Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

Klotho is the latest edition of a series first published in 1943 on Vitamins and Hormones and the longest-running serial published by Academic Press. It provides up-to-date information on vitamin and hormone research spanning data from molecular biology to the clinic, with volumes focusing on a single molecule or on a disease that is related to vitamins or hormones that are interpreted broadly so that related substances, such as transmitters, cytokines, growth factors, and others can be reviewed.

This thesis offers readers a comprehensive introduction to amyloid proteins and the computational methods used with them. Katrine Skeby critically assesses and compares both the literature and the experiments performed by other researchers, which further elevates the quality and relevance of her own work. Amyloid proteins are highly complex, and this research provides unparalleled insights, especially with regard to the origin of cytotoxicity and to developing technologies for early detection, revealing in detail the molecular mechanisms behind hIAPP behavior. Several studies within the thesis answer difficult questions which promote future research into the properties of amyloid proteins.

This volume provides a sound basis for the molecular investigation of NLR function in health and disease. Chapters focus on of innate immune receptors, "atypical" inflammasomes, biochemical and novel bioluminescence techniques for the measurement of IL-1b, bioluminescent probe, biochemical and microscopy techniques, techniques to measure caspase-1 activation, cell free systems for the study of inflammasome function, and inflammasome activation. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, NLR Proteins: Methods and Protocols aims to ensure successful results in the further study of this vital field.

This snapshot volume is designed to provide a smooth entry into the field of protein folding. Presented in a concise manner, each section introduces key concepts while providing a brief overview of the relevant literature. Outlook subsections will pinpoint specific aspects related to emerging methodologies, concepts and trends.

This volume focuses on various aspects of interleukin-27 (IL-27), especially its potential for clinical applications. The authors discuss the downstream signaling from the IL-27 receptor and its molecular targets in immune cells including Th1, Th2, Th17, Treg, Tr1, Tfh, B cells, DCs and macrophages. The inhibition of Th17 cells by IL-27 is vital for the maintenance of the feto-maternal tolerance and the prevention of lupus, multiple sclerosis, autoimmune uveitis, immune thrombocytopenia and atherosclerosis. However, the same inhibitory capabilities compromise the immune response to bacterial pathogens, and IL-27 is a pathogenic factor in sepsis and tuberculosis. Also covered are the conflicting reports on the role of IL-27 in rheumatoid arthritis, the effect of IL-27 on epithelia, which seems to play a role in asthma, psoriasis and inflammatory bowel diseases, and the direct cytotoxic and anti-vascular effects of IL-27, which make it a promising agent for the treatment of cancer. Accordingly, this volume will be of interest to researchers and clinicians alike.

This book presents advanced expression technologies for the production of protein complexes. Since complexes lie at the heart of modern biology, the expression, purification, and characterization of large amounts of high-quality protein complexes is crucial for the fields of biomedicine, biotechnology, and structural biology. From co-expression in E. coli, yeast, mammalian and insect cells to complex reconstitution from individual subunits, this book offers useful insights and guidance for successful protein expressionists. Across several sections readers will discover existing opportunities for the production of protein complexes in bacterial systems (including membrane proteins and cell-free co-expression), methylotrophic and non-methylotrophic yeasts, protozoa (Leishmania terantolae and Dictyostelium discoideum), baculovirus-infected insect cells, mammalian cells, plants and algae. Complex reconstitution from individually purified subunits or subcomplexes is discussed as a complementary strategy. A last section introduces briefly some of the biophysical and structural characterization techniques for macromolecular complexes using state-of-the-art solution scattering and nuclear magnetic resonance. This work is a guided tour over some of the most powerful and successful protein expression technologies, with a focus on co-expression and high-throughput applications. It is addressed to everyone interested in the production and characterization of macromolecular complexes, from university students who want an accessible description of the major co-expression systems to researchers in biomedicine and the life sciences seeking for an up-to-date survey of available technologies.

This book offers an overview of our current understanding of host defense peptides and their potential for clinical applications as well as some of the obstacles to this. The chapters, written by leading experts in the field, detail the number and diversity of host defense peptides, and discuss the therapeutic potential not only of antibacterial, but also of antifungal, antiviral, plant antimicrobial and anticancer host defense peptides. The authors provide new insights into their mechanisms of action and their immunomodulatory properties, and review recent advances in the design of novel therapeutic molecules. Lastly, their potential to prevent preterm births and Staphylococcus aureus infections is highlighted. The book is of interest to researchers, industry and clinicians alike.

Now in its third edition and supplemented with more online material, this book aims to make the "new" information-based (rather than gene-based) bioinformatics intelligible both to the "bio" people and the "info" people. Books on bioinformatics have traditionally served gene-hunters, and biologists who wish to construct family trees showing tidy lines of descent. While dealing extensively with the exciting topics of gene discovery and database-searching, such books have hardly considered genomes as information channels through which multiple forms and levels of information have passed through the generations. This "new bioinformatics" contrasts with the "old" gene-based bioinformatics that so preoccupies previous texts. Forms of information that we are familiar with (mental, textual) are related to forms with which we are less familiar (hereditary). The book extends a line of evolutionary thought that leads from the nineteenth century (Darwin, Butler, Romanes, Bateson), through the twentieth (Goldschmidt, White), and into the twenty first (the final works of the late Stephen Jay Gould). Long an area of controversy, diverging views may now be reconciled.

This volume provides a collection of protocols and approaches for the creation of novel ligand binding proteins, compiled and described by many of today's leaders in the field of protein engineering. Chapters focus on modeling protein ligand binding sites, accurate modeling of protein-ligand conformational sampling, scoring of individual docked solutions, structure-based design program such as ROSETTA, protein engineering, and additional methodological approaches. Examples of applications include the design of metal-binding proteins and light-induced ligand binding proteins, the creation of binding proteins that also display catalytic activity, and the binding of larger peptide, protein, DNA and RNA ligands. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls.

Ion Channels as Therapeutic Targets is the latest volume in the popular Advances in Protein Chemistry and Structural Biology series, an essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins, with each thematically organized volume guest edited by leading experts in a broad range of protein-related topics.

This book has been conceives as a brief introduction to biomembranes physical chemistry for undergraduate students of sciences, and it is particularly dedicated to the lipid-protein membrane interactions. A general introduction is presented in Chapters 1 and 2. The following Chapters, 3 and 4, describe the most accepted theories on lipid-membrane protein interactions as well as the new experimental approaches, in particular, these arose from nano sciences as atomic for microscopy and single molecule force spectroscopy. The book emphasizes the relevance of physical parameters as the lateral surface pressure and the lipid curvature as actors for understanding the physicochemical properties of the biomembranes.

The Advances in Protein Chemistry and Structural Biology series is an essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins, with each thematically organized volume guest edited by leading experts in a broad range of protein-related topics.

This detailed volume explores the continuing techniques of studying RNA-protein complexes and interactions as research in these areas expand. After an introductory chapter, the book continues with ways to purify RNA-protein complexes assembled in cells or in isolated cellular extracts, methods for measuring various biochemical activities of RNA-interacting proteins or ribonucleoproteins, biochemical methods for measuring direct RNA-protein contact, as well as various new or innovative methods pertinent to the subject. Written for the highly successful Methods in Molecular Biology series, chapters contain brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, RNA-Protein Complexes and Interactions: Methods and Protocols provides a set of useful protocols, both basic and advanced, designed to inspire researchers working with RNA and RNA-interacting proteins.

Intermediate Filament Associated Proteins, the latest volume in the Methods in Enzymology series, continues the legacy of this premier serial with quality chapters authored by leaders in the field. This volume covers research methods in intermediate filament associated proteins and contains sections on such topics as lamin-associated proteins, intermediate filament-associated proteins and plakin, and other cytoskeletal cross-linkers.

This volume describes prominent methodologies developed by laboratories that have been leading the field of quantitative proteomics by mass spectrometry. The procedures for performing the experiments are described in an easy-to-understand manner with many technical details that usually are not reported in typical research articles. This second edition of Quantitative Proteomics by Mass Spectrometry provides a broad perspective of the methodologies used for quantifying proteins and post-translational modifications in different types of biomedical specimens. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and thorough, Quantitative Proteomics by Mass Spectrometry, Second Edition is a valuable resource to help researchers understand and learn about the latest tools used in the study of quantitative proteomics by mass spectrometry.

This volume presents an overview of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) structure and function. It then continues with methods for the analysis of these pathways including conventional enzymological assays, contemporary mass spectrometric analysis techniques, specialized molecular biological approaches applicable to NRPSs and PKSs, and small molecule analysis tools tailored to this very special class of natural products, and concludes by examining bioinformatics tools for the analysis of these enzymes, pathways, and molecules. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Nonribosomal Peptide and Polyketide Biosynthesis: Methods and Protocols serves as a valuable reference for those experienced in studying NRPS and PKS enzymes, pathways, and natural products as well as a gateway for those just entering the field.

This second edition volume expands on the first edition with new developments on Toll-Like Receptors (TLRs) controlling events such as cross-priming of associated pattern recognition receptors, post-transcriptional regulation, interaction with other cellular and biologic systems, and cancer progression. This book is divided into five sections: Part I outlines methods for TLR detection, interaction, and intracellular trafficking; Part II describes methods and assays to investigate how TLRs cross-prime other pattern recognition receptors, including intracellular DNA receptors and inflammasome formation; Part III highlights RNA regulation, detailing how TLRs can induce RNA transcripts and molecules such as lncRNAs and microRNAs; Part IV explores TLR detection and activation in systems such as epithelial barrier function, metabolism and the circadian clock, as well as cellular systems including T and B lymphocytes; and Part V describes models to delineate the role of TLRs in diseases such as dermatitis, arthritis, and gastric cancer. Written in the highly successful Methods in Molecular Biology series format, each chapter contains a summary, a list of required materials, step-by-step, readily reproducible laboratory protocols, useful notes to investigate TLRs in cell culture, systems and disease, and tips on troubleshooting and avoiding known pitfalls. Practical and cutting-edge, Toll-Like Receptors: Methods and Protocols, Second Edition is a valuable resource to any immunologist, molecular or medical biologist working in a laboratory setting. It will add skill to both students and the more advanced molecular biologist who wishes to learn a new technique or move to a different area within their current repertoire of practical knowledge.

Introduction to Protein Mass Spectrometry provides a comprehensive overview of this increasingly important, yet complex, analytical technique. Unlike many other methods which automatically yield an absolutely unique protein name as output, protein mass spectrometry generally requires a deduction of protein identity from determination of peptide fragmentation products. This book enables readers to both understand, and appreciate, how determinations about protein identity from mass spectrometric data are made. Coverage begins with the technical basics, including preparations, instruments, and spectrometric analysis of peptides and proteins, before exploring applied use in biological applications, bioinformatics, database, and software resources. Citing the most recent and relevant work in the field of biological mass spectrometry, the book is written for researchers and scientists new to the field, but is also an ideal resource for those hoping to hone their analytical abilities.

Na+-K+ ATPase or Na-pump ATPase, a member of "P"-type ATPase superfamily, is characterized by association of multiple isoforms mainly of it's - and - subunits. At present four different - ( -1, -2, -3 and -4) and three - ( -1, -2, and -3) isoforms have been identified in mammalian cells and their differential expressions are tissue specific. Regulation of Na+-K+ ATPase activity is an important but a complex process, which involves short-term and long-term mechanisms. Short-term regulation of Na+-K+ ATPase is either mediated by changes in intracellular Na+ concentrations that directly affect the Na+-pump activity or by phosphorylation/dephosphorylation-mediated by some stimulants leading to changes in its expression and transport properties. On the other hand, long-term regulation of Na+-K+ ATPase is mediated by hormones, such as mineralocorticoids and thyroid hormones, which cause changes in the transcription of genes of - and - subunits leading to an increased expression in the level of Na+-pump. Several studies have revealed a relatively new type of regulation that involves the association of small, single span membrane proteins with this enzyme. These proteins belong to the FXYD family, the members of which share a common signature sequence encompassing the transmembra ne domain adjacent to the isoform(s) of - subunits of Na+-K+ ATPase. Considering the extraordinary importance of Na+-K+ ATPase in cellular function, several internationally established investigators have contributed their articles in the monograph entitled "Regulation of Membrane Na+-K+ ATPase" for inspiring young scientists and graduate students to enrich their knowledge on the enzyme, and we are sure that this book will soon be considered as a comprehensive scientific literature in the area of Na+-K+ ATPase regulation in health and disease.

This book is a passionate account of the scientific breakthroughs that led to the solution of the first protein structures and to the understanding of their function at atomic resolution. The book is divided into self-standing chapters that each deal with a protein or protein family. The subject is presented in a fluid, non-technical style that will engage student and scientists in biochemistry, biophysics, molecular and structure biology and physiology.

The biological membranes of cellular organization enfold an important group of membrane proteins called the ATPases, which are not only versatile in maintaining chemical gradient and electrical potential across the membrane but also bring metabolites necessary for cell metabolism and drive out toxins, waste products and solutes that otherwise can curb cell functions. ATPases are distributed virtually in all live forms starting from unicellular to multicellular and also in viruses. There are different types of ATPases, which differ in function and structure and in the type of ions they transport. The three main types of the ion pump ATPase family are: (i) P-type ATPases that transport different ions across membranes and Ca2+ATPases belongs to this catagory (ii) F-type ATPase in mitochondria, chloroplasts and bacterial plasma membranes produce ATP using the proton gradient; and (iii) V-type ATPase catalyzes ATP hydrolysis to transport solutes and maintains acidic pH in organelles like lysosomes. Genetic defects in either of the ATPases cause several diseases and a number of researches have demonstrated the involvement of the members of ATPases in the cell pathology and diseases, thereby penetrating exciting new areas of our understanding. In this book, the authors summarize recent knowledge about the molecular mechanisms associated with Ca2+-ATPase, V-ATPase and F-ATPase in intracellular and extracellular Ca2+ transport, mitochondrial ATP synthase, vesicular H+ transport, and lysosomal pH regulation. This book thereby bridges the gap between fundamental research and biomedical and pharmaceutical applications. The book provides an informative resource to improve ATPase research and modern therapeutic approaches toward different life threatening diseases that are associated with dysregulation of the ATPases.

The Advances in Protein Chemistry and Structural Biology series is an essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins, with each thematically organized volume guest edited by leading experts in a broad range of protein-related topics.

This volume provides up-to-date scientific achievements from the world's top researchers. Recombinant Proteins from Plants: Methods and Protocols, Second Edition guides readers through protocolsfor use with a variety of plant expression systems. Various aspects of production are covered including vector selection and cloning; product improvements for stability, glycosylation, and antibiotic-free selection; extraction and scale-up; and analysis of transgenic plants and their recombinant proteins. Written for the Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Recombinant Proteins from Plants: Methods and Protocols, Second Edition is an ideal reference for those who are interested in plant molecular biology and molecular farming.

Exploring the 2-D gel mapping field, the chapters in this book are separated into four different categories: Part I talks about 2-D maps reproducibility and maps modeling; Part II describes the image analysis tools that provide spot volume datasets; Part III is about the statistical methods applied to spot volume datasets to identify candidate biomarkers; and Part IV discusses differential analysis from direct image analysis tools. 2-D PAGE Map Analysis: Methods and Protocols provides a unique approach to 2-D gel mapping, in that it helps users avoid drawbacks due to ignorance of the basic theoretical mechanisms underlying the technique, including data handling and proper tools for spot analysis. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, 2-D PAGE Map Analysis: Methods and Protocols, is a useful resource for any scientist or researcher, with a mathematical background, who is interested in 2-D gel mapping.