Protein Homeostasis In Drug Discovery

Author : Milka Kostic
Publisher : John Wiley & Sons
ISBN 13 : 1119774128
Total Pages : 564 pages
Book Rating : 4.29/5 ( download)

DOWNLOAD NOW!

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.

Author : Milka Kostic
Publisher : John Wiley & Sons
ISBN 13 : 1119774187
Total Pages : 564 pages
Book Rating : 4.81/5 ( download)

DOWNLOAD NOW!

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.

Author : Craig Crews
Publisher : Royal Society of Chemistry
ISBN 13 : 1788016866
Total Pages : 382 pages
Book Rating : 4.65/5 ( download)

DOWNLOAD NOW!

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.

Author : Lalima G. Ahuja
Publisher : de Gruyter
ISBN 13 : 9783110426434
Total Pages : 0 pages
Book Rating : 4.39/5 ( download)

DOWNLOAD NOW!

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

Author : Evert Njomen
Publisher :
ISBN 13 :
Total Pages : 205 pages
Book Rating : 4.96/5 ( download)

DOWNLOAD NOW!

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.

Author : Richard I. Morimoto
Publisher :
ISBN 13 : 9781936113064
Total Pages : 0 pages
Book Rating : 4.66/5 ( download)

DOWNLOAD NOW!

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.

Author : Christopher Patrick Tinworth
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.99/5 ( download)

DOWNLOAD NOW!

Download or read book Targeted Protein Degradation as a New Approach to Drug Discovery written by Christopher Patrick Tinworth and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Author : Benjamin F. Cravatt
Publisher : Springer
ISBN 13 : 3030111431
Total Pages : 417 pages
Book Rating : 4.34/5 ( download)

DOWNLOAD NOW!

Download or read book Activity-Based Protein Profiling written by Benjamin F. Cravatt and published by Springer. This book was released on 2019-01-25 with total page 417 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides a collection of contemporary perspectives on using activity-based protein profiling (ABPP) for biological discoveries in protein science, microbiology, and immunology. A common theme throughout is the special utility of ABPP to interrogate protein function and small-molecule interactions on a global scale in native biological systems. Each chapter showcases distinct advantages of ABPP applied to diverse protein classes and biological systems. As such, the book offers readers valuable insights into the basic principles of ABPP technology and how to apply this approach to biological questions ranging from the study of post-translational modifications to targeting bacterial effectors in host-pathogen interactions.

Author : Gerard Drewes
Publisher : Humana Press
ISBN 13 : 9781617793639
Total Pages : 0 pages
Book Rating : 4.39/5 ( download)

DOWNLOAD NOW!

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.

Author : Angel L. Pey
Publisher : Academic Press
ISBN 13 : 0128191333
Total Pages : 450 pages
Book Rating : 4.30/5 ( download)

DOWNLOAD NOW!

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 450 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