Peptides are a rapidly growing class of mediators whose activity regulates homeostasis as well as pathological processes. Most of the peptide-activated receptors belong to the superfamily of 7 transmembrane domain receptors coupled to G proteins. Peptides of different sizes (from a few to more than 100 aminoacids) activate peptidergic receptors by interacting at specific sites, that often differ from those where antagonists bind. Other receptors are activated by proteases that, by cleaving the receptor extracellular region, unmask a tethered ligand. G protein-coupled receptors for chemokines represent the way of entry of the HIV virus in target cells. The great impact of non peptide agonist/antagonists in current and future medicine reflects these large variety of functions and modes of activation of peptidergic G protein-coupled receptors.
With potentially high specificity and low toxicity, biologicals offer promising alternatives to small-molecule drugs. Peptide therapeutics have again become the focus of innovative drug development efforts backed up by a resurgence of venture funds and small biotechnology companies. What does it take to develop a peptide-based medicine? What are the key challenges and how are they overcome? What are emerging therapeutics for peptide modalities? This book answers these questions with a holistic story from molecules to medicine, combining the themes of design, synthesis and clinical applications of peptide-based therapeutics and biomarkers. Chapters are written and edited by leaders in the field from industry and academia and they cover the pharmacokinetics of peptide therapeutics, attributes necessary for commercially successful metabolic peptides, medicinal chemistry strategies for the design of peptidase-resistant peptide analogues, disease classes for which peptide therapeutic are most relevant, and regulatory issues and guidelines. The critical themes covered provide essential background information on what it takes to develop peptide-based medicine from a chemistry perspective and views on the future of peptide drugs. This book will be a valuable resource not only as a reference book for the researcher engaged in academic and pharmaceutical setting, from basic research to manufacturing and from organic chemistry to biotechnology, but also a valuable resource to graduate students to understand discovery and development process for peptide-based medicine.
The need to continually discover new agents for the control or treatment of invertebrate pests and pathogens is undeniable. Agriculture, both animal and plant, succeeds only to the extent that arthropod and helminth consumers, vectors and pathogens can be kept at bay. Humans and their companion animals are also plagued by invertebrate parasites. The deployment of chemical agents for these purposes inevitably elicits the selection of resistant populations of the targets of control, necessitating a regular introduction of new kinds of molecules. Experience in other areas of chemotherapy has shown that a thorough understanding of the biology of disease is an essential platform upon which to build a discovery program. Unfortunately, investment of research resources into understanding the basic physiology of invertebrates as a strategy to illuminate new molecular targets for pesticide and parasiticide discovery has been scarce, and the pace of introduction of new molecules for these indications has been slowed as a result. An exciting and so far unexploited area to explore in this regard is invertebrate neuropeptide physiology. This book was assembled to focus attention on this promising field by compiling a comprehensive review of recent research on neuropeptides in arthropods and helminths, with contributions from many of the leading laboratories working on these systems.
G protein-coupled receptors (GPCRs) are one of the most important target classes in pharmacology and are the target of many blockbuster drugs. Yet only with the recent elucidation of the rhodopsin structure have these receptors become amenable to a rational drug design. Based on recent examples from academia and the pharmaceutical industry, this book demonstrates how to apply the whole range of bioinformatics, chemoinformatics and molecular modeling tools to the rational design of novel drugs targeting GPCRs. Essential reading for medicinal chemists and drug designers working with this largest class of drug targets in the human genome.
Since the first TRP ion channel was discovered in Drosophila melanogaster in 1989, the progress made in this area of signaling research has yielded findings that offer the potential to dramatically impact human health and wellness. Involved in gateway activity for all five of our senses, TRP channels have been shown to respond to a wide range of st
An understanding of the nervous system at virtually any level of analysis requires an understanding of its basic building block, the neuron. From Molecules to Networks provides the solid foundation of the morphologic, biochemical, and biophysical properties of nerve cells. All chapters have been thoroughly revised for this second edition to reflect the significant advances of the past 5 years. The new edition expands on the network aspects of cellular neurobiology by adding a new chapter, Information Processing in Neural Networks, and on the relation of cell biological processes to various neurological diseases. The new concluding chapter illustrates how the great strides in understanding the biochemical and biophysical properties of nerve cells have led to fundamental insights into important aspects of neurodegenerative disease. - Written and edited by leading experts in the field, the second edition completely and comprehensively updates all chapters of this unique textbook - Discusses emerging new understanding of non-classical molecules that affect neuronal signaling - Full colour, professional graphics throughout - Includes two new chapters: Information Processing in Neural Networks - describes the principles of operation of neural networks and the key circuit motifs that are common to many networks in the nervous system. Molecular and Cellular Mechanisms of Neurodegenerative Disease - introduces the progress made in the last 20 years in elucidating the cellular and molecular mechanisms underlying brain disorders, including Amyotrophic Lateral Sclerosis (ALS), Parkinson disease, and Alzheimer's disease
These conference papers review the current state of research in the field of neuropeptides and peptergic neurons. Special topics concern molecular aspects of processing, release and degradation of neuropeptides, receptors and signal transduction, and comparative and behavioural aspects.
Invertebrates have proven to be extremely useful model systems for gaining insights into the neural and molecular mechanisms of sensory processing, motor control and higher functions such as feeding behavior, learning and memory, navigation, and social behavior. A major factor in their enormous contributions to neuroscience is the relative simplicity of invertebrate nervous systems. In addition, some invertebrates, primarily the molluscs, have large cells, which allow analyses to take place at the level of individually identified neurons. Individual neurons can be surgically removed and assayed for expression of membrane channels, levels of second messengers, protein phosphorylation, and RNA and protein synthesis. Moreover, peptides and nucleotides can be injected into individual neurons. Other invertebrate model systems such as Drosophila and Caenorhabditis elegans offer tremendous advantages for obtaining insights into the neuronal bases of behavior through the application of genetic approaches. The Oxford Handbook of Invertebrate Neurobiology reviews the many neurobiological principles that have emerged from invertebrate analyses, such as motor pattern generation, mechanisms of synaptic transmission, and learning and memory. It also covers general features of the neurobiology of invertebrate circadian rhythms, development, and regeneration and reproduction. Some neurobiological phenomena are species-specific and diverse, especially in the domain of the neuronal control of locomotion and camouflage. Thus, separate chapters are provided on the control of swimming in annelids, crustaea and molluscs, locomotion in hexapods, and camouflage in cephalopods. Unique features of the handbook include chapters that review social behavior and intentionality in invertebrates. A chapter is devoted to summarizing past contributions of invertebrates to the understanding of nervous systems and identifying areas for future studies that will continue to advance that understanding.
Pituitary Adenylate Cyclase-Activating Polypeptide is the first volume to be written on the neuropeptide PACAP. It covers all domains of PACAP from molecular and cellular aspects to physiological activities and promises for new therapeutic strategies. Pituitary Adenylate Cyclase-Activating Polypeptide is the twentieth volume published in the Endocrine Updates book series under the Series Editorship of Shlomo Melmed, MD.
