key questions in cell respiration, photosynthesis, bioenergetics, proton transfer, electron transfer and membrane transport.Biochemists, biophysicists and chemical biologists will find this book an essential resource for a complete understanding of the molecular machines of bioenergetics.

Synthetic chemistry plays a central role in many areas of chemical biology; utilising recent case studies, the goal of Chemical and Biological Synthesis is to highlight the full impact that the preparation of novel reagents can have in chemical biology. Covering the synthetic approaches that can be applied across the whole field of chemical biology, this book provides synthetic chemists with the broader context to which their work contributes and the biological questions that can be addressed through it. An ideal guide for postgraduate students and researchers in synthetic organic chemistry and chemical biology, Chemical and Biological Synthesis introduces synthetic techniques and methods to those who wish to incorporate synthesis for the first time in their biology-focused research programmes.

The formation of disulphide bonds is probably the most influential modification of proteins. These bonds are unique among post-translational modifications of proteins as they can covalently link cysteine residues far apart in the primary sequence of a protein. This has the potential to convey stability to otherwise marginally stable structures of proteins. However, the reactivity of cysteines comes at a price: the potential to form incorrect disulphide bonds, interfere with folding, or even cause aggregation. An elaborate set of cellular machinery exists to catalyze and guide this process: facilitating bond formation, inhibiting unwanted pairings and scrutinizing the outcomes. Only in recent years has it become clear how intimately connected this cellular machinery is with protein folding helpers, organellar redox balance and cellular homeostasis as a whole.This book comprehensively covers the basic principles of disulphide bond formation in proteins and describes the enzymes involved in the correct oxidative folding of cysteine-containing proteins. The biotechnological and pharmaceutical relevance of proteins, their variants and synthetic replicates is continuously increasing. Consequently this book is an invaluable resource for protein chemists involved in realted research and production.

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.

Glycans play essential roles in diverse biological and etiological processes and their structural complexity endow various functions. The glycome is the entire set of glycans produced by an individual organism. As the glycan microarray emerged, a good amount of knowledge has been obtained in understanding the functions of glycans. However, limited accessibility of glycans is a major obstacle to the functional glycomics study. Although isolation from biology samples provided some structures, the low abundance of glycans obtained and the difficulty in complete structural assignment restricted the subsequent assay. To circumvent this limitation, many synthetic strategies, including chemical, enzymatic and chemo-enzymatic ones have been developed to make libraries of structurally defined complex glycans available. The glycans provided by these techniques combined with high-throughput glycoarray techniques have broadened and deepened our understanding about functional glycomics. The aim of this book is to provide a comprehensive review of the current state of the synthetic glycome and a brief introduction of the application of the synthetic glycome in glycoarray assay. Accordingly, synthetic strategies toward generating glycans with comprehensive structures as well as the glycoarrays to unveil the glycan functions are described in this book.

To thrive, every living cell must continuously gauge and respond to changes in its environment. These changes are ultimately implemented by modulating gene expression, a process that relies on transcription by Nature’s most multivalent molecular machine, the RNA polymerase. This book covers progress made over the past decade understanding how this machine functions to compute the cellular state, from the atomistic structural level responsible for chemistry to the integrative level at which RNA polymerase interacts with the other key molecular machineries of the cell.

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.

Numerous genetic methods can be utilised to link a phenotype to a single molecular target but annotated small molecule chemical probes and even entire chemogenomic libraries are increasingly being used as a complementary approach. This book will comprehensively cover the state of the art in chemical probes and best practice for use in target discovery, illustrated throughout with examples. Ideal for students and established biochemists, the book will also cover new technologies for probe discovery, new probe modalities, the new field of probes for RNA targets and the mature field of kinase chemical probes.

How life originated from the inanimate mixture of organic and inorganic compounds on the priomordial earth remains one of the great unknowns in science. This origin of life, or abiogenesis, continues to be examined in the context of the conditions and materials required for natural life to have begun on Earth both theoretically and experimentally. This book provides a broad but in-depth analysis of the latest discoveries in prebiotic chemsitry from the microscopic to the macroscopic scale; utilising experimental insight to provide a bottom up approach to plausibly explaining how life arose. With contributions from global leaders, this book is an ideal reference for postgraduate students and a single source of comprehensive information on the latest technical and theoretical advancements for researchers in a variety of fields from astrochemistry and astrophysics to organic chemistry and evolution.

The DNA of all organisms is constantly being damaged by endogenous and exogenous sources. Oxygen metabolism generates reactive species that can damage DNA, proteins and other organic compounds in living cells. Exogenous sources include ionizing and ultraviolet radiations, carcinogenic compounds and environmental toxins among others. The discovery of multiple DNA lesions and DNA repair mechanisms showed the involvement of DNA damage and DNA repair in the pathogenesis of many human diseases, most notably cancer. These books provide a comprehensive overview of the interdisciplinary area of DNA damage and DNA repair, and their relevance to disease pathology. Edited by recognised leaders in the field, this two-volume set is an appealing resource to a variety of readers including chemists, chemical biologists, geneticists, cancer researchers and drug discovery scientists.

This book provides a comprehensive overview of multimodal and combined techniques used for imaging applications in Chemical Biology, including afterglow luminescence imaging, chemiluminescence imaging, delayed fluorescence imaging, AIE fluorescence imaging, and many more techniques. As well as providing in-depth detail on the application of these techniques, the advantages and disadvantages of each are also discussed. Additionally, Imaging Tools for Chemical Biology also covers the use of chemical probes for tagging biomolecules and therapeutic applications. The current state of the art in biological imaging and future directions for the field are also discussed and evaluated. This book is a valuable resource and ideal for researchers new to the area, as well as experienced chemists interested in developing probes and biologists interested in utilising probes in their research.

The total synthesis of structurally complex natural products has challenged and inspired generations of chemists. However, despite their history as privileged bioactivity-rich scaffolds, the use of natural products in drug discovery has waned.Recent developments in biocatalysis have resulted in the application of enzymes for the construction of complex molecules. This dynamically developing field is increasingly becoming a competitive alternative for classical total synthesis. Giving readers an in-depth overview of the current state of the field, this book will be of wide interest to natural products and drug researchers with a chemical or biochemical background and biocatalysis experts in academia and industry.Chapters include emerging enzymes from biosynthetic pathways, enzymes for building block synthesis and late-stage derivatisation as well as the formation of specific structural elements, such as chiral amines and heterocycles. Other important aspects for the efficient chemoenzymatic synthesis of bioactive molecules include the development of multi-enzyme cascades, engineered enzymes and strategic considerations for the use of biocatalysts in the synthesis of natural products and synthetic drugs.

This volume aims to provide an in-depth view of the complete biochemistry of sulfur with an emphasis on aspects not covered elsewhere. Given its role in the formation of proteins and presence in the amino acids methionine and cysteine, sulfur is essential to life. Current literature on the biochemistry of sulfur is vast and widely dispersed, as such this volume is intended as a single-source for everything concerning sulfur biochemistry from metabolic roles of inorganic sulfur, to thiol and thioether chemical biology, to the university of cysteine chemistry in proteomes. Authored by a renowned biochemist and experienced writer and educator, this book is ideal for students and researchers in biochemistry, biology and the life sciences with an interest in sulfur and its role in life.

Circadian rhythms have been shown to be ubiquitous and critically important in the experimental laboratory, accounting for the difference between life and death in response to identical stimulus. The partly endogenous nature of circadian rhythms has been well documented and methods for their characterisation have been developed enabling the cellular and molecular mechanisms to be understood. Chronobiology and Chronomedicine aims to provide a review of these mechanisms underlying circadian rhythms and illustrate the role of the brain’s suprachiasmatic nuclei in the ‘pace-making’ process and the effects caused by ‘clock genes’ present in almost all cells. Beyond the mechanisms involved, the book discusses the relationship between body systems, disease, and proper circadian function; in particular, how disruption of the circadian rhythm is associated with ill health and disease status from observations made at the organismic level. The book is organised to be an ideal introduction for the postgraduate in various fields, reviewing developments and outlining methods to show the depth and breadth of chronobiology and chronomedicine, as well as an invaluable companion to researchers and healthcare professionals working in the field with an interest in developing novel therapeutic approaches.

Alexander Todd, the 1957 Nobel laureate in chemistry is credited with the statement: “where there is life, there is phosphorus”. Phosphorus chemical biology underlies most of life’s reactions and processes, from the covalent bonds that hold RNA and DNA together, to the making and spending 75 kg of ATP every day, required to run almost all metabolic and mechanical events in cells. Authored by a renowned biochemist, The Chemical Biology of Phosphorus provides an in-depth, unifying chemical approach to the logic and reactivity of inorganic phosphate and its three major derivatives (anhydrides, mono- and diesters) throughout biology to examine why life depends on phosphorus. Covering the breadth of phosphorus chemistry in biology, this book is ideal for biochemistry students, postgraduates and researchers interested in the chemical logic of phosphate metabolites, energy generation, biopolymer accumulation and phosphoproteomics.

The DNA of all organisms is constantly being damaged by endogenous and exogenous sources. Oxygen metabolism generates reactive species that can damage DNA, proteins and other organic compounds in living cells. Exogenous sources include ionizing and ultraviolet radiations, carcinogenic compounds and environmental toxins among others. The discovery of multiple DNA lesions and DNA repair mechanisms showed the involvement of DNA damage and DNA repair in the pathogenesis of many human diseases, most notably cancer. These books provide a comprehensive overview of the interdisciplinary area of DNA damage and DNA repair, and their relevance to disease pathology. Edited by recognised leaders in the field, this two-volume set is an appealing resource to a variety of readers including chemists, chemical biologists, geneticists, cancer researchers and drug discovery scientists.

The DNA of all organisms is constantly being damaged by endogenous and exogenous sources. Oxygen metabolism generates reactive species that can damage DNA, proteins and other organic compounds in living cells. Exogenous sources include ionizing and ultraviolet radiations, carcinogenic compounds and environmental toxins among others. The discovery of multiple DNA lesions and DNA repair mechanisms showed the involvement of DNA damage and DNA repair in the pathogenesis of many human diseases, most notably cancer. These books provide a comprehensive overview of the interdisciplinary area of DNA damage and DNA repair, and their relevance to disease pathology. Edited by recognised leaders in the field, this two-volume set is an appealing resource to a variety of readers including chemists, chemical biologists, geneticists, cancer researchers and drug discovery scientists.

From DNA and RNA to proteins and vitamins the role of nitrogen is central in organismal metabolism. The Chemical Biology of Nitrogen comprehensively examines how the chemistry available to both inorganic and organic nitrogen compounds both enable and conditions the vast array of nitrogen biologies. This book provides a chemocentric approach to both the inorganic and organic chemical biology of nitrogen. Following an introduction to nitrogen trivalency the book progresses through the logic of inorganic nitrogen metabolism and organic nitrogen metabolites to nitrogen proteomics with an integrative approach to understanding the role of nitrogen in its many biologic roles. Authored by a renowned scientist and educator, this book is ideal for researchers in chemical biology and nitrogen metabolism and will be of particular interest to advanced students and postgraduates in biochemistry and chemical biology.

Antibiotic resistance is a global health concern. Strains of pathogenic microorganisms that have developed resistance to multiple antibiotics, such as MRSA, are extremely difficult to treat, and alternative methods for tackling pathogenic microorganisms are in demand. One potential target for new therapeutics is inhibition of quorum sensing: how microorganisms communicate and form biofilms in a density-dependent manner. Inhibiting this system via ‘quorum quenching’ (QQ) is a promising route to new pharmaceuticals and for controlling biofilm formation and growth. Quorum sensing also provides interesting possibilities in synthetic biology for producing novel products, biosensors, bioactive molecules, and so on.This book covers the biology of quorum sensing and quenching, and potential sources of QQ enzymes and other inhibitors, as well as an overview of their mechanism and potential biotech applications. The book also covers the potential for new drug development from QQ, covering a range of related topics including protein engineering, imaging and computational studies, and integrated systems. This book is an ideal companion to researchers in chemical biology and medicinal chemistry, particularly those interested in biofilm formation, quorum sensing, novel antimicrobial development, synthetic biology and enzymology.