Download or read book Protein Homeostasis in Drug Discovery written by Milka Kostic and published by John Wiley & Sons. This book was released on 2022-11-15 with total page 564 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein Homeostasis in Drug Discovery Comprehensive resource on all aspects of protein homeostasis, covering both historical perspectives and emerging technologies that are revolutionizing the field Protein Homeostasis in Drug Discovery highlights drug discovery and development efforts targeting protein homeostasis and considers the emerging appreciation that a protein’s activity may not be the only factor to consider when developing therapeutic agents. The chapters cover various aspects of protein homeostasis such as cellular localization, abundance, interactions, and more. Moreover, the text contains up-to-date information regarding targeted protein degradation, an emerging drug discovery modality. Readers interested in targeting different regulatory events that control protein homeostasis or modulating protein abundance will find this book an excellent resource. Furthermore, those interested in the link between biological function and regulating protein levels in living organisms, especially in the context of drug discovery, will learn from numerous examples discussed in this book. In Protein Homeostasis in Drug Discovery, readers can expect to find information on: Protein folding, quality control, pharmacology, and drug targeting processes Recent advances in our understanding of protein homeostasis, covering emerging technologies and opportunities for therapeutic intervention Targeted protein degradation (TPD) and strategies such as PROTACs and molecular glues, including a chapter on TPD as an antiviral drug discovery strategy Drug discovery and development efforts aimed at correcting, stabilizing, and rescuing proteins, with examples included Advantages and key shortcomings of both phenotypic and target-based traditional drug discovery methods Collectively, Protein Homeostasis in Drug Discovery offers the reader an opportunity to learn more about the importance of considering and targeting protein homeostasis. The text is a must-read resource for academics, professionals in the pharmaceutical industry, and advanced students in various science-related fields.
Download or read book Protein Homeostasis Diseases written by Angel L. Pey and published by Academic Press. This book was released on 2020-02-13 with total page 452 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein Homeostasis Diseases: Mechanisms and Novel Therapies offers an interdisciplinary examination of the fundamental aspects, biochemistry and molecular biology of protein homeostasis disease, including the use of natural and pharmacological small molecules to treat common and rare protein homeostasis disorders. Contributions from international experts discuss the biochemical and genetic components of protein homeostasis disorders, the mechanisms by which genetic variants may cause loss-of-function and gain-of-toxic-function, and how natural ligands can restore protein function and homeostasis in genetic diseases. Applied chapters provide guidance on employing high throughput sequencing and screening methodologies to develop pharmacological chaperones and repurpose approved drugs to treat protein homeostasis disorders. - Provides an interdisciplinary examination of protein homeostasis disorders, with an emphasis on treatment strategies employing small natural and pharmacological ligands - Offers applied approaches in employing high throughput sequencing and screening to develop pharmacological chaperones to treat protein homeostasis disease - Gathers expertise from a range of international chapter authors who work across various biological methods and disease specific disciplines of relevance
Download or read book Protein Degradation with New Chemical Modalities written by Craig Crews and published by Royal Society of Chemistry. This book was released on 2020-10-08 with total page 382 pages. Available in PDF, EPUB and Kindle. Book excerpt: Targeting protein degradation using small molecules is one of the most exciting small-molecule therapeutic strategies in decades and a rapidly growing area of research. In particular, the development of proteolysis targeting chimera (PROTACs) as potential drugs capable of recruiting target proteins to the cellular quality control machinery for elimination has opened new avenues to address traditionally 'difficult to target' proteins. This book provides a comprehensive overview from the leading academic and industrial experts on recent developments, scope and limitations in this dynamically growing research area; an ideal reference work for researchers in drug discovery and chemical biology as well as advanced students.
Download or read book Protein Homeostasis in Drug Discovery written by Milka Kostic and published by John Wiley & Sons. This book was released on 2022-12-01 with total page 564 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein Homeostasis in Drug Discovery Comprehensive resource on all aspects of protein homeostasis, covering both historical perspectives and emerging technologies that are revolutionizing the field Protein Homeostasis in Drug Discovery highlights drug discovery and development efforts targeting protein homeostasis and considers the emerging appreciation that a protein’s activity may not be the only factor to consider when developing therapeutic agents. The chapters cover various aspects of protein homeostasis such as cellular localization, abundance, interactions, and more. Moreover, the text contains up-to-date information regarding targeted protein degradation, an emerging drug discovery modality. Readers interested in targeting different regulatory events that control protein homeostasis or modulating protein abundance will find this book an excellent resource. Furthermore, those interested in the link between biological function and regulating protein levels in living organisms, especially in the context of drug discovery, will learn from numerous examples discussed in this book. In Protein Homeostasis in Drug Discovery, readers can expect to find information on: Protein folding, quality control, pharmacology, and drug targeting processes Recent advances in our understanding of protein homeostasis, covering emerging technologies and opportunities for therapeutic intervention Targeted protein degradation (TPD) and strategies such as PROTACs and molecular glues, including a chapter on TPD as an antiviral drug discovery strategy Drug discovery and development efforts aimed at correcting, stabilizing, and rescuing proteins, with examples included Advantages and key shortcomings of both phenotypic and target-based traditional drug discovery methods Collectively, Protein Homeostasis in Drug Discovery offers the reader an opportunity to learn more about the importance of considering and targeting protein homeostasis. The text is a must-read resource for academics, professionals in the pharmaceutical industry, and advanced students in various science-related fields.
Download or read book The Networking of Chaperones by Co chaperones written by Gregory Lloyd Blatch and published by Springer. This book was released on 2014-12-08 with total page 286 pages. Available in PDF, EPUB and Kindle. Book excerpt: Co-chaperones are important mediators of the outcome of chaperone assisted protein homeostasis, which is a dynamic balance between the integrated processes of protein folding, degradation and translocation. The Networking of Chaperones by Co-chaperones describes how the function of the major molecular chaperones is regulated by a cohort of diverse non-client proteins, known as co-chaperones. The second edition includes the current status of the field and descriptions of a number of novel co-chaperones that have been recently identified. This new edition has a strong focus on the role of co-chaperones in human disease and as putative drug targets. The book will be a resource for both newcomers and established researchers in the field of cell stress and chaperones, as well as those interested in cross-cutting disciplines such as cellular networks and systems biology.
Download or read book Protein Homeostasis in Growth Development and Disease written by Francesco Fazi and published by Frontiers Media SA. This book was released on 2023-03-08 with total page 136 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Protein Tyrosine Phosphatases written by Lalima G. Ahuja and published by de Gruyter. This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Reversible protein phosphorylation is one of the key mechanisms for cell signaling. Protein Tyrosine Kinases serve as the 'signaling currency' of the cell, while Protein Tyrosine Phosphatases (PTPs) ensure homeostasis, which is critical to cell surv
Download or read book The Discovery and Characterization of Small Molecule 20s Proteasome Activators written by Evert Njomen and published by . This book was released on 2019 with total page 205 pages. Available in PDF, EPUB and Kindle. Book excerpt: Maintenance of proteome fidelity is required to preserve the health of an organism in defiance of developmental fluxes, environmental insults, infectious diseases, and the challenges of aging. This crucial role is the responsibility of the proteostasis (protein homeostasis) network, a multicomponent and unified system involving protein synthesis, folding, and degradation. The degradation system is regulated by the proteasome and the autophagy pathways. These proteolytic systems have thus emerged as therapeutic targets for numerous proteostasis disorders. However, their therapeutic regulation is only feasible if there is a fine understanding of how they function, and the mechanisms of crosstalk underlying their cooperative nature. After more than three decades since the discovery of the proteasome, there is still so much to be known about this exquisite enzyme. Proteolysis by the proteasome could be 20S- or 26S-mediated and may or may not be ubiquitin-dependent. The goal of this dissertation was to discover and characterize small molecules that allow for the decoding of 20S-mediated proteolysis and its role in the regulation of autophagy, with the hope of finding new vulnerabilities for proteostasis drug discovery.In this endeavor, two classes of 20S proteasome activators; imidazolines and phenothiazines were identified via high throughput screening (HTS). In a mechanistic study consisting of cellular, biochemical, biophysical and computational approaches, the imidazoline, TCH-165, was found to stabilize the open-gate active conformation of the human 20S proteasome. This translated into enhanced degradation of cancer-driving intrinsically disordered proteins (IDPs) such as c-Myc, and sensitization of both established and primary cancer cells to this molecule. TCH-165 was also found to enhance 20S-mediated clearance of two key SNARE proteins; SNAP29 and STX17, with subsequent inhibition of autolysosome formation. These observations implicate the 20S proteasome as a key regulator of autophagic flux. The clearance of ubiquitinylated proteins was not affected at concentrations required to boost 20S-mediated degradation of these IDPs. Thus, the 20S-ubiquitin-independent pathway could be enhanced without significantly affecting the 26S-ubiquitin-dependent pathway. These findings provide a new targetable vulnerability for IDP-driven cancers and autophagy-associated chemoresistance.In a proof-of-concept approach, the phenothiazine, chlorpromazine was modified to diminish its dopamine D2 receptor (D2R) activity while retaining its ability to enhance 20S-mediated proteolysis of IDPs associated with neurodegenerative disorders. Using these molecules as controls, the AlphaLISA technology was applied in a proteasome-protein degradation system thereby allowing for the development of an assay that allows for the measurement of 20S activation at the cellular and protein levels. These small molecule 20S agonists can therefore serve as leads to further explore the therapeutic potential of 20S activation in proteostasis disorders or as new tools to provide insight into the ambiguous mechanics of 20S-gate regulation and signaling.In an expanded exploration to cover infectious diseases, some imidazolines were found to inhibit the growth of Mycobacterium tuberculosis (Mtb), the causative agent for tuberculosis (TB). Given the structural differences between human and Mtb proteasome, CRISPRi/dCas9 system was used to validate the Mtb proteasome as a target for this anti-mycobacterium activity.
Download or read book Protein Homeostasis written by Richard I. Morimoto and published by . This book was released on 2012 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proper folding of proteins is crucial for cell function. Chaperones and enzymes that post-translationally modify newly synthesized proteins help ensure that proteins fold correctly, and the unfolded protein response functions as a homeostatic mechanism that removes misfolded proteins when cells are stressed. This book covers the entire spectrum of proteostasis in healthy cells and the diseases that result when control of protein production, protein folding, and protein degradation goes awry.
Download or read book Inducing Targeted Protein Degradation written by Philipp Cromm and published by John Wiley & Sons. This book was released on 2022-11-15 with total page 389 pages. Available in PDF, EPUB and Kindle. Book excerpt: Inducing Targeted Protein Degradation Enables drug developers in academia and industry to expand the range of accessible drug targets through induced protein degradation Since the breakthrough of the PROTAC technology in 2015, targeted protein degradation has revolutionized drug discovery, enabling pharma companies to develop completely novel therapeutics. Inducing Targeted Protein Degradation is a timely guide to navigating the complexities of the subject and understanding its practical application, with an eye on expanding the druggable space. In Inducing Targeted Protein Degradation, readers will find the most recent information on: Cellular mechanisms of targeted protein degradation and current approaches to utilize these mechanisms for drug discovery A comparison of different induced degradation approaches, including PROTAC, molecular glues, LYTACs and ATTECs as well as additional post translational modifications Drug development aspects such as DMPK optimization and criteria for the selection of clinical candidates A discussion of the potential of targeted degradation for expanding the druggable space Inducing Targeted Protein Degradation will serve as a practice-oriented reference on induced protein degradation for drug discovery professionals and for researchers employing chemical biology approaches.
Download or read book Membrane Transporters and Channels as Targets for Drugs written by Graça Soveral and published by Frontiers Media SA. This book was released on 2020-01-03 with total page 333 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transporters and channels are membrane proteins that mediate the traffic of metabolites, water and ions across biological membranes. Membrane transport proteins are crucial to maintain homeostasis and assure cell survival upon intracellular or environmental stress. A failure of any of these transport systems may have dramatic consequences for cell function. There is increasing evidence that membrane transport proteins play important functions in healthy conditions and that their absence or dysfunction may cause diseases. In recent years much attention has been paid to diseases resulting from defective transporters (“carrier diseases”) and ion channels (“channelopathies”). Very interestingly, altered expression of transporters has been described in several human pathologies. On this basis, many transport proteins are well acknowledged targets for drugs. Many others are involved in drug delivery and disposition and/or are considered potential targets. Others are off-targets for drugs and then, are responsible for side effects. Thus, membrane protein drug discovery is now an emerging field where the search for physiological mechanisms of regulation and for chemical compounds as modulators of transport activity, present new opportunities for drug development and for new therapies. This Research Topic addresses the latest research advances in membrane transport proteins, stimulating future research on these important protein families.
Download or read book Molecular Evolutionary Models in Drug Discovery written by Juan Bueno and published by Academic Press. This book was released on 2020-01-22 with total page 194 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular Evolutionary Models in Drug Discovery explores the application of evolutionary molecular models in drug discovery in which secondary metabolites play a fundamental role. Secondary metabolites are not produced in isolation, they are the result of the interaction of genes, metabolism and the environment. The book examines the role of secondary metabolites as leads in drug discovery and on the development of a rational bioprospecting model for new medicines based on the evolution of secondary metabolism. These evolutionary models are part of biological systems and are the most reliable expression of the functioning of living beings. - Examines the integration and application of evolutionary models in the pharmaceutical industry to create new drug development platforms - Investigates the biotechnological prospecting of secondary metabolites and their potential use in the discovery of new drugs - Evaluates the ecosystem of living beings and how its molecular adaptation might improve the success of therapies
Download or read book Functional Proteomics written by Luke Erber and published by American Chemical Society. This book was released on 2021-12-30 with total page 161 pages. Available in PDF, EPUB and Kindle. Book excerpt: The fundamental importance of proteins in cellular activity and drug discovery combined with the enormous complexity of proteoforms requires wide-ranging strategies to characterize the proteome at a system-wide scale. Because of its speed, sensitivity, and reliability, mass spectrometry–based proteomics technology has become a critical platform for systematic analysis of proteins. Functional Proteomics covers the basic knowledge about and summarizes some of the latest developments in this field as an introduction for anyone interested in applying functional proteomics strategies to study biological pathways and diseases.
Download or read book Protein Allostery in Drug Discovery written by Jian Zhang and published by Springer Nature. This book was released on 2019-11-09 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book focuses on protein allostery in drug discovery. Allosteric regulation, ʹthe second secret of lifeʹ, fine-tunes virtually most biological processes and controls physiological activities. Allostery can both cause human diseases and contribute to development of new therapeutics. Allosteric drugs exhibit unparalleled advantages compared to conventional orthosteric drugs, rendering the development of allosteric modulators as an appealing strategy to improve selectivity and pharmacodynamic properties in drug leads. The Series delineates the immense significance of protein allostery—as demonstrated by recent advances in the repertoires of the concept, its mechanistic mechanisms, and networks, characteristics of allosteric proteins, modulators, and sites, development of computational and experimental methods to predict allosteric sites, small-molecule allosteric modulators of protein kinases and G-protein coupled receptors, engineering allostery, and the underlying role of allostery in precise medicine. Comprehensive understanding of protein allostery is expected to guide the rational design of allosteric drugs for the treatment of human diseases. The book would be useful for scientists and students in the field of protein science and Pharmacology etc.
Download or read book Chemical Proteomics written by Gerard Drewes and published by Humana Press. This book was released on 2011-11-08 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The multidisciplinary science of chemical proteomics studies how small molecules of synthetic or natural origin bind to proteins and modulate their function. In Chemical Proteomics: Methods and Protocols, expert researchers in the field provide key techniques to investigate chemical proteomics focusing on analytical strategies, how probes are generated, techniques for the discovery of small molecule targets and the probing of target function, and small molecule ligand and drug discovery. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Chemical Proteomics : Methods and Protocols seeks to provide methodologies that will contribute to a wider application of chemical proteomics methods in biochemical and cell biological laboratories.
Download or read book Neurodegeneration written by Danilo Milardi and published by Royal Society of Chemistry. This book was released on 2011-06-24 with total page 285 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since Alois Alzheimer described the results of his postmortem studies in 1906, significant strides have been made in understanding the pathogenesis of neurodegenerative diseases. Substantial evidence has accumulated indicating that diverse neurodegenerative disorders might share a common pathological mechanism: the misfolding, aggregation and accumulation of proteins (termed "amyloid") in the brain. Metal ions have long been thought to catalyze protein misfolding initiating a cascade of events resulting in oxidative damage and neurodegeneration. They have, consequently, been seen as a suitable pharmacological target. However, drugs aimed at simply removing excess metals or interfering in amyloid deposition were unsuccessful and scientists have been forced to review the classical hypothesis. The latest advances suggest that deficiencies in protein homeostasis may lead to cell dysfunction and disease. Furthermore, small molecules with the potential to control metal homeostasis, or metallostasis, are expected to provide the framework for the design of novel proteostasis regulators. This book provides an up-date on the latest developments in this fast moving field. Traditional views concerning the relationship between the physio-pathological cycles of copper, zinc, iron, aluminium and the evolution of life, are compared with emerging ideas in the neuroscience of metal ions. Topics covered emphasize the importance of metals and oxidation chemistry to neuroscientists as well as providing a wider, multidisciplinary background to chemists who are attracted by these fascinating subjects. The text starts with a chapter on chemical evolution, the brain and metallomics which describes the brain's natural defences to adverse conditions. It then goes on to cover the chemistry and biology of proteostasis, environmental factors, and the role played by membranes in protein misfolding. The remaining chapters cover the role of metals and oxidative stress in Alzheimer's Disease, Parkinsonism, ALS and other neurodegenerative diseases. The book is suitable for academics, those working in industry, and postgraduate students.
Download or read book Mass Spectrometry Based Chemical Proteomics written by W. Andy Tao and published by John Wiley & Sons. This book was released on 2019-07-10 with total page 448 pages. Available in PDF, EPUB and Kindle. Book excerpt: PROVIDES STRATEGIES AND CONCEPTS FOR UNDERSTANDING CHEMICAL PROTEOMICS, AND ANALYZING PROTEIN FUNCTIONS, MODIFICATIONS, AND INTERACTIONS—EMPHASIZING MASS SPECTROMETRY THROUGHOUT Covering mass spectrometry for chemical proteomics, this book helps readers understand analytical strategies behind protein functions, their modifications and interactions, and applications in drug discovery. It provides a basic overview and presents concepts in chemical proteomics through three angles: Strategies, Technical Advances, and Applications. Chapters cover those many technical advances and applications in drug discovery, from target identification to validation and potential treatments. The first section of Mass Spectrometry-Based Chemical Proteomics starts by reviewing basic methods and recent advances in mass spectrometry for proteomics, including shotgun proteomics, quantitative proteomics, and data analyses. The next section covers a variety of techniques and strategies coupling chemical probes to MS-based proteomics to provide functional insights into the proteome. In the last section, it focuses on using chemical strategies to study protein post-translational modifications and high-order structures. Summarizes chemical proteomics, up-to-date concepts, analysis, and target validation Covers fundamentals and strategies, including the profiling of enzyme activities and protein-drug interactions Explains technical advances in the field and describes on shotgun proteomics, quantitative proteomics, and corresponding methods of software and database usage for proteomics Includes a wide variety of applications in drug discovery, from kinase inhibitors and intracellular drug targets to the chemoproteomics analysis of natural products Addresses an important tool in small molecule drug discovery, appealing to both academia and the pharmaceutical industry Mass Spectrometry-Based Chemical Proteomics is an excellent source of information for readers in both academia and industry in a variety of fields, including pharmaceutical sciences, drug discovery, molecular biology, bioinformatics, and analytical sciences.
