Download or read book Therapeutic Potential of Furin Inhibition written by Jeroen Declercq and published by Biota Publishing. This book was released on 2012-10-01 with total page 32 pages. Available in PDF, EPUB and Kindle. Book excerpt: The proprotein convertase Furin is a serine endoprotease which cleaves protein precursors carboxyterminal of basic residues in motifs such as Arg–X–X–Arg and Lys/Arg–Arg. Cleavage usually results in activation of the proprotein but can also inactivate or modify the activity. Therefore, it is not surprising that it plays a major role in many physiological processes and pathologies, including cancer. The other proprotein convertases belonging to the same family, PC1/3, PC2, PACE4, PC4, PC5/6, and PC7, cleave at similar cleavage sites and provide partial redundancy. To unravel the specific role of Furin in vivo, knockout mouse models have been generated. Furin null mice die between e10.5 and e11.5 due to severe ventral closure defects and the failure of the heart tube to fuse and undergo looping morphogenesis. Therefore, a conditional Furin knockout mouse was generated to investigate the role of Furin in specific organs, such as pancreas, liver, T-cells, endothelial cells, and salivary glands, resulting in a severe or mild phenotype depending on the organ investigated. Partial or complete ablation of the Fur gene in salivary gland tumors significantly delayed tumorigenesis in mice. Therefore, Furin inhibition might be considered as a possible therapeutic strategy to treat certain pathologies, such as cancer.
Download or read book Activation of Viruses by Host Proteases written by Eva Böttcher-Friebertshäuser and published by Springer. This book was released on 2018-05-22 with total page 337 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book will give an overview on viruses undergoing proteolytic activation through host proteases. The chapters will be organized in three themed parts, the first part describing respective viruses and their characteristics in detail. In the second part the molecular and cellular biology of the proteases involved as well as their physiological functions will be further explored. The third part will contain a chapter on protease inhibitors that are promising tools for antiviral therapy. This book will engage scholars in virology and medical microbiology as well as researchers with an interest in enzymology and protein structure and function relationship.
Download or read book Pathophysiological Aspects of Proteases written by Sajal Chakraborti and published by Springer. This book was released on 2017-11-15 with total page 668 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive overview of the multifaceted field of protease in the cellular environment and focuses on the recently elucidated functions of complex proteolytic systems in physiology and pathophysiology. Given the breadth and depth of information covered in the respective contributions, the book will be immensely useful for researchers working to identify targets for drug development. Multidisciplinary in scope, the book bridges the gap between fundamental and translational research, with applications in the biomedical and pharmaceutical industry, making it a thought-provoking read for basic and applied scientists engaged in biomedical research. Proteases represent one of the largest and most diverse families of enzymes known, and we now know that they are involved in every aspect of a given organism’s life functions. Under physiological conditions, proteases are regulated by their endogenous inhibitors. However, when the activity of proteases is not correctly regulated, disease processes such as tumour progression, vascular remodelling, atherosclerotic plaque progression, ulcer, rheumatoid arthritis, Alzheimer’s disease and inflammation can result. Many infective microorganisms require proteases for replication or use them as virulence factors, which has facilitated the development of protease-targeted therapies for a variety of parasitic diseases.
Download or read book Matrix Metalloproteinase Inhibitors in Cancer Therapy written by Neil J. Clendeninn and published by Springer Science & Business Media. This book was released on 2000-09-17 with total page 371 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials. Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.
Download or read book Extracellular Matrix and Egg Coats written by and published by Academic Press. This book was released on 2018-05-28 with total page 504 pages. Available in PDF, EPUB and Kindle. Book excerpt: Extracellular Matrix and Egg Coats, Volume 130, the latest release in the Current Topics in Developmental Biology series, highlights new advances in the field, with this new volume presenting interesting chapters on The Human Egg's Zona Pellucida, the Structure of Zona Pellucida Module Proteins, The Fish Egg's Zona Pellucidam The Chicken Egg's Zona Pellucidam The Marsupial Egg's Zona Pellucida, the Evolution of Zona Pellucida Proteins, The Mouse Egg's Zona Pellucida, Aspects of ECM, ECM and Morphogenesis, Collagen fibril assembly and function, The Ear's Tectorial Membrane, ECM and Cell Fate, and the Aspects of ECM. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in the Current Topics in Developmental Biology series - Updated release includes the latest information on the Extracellular Matrix in Development
Download or read book In Silico Modeling of Drugs Against Coronaviruses written by Kunal Roy and published by . This book was released on 2021 with total page 788 pages. Available in PDF, EPUB and Kindle. Book excerpt: This essential volume explores a variety of tools and protocols of structure-based (homology modeling, molecular docking, molecular dynamics, protein-protein interaction network) and ligand-based (pharmacophore mapping, quantitative structure-activity relationships or QSARs) drug design for ranking and prioritization of candidate molecules in search of effective treatment strategy against coronaviruses. Beginning with an introductory section that discusses coronavirus interactions with humanity and COVID-19 in particular, the book then continues with sections on tools and methodologies, literature reports and case studies, as well as online tools and databases that can be used for computational anti-coronavirus drug research. Written for the Methods in Pharmacology and Toxicology series, chapters include the kind of practical detail and implementation advice that ensures high quality results in the lab. Comprehensive and timely, In Silico Modeling of Drugs Against Coronaviruses: Computational Tools and Protocols is an ideal reference for researchers working on the development of novel anti-coronavirus drugs for SARS-CoV-2 and for coronaviruses that will likely appear in the future.
Download or read book British Columbia in the Making 1913 written by John Bensley Thornhill and published by London : Constable. This book was released on 1913 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Novel Pharmacological Inhibitors for Bacterial Protein Toxins written by Holger Barth and published by MDPI. This book was released on 2018-07-09 with total page 125 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "Novel Pharmacological Inhibitors for Bacterial Protein Toxins" that was published in Toxins
Download or read book Anthrax in Humans and Animals written by World Health Organization and published by World Health Organization. This book was released on 2008 with total page 219 pages. Available in PDF, EPUB and Kindle. Book excerpt: This fourth edition of the anthrax guidelines encompasses a systematic review of the extensive new scientific literature and relevant publications up to end 2007 including all the new information that emerged in the 3-4 years after the anthrax letter events. This updated edition provides information on the disease and its importance, its etiology and ecology, and offers guidance on the detection, diagnostic, epidemiology, disinfection and decontamination, treatment and prophylaxis procedures, as well as control and surveillance processes for anthrax in humans and animals. With two rounds of a rigorous peer-review process, it is a relevant source of information for the management of anthrax in humans and animals.
Download or read book The Endothelium written by Michel Félétou and published by Morgan & Claypool Publishers. This book was released on 2011 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt: The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References
Download or read book Drug Design written by Gerhard Klebe and published by Springer. This book was released on 2013-07-10 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Unique work on structure-based drug design, covering multiple aspects of drug discovery and development. Fully colored, many images, computer animations of 3D structures (these only in electronic form). Makes the spatial aspects of interacting molecules clear to the reader, covers multiple applications and methods in drug design. Structures by mode of action, no therapeutic areas. Of high relevance for academia and industrial research. Focus on gene technology in drug design, omics-technologies computational methods experimental techniques of structure determination multiple examples on mode of action of current drugs, ADME-tox properties in drug development, QSAR methods, combinatorial chemistry, biologicals, ribosome, targeting protein-protein interfaces.
Download or read book Coronaviruses written by Helena J. Maier and published by Humana. This book was released on 2021-09-08 with total page 278 pages. Available in PDF, EPUB and Kindle. Book excerpt: This detailed new edition provides a comprehensive collection of protocols applicable to all members of the Coronavirinae sub-family currently and that are also transferrable to other fields of virology. Beginning with a section on detection, discovery, and evolution, the volume continues with coverage of propagation and titration of coronaviruses, genome manipulation, study of virus-host interactions, as well as imaging coronavirus infections. 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 cutting-edge, Coronaviruses: Methods and Protocols, Second Edition serves as a valuable guide to researchers working to identify and control viruses with increased potential to cross the species barrier and to develop the diagnostics, vaccines, and antiviral therapeutics that are required to manage future outbreaks in both humans and animals.
Download or read book MERS CoV written by Fang Li and published by MDPI. This book was released on 2019-12-12 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt: Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic coronavirus. First identified in 2012, MERS-CoV has caused over 2460 infections and a fatality rate of about 35% in humans. Similar to severe acute respiratory syndrome coronavirus (SARS-CoV), MERS-CoV likely originated from bats; however, different from SARS-CoV, which potentially utilized palm civets as its intermediate hosts, MERS-CoV likely transmits to humans through dromedary camels. Animal models, such as humanized mice and nonhuman primates, have been developed for studying MERS-CoV infection. Currently, there are no vaccines and therapeutics approved for the prevention and treatment of MERS-CoV infection, although a number of them have been developed preclinically or tested clinically. This book covers one editorial and 16 articles (including seven review articles and nine original research papers) written by researchers working in the field of MERS-CoV. It describes the following three main aspects: (1) MERS-CoV epidemiology, transmission, and pathogenesis; (2) current progress on MERS-CoV animal models, vaccines, and therapeutics; and (3) challenges and future prospects for MERS-CoV research. Overall, this book will help researchers in the MERS-CoV field to further advance their work on the virus. It also has important implications for other coronaviruses as well as viruses outside the coronavirus family with pandemic potentials.
Download or read book The Proprotein Convertases written by Abdel-Majid Khatib and published by Morgan & Claypool Publishers. This book was released on 2013-02 with total page 89 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proprotein convertases (PCs) are a family of proteases including PC1, PC2, Furin, PC4, PACE4, PC5, and PC7. These enzymes are involved in the maturation of many precursor proteins involved in the process of tumorigenesis and metastasis. Since their discovery, PCs were suggested as potential targets for anti-cancer therapy, and their activity was found to directly affect tumor cell proliferation, migration invasion, and the malignant phenotypes of tumor cells. Here, we discuss a number of previous and recent findings on the PCs features, their implication in the regulation of multiple cellular functions that impact on the invasive/metastatic potential of cancer cells, and their clinical relevance in cancer patients. Among the substrates of the proprotein convertases, various growth factors, their receptors, adhesion molecules, and proteases were identified. The PCs are inhibited by endogenous and exogenous inhibitors. To date, only pro7B2, a specific chaperone of PC2, and the granine-like precursor of neuroendocrine protein proSAAS, a selective ligand of PC1, have been identified as endogenous inhibitors of the PCs found in the regulated pathway. However, only PCs prosegments, several bioengineered inhibitors, peptides, and non-peptide compounds were found to inhibit the activity of the PCs found in the secretory pathway.
Download or read book Intramolecular Chaperones and Protein Folding written by Ujwal Shinde and published by . This book was released on 1995 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Textbook of Influenza written by Robert G. Webster and published by John Wiley & Sons. This book was released on 2014-01-06 with total page 684 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Textbook of Influenza is a comprehensive resource covering all aspects of influenza, from the genetic and molecular biology of the virus through to clinical aspects of the disease and the latest drug developments and treatments. This new edition has been completely revised and reflects the integration of disciplines concerning the emergence, evolution, pathogenesis and control of influenza viruses in the field of human and veterinary public health. Textbook of Influenza examines the lessons learnt from the latest pandemic and provides the current state of knowledge for many yet unresolved issues related to virus origin, spread, pathogenesis and disease severity to better prepare for future pandemics. It covers the background to recent advances in influenza genomics and reverse genetics which have allowed the identification of virus virulence factors and the analysis and reconstruction of influenza viruses such as the 1918 Spanish flu strain. This new edition is divided into eight key sections, containing chapters co-written by international experts from both the clinical and scientific communities, covering: • Influenza Perspectives • Structure and Replication • Evolution and Ecology • Epidemiology and Surveillance • Immunology • Vaccines and Vaccine Development • Clinical Aspects and Antivirals • Public Health Textbook of Influenza is for all those working in the area of influenza including clinical and basic scientists, immunologists, molecular and structural virologists, public health officials and global pandemic control planners.
Download or read book Non peptide Inhibitors of Proprotein Convertase Subtilisin Kexins PCSKs written by Utpal Chandra De and published by Biota Publishing. This book was released on 2012-10-01 with total page 78 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Ca+2-dependent mammalian Proprotein Convertase Subtilisin Kexins (PCSKs) or Proprotein/ Prohormone Convertases (PCs) are a family of endoproteases that play critical roles not only in normal development and metabolism but also in various physiological and pathological conditions. These were initiated by the proteolytic processing of large inactive proproteins into their shorter bioactive mature forms by the PCSK enzymes. These events take place in a highly selective, orchestrated, and stepwise manner. Among the various proprotein substrates of PCSK enzymes, particularly important are the precursor growth factors that include proPDGF-A, B, proIGF-1, 2 and proVEGF-C because of their strong implications in neoplasia initiation, progression, and metastasis. As a result of these findings, PCSK enzymes, particularly furin or PCSK3, became a major target for possible interventions of cancer via the use of their selective inhibitors. Significant progress has been accomplished in the development of peptide and protein-based PCSK inhibitors. However, non-peptide PCSK9 inhibitors are more preferable because of their drug-like and other characteristics. So far, a few non-peptide inhibitors of PCSK enzymes of various types of chemical structures have been described in the literature. These include (i) Carbocyclic compounds of diterpene and streptamine class. (ii) Nitrogen (N)-based heterocyclic compounds of various types and chemical structures such as (a) pyrrolidine bis piperazines, (b) Cu/Zn chelating terpyridine derivatives; (iii) Oxygen (O)-based Heterocyclic compounds of varying types of chemical structures such as (a) Flavonoids, (b) Coumarins of simple and dimeric types, (c) Quinonoids, (d) Iridoids; (iv) Aromatic compounds such as (a) Aryl guanidino and amidino derivatives, (b) Naphthyl fluorescein derivative, and (c) Phenyl Arsonic acids; and (v) C2-symmetrical aromatic azo-compounds. When measured against a small peptidyl-MCA fluorogenic substrate, these inhibitors displayed IC50 values ranging from nM to μM. A number of these inhibitors exhibited significant anti-PCSK activity when tested in ex vivo or cell culture conditions. This article provides an overall review of all non-peptide PCSK inhibitors so far reported in the literature along with those we identified recently for the first time and not yet published. The potential implications of these molecules as biochemical, therapeutical, or clinical agents will also be discussed.
