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Amino Acids, Peptides and Proteins is a broad ranging title comprising a selection of comprehensive and critical reviews of significant developments at the biology and chemistry interface. Compiled by leading researchers in their subject, this volume incorporates current trends and emerging areas reflecting the state-of-the-art research in this field. Appealing broadly to researchers in academia and industry, it will be of great benefit to any researcher wanting a succinct reference in this field and looking at the future.

The phytochemical constituents of plants fall into two main categories based on their role in basic metabolic processes: primary and secondary. Primary metabolites are involved in basic life functions and are similar in all living cells, whereas secondary metabolites are derived from subsidiary pathways. Although traditionally referred to as secondary metabolites, more recently these compounds have been termed ‘plant specialized metabolites', as the exact biochemical boundary between primary and secondary metabolites has not been fully established. Plant specialized metabolites are the main elements in the study and use of ‘medicinal'plants and herbs, as well as in nutrition and food chemistry. In modern medicine, plant specialized metabolites provide many of the lead compounds in the production of medicines targeted at treating a broad variety of diseases. Such metabolites also play an important role in sessile plants to resist and withstand different biotic and abiotic stresses. Plant specialized metabolites are classified according to their chemical structures and this book will present the different classes in turn, while discussing their sources and distribution in plant families, their biosynthetic pathways, and their important and notable uses in phytochemistry and pharmacology. Chemical Diversity of Plant Specialized Metabolites will be a useful guide and reference point for chemists and students in many disciplines including synthetic organic chemists, medicinal chemists, plant scientists, pharmacognosists, chemical ecologists, bioengineers, and synthetic biologists, in addition to those working in related fields.

Authored by leading experts in the enzymology of natural product biosynthesis, this completely revised and updated edition provides a description of the types of natural products, the biosynthetic pathways that enable the production of these molecules, and an update on the discovery of novel products in the post-genomic era. Although some 500 000 – 600 000 natural products have been isolated and characterized over the past two centuries, there may be a 10-fold greater inventory awaiting immediate exploration based on biosynthetic gene cluster predictions. The approach of this book is to codify the chemical logic that underlies each natural product structural class as they are assembled from building blocks of primary metabolism. This second edition integrates many new findings into the sets of principles of the first edition that parsed categories of natural product chemistries into the underlying enzymatic mechanisms and the catalytic machinery for building the varied and complex end product metabolites. New chapters include evaluation of a core set of thermodynamically activated but kinetically stable metabolites that power both primary and secondary metabolic pathways. Also, after decades of uncertainty about the existence of various pericyclase classes, a series of genome mining, heterologous expression, and enzymatic activity characterization have validated a plethora of pericyclases over the past decade. The several types of pericyclases are involved in biosynthetic complexity generation of almost every major category of natural products. This text will serve as a reference point for chemists of every subdiscipline, including synthetic organic chemists and medicinal chemists. It will also be valuable to bioinformatic and computational biologists, pharmacognocists and chemical ecologists, and bioengineers and synthetic biologists.

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.

Amino Acids, Peptides and Proteins is a broad ranging title comprising comprehensive and critical reviews of significant developments at the biology and chemistry interface. Compiled by leading researchers in their subject, this volume incorporates current trends and emerging areas in topics ranging from enzymatic halogenation, unnatural amino acids in peptide and protein chemistry and detection of protein post-translational modifications by mass spectrometry. Appealing broadly to researchers in academia and industry, it will be of great benefit to any researcher wanting a succinct reference in this field and looking at the future.

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.

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.

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.

Photoaging results from chronic exposure to UV radiation and is an increasingly common clinical feature, with an aging population the clinical burden is likely to increase despite advances in our understanding of the pathology and development of improved treatments. This book will present and review the latest progress from the forefront of translational research in cutaneous photoaging. The core chapters focus on the current understanding of the biochemical mechanisms of photoageing and lead on to aspects of photoprotection and photomedicine to provide a complete picture of the current field and a context for the importance of the basic mechanistic understanding. With a global team of authors Cutaneous Photoaging provides an international perspective on the causes, consequences, pathophysiology and treatment of photoaging, ideal for dermatologists, students and professionals in photoscience.

Amino Acids, Peptides and Proteins comprises a comprehensive and critical review of significant developments at the biology and chemistry interface. Compiled by leading researchers in their subject, this volume incorporates current trends and emerging areas in topics ranging from synthetic polypeptide materials and conjugates to membrane proteins and bioactive peptides implicated in various diseases and exploited for drug design. Appealing broadly to researchers in academia and industry, it will be of great benefit to any researcher wanting a succinct reference on developments in this area now and looking to the future.

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.

Genomics and genome technology is having, and continues to have, a major impact on all areas of bioscience research providing insights into the key area of molecular mechanisms of cells in health and disease. This is causing a profound effect on biomedical science and is accelerating the development of new diagnostic applications. This book provides a timely, graduate level introduction to the fast-paced area of genomics and clinical diagnostic technologies and introduces the concept of applications based on this area. The initial chapters focus on principal molecular technologies that underpin the information in the later chapters. In addition to introductory areas of nucleic acids and techniques in molecular biology, bioinformatics and proteomics, other key diagnostic areas such as the use of immunological reagents are covered. The later chapters provide more specialised examples of currently used diagnostic technologies and insights into selected key diagnostic challenges including specific examples of molecular microbial diagnostics and molecular biomarkers in oncology. The running themes through the chapters provides an insight into current and future perspectives in this rapidly evolving field.

Kinase inhibition remains an area of significant interest, and growing importance, across academia and the pharmaceutical industry. There are now many marketed drugs that target kinases and a significant number of compounds are currently in various stages of clinical development. This book is a forward-looking analysis of a number of key areas for kinase inhibition in the coming years and builds on the first volume. This includes topics such as screening approaches to target kinases along with different modes of inhibition such as allosteric and covalent. Novel approaches such as macrocyclisation are considered along with how the properties of kinase inhibitors have evolved, including the potential for brain penetration. Recent areas of great importance also covered include cutting edge molecular modelling approaches and the importance of kinase mutations. The evolving biology of kinases has also resulted in increased interest in the immuno-oncology area and also pseudokinases as a target family. As with the first volume the book finishes with a forward looking view of how research against this fascinating target class may evolve.

Aerobic organisms have evolved to utilise the intrinsic oxidising power of oxygen from the atmosphere. This so-called'activation'of oxygen is often catalysed by a heme-containing enzyme. This book highlights the many and varied catalytic activities of O2-dependent heme–iron enzymes, including monoxygenases and cytochrome P450, dioxygenases, oxidases and model heme systems. Dioxygen-dependent Heme Enzymes will be a useful resource for postgraduate students and researchers in biochemistry and metallobiology working in, or moving into, research areas involving heme proteins.

Gas molecules such as O2, NO, CO and ethylene are present in the environment and are endogenously (enzymatically) produced to act as signalling molecules in biological systems, including the regulation of metabolic networks, chemotaxis, circadian rhythms, mammalian hypoxia responses, and plant ethylene responses by transcriptional, translational, or post translational control. Sensing these gas molecules is the first step in their acting as signalling molecules. When a sensor domain/protein senses an external signal, intra- and inter-molecular signal transductions take place to regulate the biological function of a regulatory domain/protein such as DNA-binding, enzymatic activity, or protein–protein interaction. Interaction between gas molecules and sensor proteins is essential for recognition of gas molecules. Metal-containing prosthetic groups such as haem, iron–sulfur clusters, and non-haem iron centres are widely used. As these metal-containing centres are good spectroscopic probes, detail characterizations have utilized spectroscopic techniques along with X-ray crystallography.Covering both the signalling and sensing of gaseous molecules, this book provides the first comprehensive overview of gas sensor proteins in both prokaryotic and eukaryotic cells. This book will be particularly interesting to postgraduates and researchers in biochemistry, molecular biology and metallobiology.

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.

Gasotransmitters are gas molecules produced endogenously in prokaryotic and eukaryotic cells for signalling purposes. This book provides, for the first time, a comprehensive description and systematic look at all gasotransmitters, established or proposed, since their detection in 2002. The content and scope covers the production, metabolism, and signalling roles of gasotransmitters. Conceptual advances, scientific discoveries and newly developed techniques described in this book influence our understanding of fundamental molecular and cellular events in biology and medicine. This book serves as the state-of-the-art book for undergraduate and graduate students as well as post-doctoral fellows in biomedical disciplines and toxicologists studying the toxic mechanisms of gasotransmitters in the environment. It will also be welcomed by researchers in university and research institutes, government agencies, pharmaceutical and medical instrument industry, and clinical practice.

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.

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.

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.

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.

Metal ions play key roles in biology. Many are essential for catalysis, for electron transfer and for the fixation, sensing, and metabolism of gases. Others compete with those essential metal ions or have toxic or pharmacological effects. This book is structured around the periodic table and focuses on the control of metal ions in cells. It addresses the molecular aspects of binding, transport and storage that ensure balanced levels of the essential elements. Organisms have also developed mechanisms to deal with the non-essential metal ions. However, through new uses and manufacturing processes, organisms are increasingly exposed to changing levels of both essential and non-essential ions in new chemical forms. They may not have developed defenses against some of these forms (such as nanoparticles). Many diseases such as cancer, diabetes and neurodegeneration are associated with metal ion imbalance. There may be a deficiency of the essential metals, overload of either essential or non-essential metals or perturbation of the overall natural balance. This book is the first to comprehensively survey the molecular nature of the overall natural balance of metal ions in nutrition, toxicology and pharmacology. It is written as an introduction to research for students and researchers in academia and industry and begins with a chapter by Professor R J P Williams FRS.

Authored by leading experts in the enzymology of natural product biosynthesis, this textbook provides a thorough description of the types of natural products, the biosynthetic pathways that enable the production of these molecules, and an update on the discovery of novel products in the post-genomic era. Although some 500-600,000 natural products have been isolated and characterized over the past two centuries, there may be a 10-fold greater inventory awaiting immediate exploration based on biosynthetic gene cluster predictions. The approach of this book is to codify the chemical logic that underlies each natural product structural class as they are assembled from building blocks of primary metabolism. This text will serve as a reference point for chemists of every subdiscipline, including synthetic organic chemists and medicinal chemists. It will also be valuable to bioinformatic and computational biologists, to pharmacognocists and chemical ecologists, to bioengineers and synthetic biologists.

Amino Acids, Peptides and Proteins comprises a comprehensive and critical review of significant developments at the biology and chemistry interface. Compiled by leading researchers in their subject, this volume incorporates current trends and emerging areas in topics such as magnetic resonance studies of membrane active peptides, proteins and peptides for the diagnosis and therapy of Leishmania donovani parasite infections and advances in the design of ligands interacting with proteases causing infectious respiratory syndrome. Appealing broadly to researchers in academia and industry, it will be of great benefit to any researcher wanting a succinct reference on developments in this area now and looking to the future.

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.

For human health, leishmaniasis is among the most important protozoan diseases, superseded only by malaria. Globally, 10 to 12 million people are infected with 1.5 million new cases every year. The development of cheaper new drugs is urgently needed for this neglected disease that is developing resistance to current treatments. Chemotherapy remains the only treatment option for the bulk of patients. However, this is largely unaffordable for most. In the past three years numerous advances in drug discovery have been made for treating this disease by exploiting diverging metabolic pathways between the Leishmania enzymes and their hosts, using nanotechnology to target the immune cell phagolysosomes where Leishmania resides. Drug Discovery for Leishmaniasis aims to provide a perspective of the current treatments and their challenges, blended with the emerging strategies and methodologies that will drive new target appraisals and drug developments, as well as addressing the molecular basis of resistance in Leishmania. Recent studies have shown that leishmaniasis affects some of the poorest people in the world, with 95% of fatal cases occurring in only 6 countries. With the WHO goal of eliminating this public health problem in the South-east Asia Region by 2020, this book will be important for anyone who is interested in neglected tropical diseases.

Understanding and quantifying the effects of membrane transporters within the human body is essential for modulating drug safety and drug efficacy. The first volume comprehensively reviewed current knowledge and techniques in the transporter sciences and their relations to drug metabolism and pharmacokinetics. In this second volume on Drug Transporters, emphasis is placed on emerging sciences and technologies, highlighting potential areas for future advances within the drug transporter field. The topics covered in both volumes ensure that all relevant aspects of transporters are described across the drug development process, from in silico models and preclinical tools through to the potential impact of transporters in the clinic. Contributions are included from expert leaders in the field, at-the-bench industrial scientists, renowned academics and international regulators. Case studies and emerging developments are highlighted, together with the merits and limitations of the available methods and tools, and extensive references to reviews on specific in-depth topics are also included for those wishing to pursue their knowledge further. As such, this text serves as an essential handbook of information for postgraduate students, academics, industrial scientists and regulators who wish to understand the role of transporters in absorption, distribution, metabolism, and excretion processes. In addition, it is also a useful reference tool on the models and calculations necessary to predict their effect on human pharmacokinetics and pharmacodynamics.

Understanding and quantifying the effects of membrane transporters within the human body is essential for modulating drug safety and drug efficacy. In this first volume on Drug Transporters, the current knowledge and techniques in the transporter sciences and their relations to drug metabolism and pharmacokinetics are comprehensively reviewed. The second volume of the book is specifically dedicated to emerging science and technologies, highlighting potential areas for future advances within the drug transporter field. The topics covered in both volumes ensure that all relevant aspects of transporters are described across the drug development process, from in silico models and preclinical tools through to the potential impact of transporters in the clinic. Contributions are included from expert leaders in the field, at-the-bench industrial scientists, renowned academics and international regulators. Case studies and emerging developments are highlighted, together with the merits and limitations of the available methods and tools, and extensive references to reviews on specific in-depth topics are also included for those wishing to pursue their knowledge further. As such, this text serves as an essential handbook of information for postgraduate students, academics, industrial scientists and regulators who wish to understand the role of transporters in absorption, distribution, metabolism, and excretion processes. In addition, it is also a useful reference tool on the models and calculations necessary to predict their effect on human pharmacokinetics and pharmacodynamics.

Amino Acids, Peptides and Proteins comprises a comprehensive and critical review of significant developments at the biology/chemistry interface. Compiled by leading researchers in their subject, this volume incorporates current trends and emerging areas for example new bioconjugates of metal complexes with peptides and derivatization of peptides for improved detection by mass spectrometry. Appealing broadly to researchers in academia and industry, it will be of great benefit to any researcher wanting a succinct reference to developments now and looking to the future.