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Author: Trent A. Kunkle Publisher: ISBN: Category : Languages : en Pages : 146
Book Description
The Centers for Disease Control (CDC) and World Health Organizations (WHO) have highlighted six species of highly drug-resistant bacteria, commonly termed the ESKAPE pathogens, that new antibacterials are urgently needed to treat). The ESKAPE pathogens account for over two-million infections and have healthcare costs upwards of $20 billion dollars annually. Over the past several decades, pharmaceutical companies have drastically reduced their research programs for developing new antibacterial agents. As well, bacteria are predisposed to rapidly generate resistance against these "me too" drugs, making this strategy a temporary stop-gap in our ability to fight these pathogens. This has left the burden to identify new antibiotics that function through fundamentally unique mechanisms of action to academia. Towards this goal, we are developing a unique antibacterial strategy that functions through targeting the bacterial GroEL chaperonin systems. GroEL is a molecular chaperone that helps fold proteins into their functional states. Being an essential protein, inhibiting GroEL activity leads to global aggregation and bacterial cell death. We previously reported a high-throughput screening effort that identified 235 GroEL inhibitors. A subsequent study with a subset of these inhibitors identified several that kill bacteria. To follow-up, we have synthesized 43 analogs of a hit-to-lead molecule, compound 1, containing systematic deletions of substituents and substructures to determine the essential parts of the scaffold for inhibiting GroEL and killing bacteria. Along with inhibiting GroEL, several compound 1 analogs exhibit>50-fold therapeutic windows between antibacterial efficacy and cytotoxicity to human liver and kidney cells in cell culture. Evaluation of two lead candidates (1 and 11) in a gain-of-resistance assay indicated that MRSA bacteria were not able to easily generate resistance to this compound class. Compound 1 also exhibited the ability to permeate through already established S. aureus biofilms and maintain its bactericidal effects, whereas vancomycin could not. Having established initial structure-activity relationships for the compound 1 substituents and substructures in this study, future efforts will focus on optimizing the antibacterial effects of lead candidates and reducing their off-target toxicity to human cells
Author: Trent A. Kunkle Publisher: ISBN: Category : Languages : en Pages : 146
Book Description
The Centers for Disease Control (CDC) and World Health Organizations (WHO) have highlighted six species of highly drug-resistant bacteria, commonly termed the ESKAPE pathogens, that new antibacterials are urgently needed to treat). The ESKAPE pathogens account for over two-million infections and have healthcare costs upwards of $20 billion dollars annually. Over the past several decades, pharmaceutical companies have drastically reduced their research programs for developing new antibacterial agents. As well, bacteria are predisposed to rapidly generate resistance against these "me too" drugs, making this strategy a temporary stop-gap in our ability to fight these pathogens. This has left the burden to identify new antibiotics that function through fundamentally unique mechanisms of action to academia. Towards this goal, we are developing a unique antibacterial strategy that functions through targeting the bacterial GroEL chaperonin systems. GroEL is a molecular chaperone that helps fold proteins into their functional states. Being an essential protein, inhibiting GroEL activity leads to global aggregation and bacterial cell death. We previously reported a high-throughput screening effort that identified 235 GroEL inhibitors. A subsequent study with a subset of these inhibitors identified several that kill bacteria. To follow-up, we have synthesized 43 analogs of a hit-to-lead molecule, compound 1, containing systematic deletions of substituents and substructures to determine the essential parts of the scaffold for inhibiting GroEL and killing bacteria. Along with inhibiting GroEL, several compound 1 analogs exhibit>50-fold therapeutic windows between antibacterial efficacy and cytotoxicity to human liver and kidney cells in cell culture. Evaluation of two lead candidates (1 and 11) in a gain-of-resistance assay indicated that MRSA bacteria were not able to easily generate resistance to this compound class. Compound 1 also exhibited the ability to permeate through already established S. aureus biofilms and maintain its bactericidal effects, whereas vancomycin could not. Having established initial structure-activity relationships for the compound 1 substituents and substructures in this study, future efforts will focus on optimizing the antibacterial effects of lead candidates and reducing their off-target toxicity to human cells
Author: Alexzander A. A. Asea Publisher: Springer Nature ISBN: 3030231542 Category : Science Languages : en Pages : 363
Book Description
The book Heat Shock Protein 60 in Human Diseases and Disorders provides the most comprehensive review on contemporary knowledge on the role of HSP60 in human diseases and disorders. Using an integrative approach, the contributors provide a synopsis of novel mechanisms and signal transduction pathways. To enhance the ease of reading and comprehension the book has further been subdivided into various section including; Section I: Biomolecular Aspects of HSP60; Section II: HSP60 and Cancer; Section III: HSP60 and Inflammatory Diseases and Disorders; Section IV: HSP60 and Cardiovascular Diseases and Disorders; Section V: HSP60 and Neurological and Neurosciences; Section VI: Biomolecular Aspects of HSP60; Section VII: HSP60 and Skeletal Muscle Diseases and Disorders; and Section VIII: HSP60 in Human Health. Key basic and clinical research laboratories from major universities, academic medical hospitals, biotechnology and pharmaceutical laboratories around the world have contributed chapters that review present research activity and importantly project the field into the future. The book is a must read for graduate students. medical students, basic science researchers and postdoctoral scholars in the fields of Translational Medicine, Clinical Research, Human Physiology, Biotechnology, Neurology & Neuroscience, Oncology, Cardiovascular Disease, Skeletal Muscle Diseases and Disorders, Cell & Molecular Medicine, Pharmaceutical Scientists and Researchers involved in Drug Discovery.
Author: Alberto J.L. Macario Publisher: Springer Science & Business Media ISBN: 9400746679 Category : Medical Languages : en Pages : 126
Book Description
This Brief provides a concise review of chaperonopathies, i.e., diseases in which molecular chaperones play an etiologic-pathogenic role. Introductory chapters deal with the chaperoning system and chaperoning teams and networks, HSP-chaperone subpopulations, the locations and functions of chaperones, and chaperone genes in humans. Other chapters present the chaperonopathies in general, including their molecular features and mechanistic classification into by defect, excess, or mistake. Subsequent chapters discuss the chaperonopathies in more detail, focusing on their distinctive characteristics: primary or secondary; quantitative and/or qualitative; structural and hereditary or acquired; genetic polymorphisms; gene dysregulation; age-related; associated with cancer, chronic inflammatory conditions, and autoimmune diseases. The interconnections between the chaperoning and the immune systems in cancer development, chronic inflammation, autoimmunity, and ageing are outlined, which leads to a discussion on the future prospects of chaperonotherapy. The latter may consist of chaperone gene and protein replacement/supplementation in cases of deficiency and of gene or protein blocking when the chaperone actively promotes disease. The last chapter presents the extracellular chaperones and details on how the chaperone Hsp60 is secreted into the extracellular space and, thus, appears in the blood of cancer patients with potential to participate in carcinogenesis and chronic inflammation and autoimmunity. Chaperones as clinically useful biomarkers are mentioned when pertinent. Likewise, guidelines for clinical evaluation of chaperonopathies and for their histopathological and molecular identification are provided throughout. The book also provides extensive bibliography organized by chapter and topic with comments.
Author: Anne Skaja Robinson Publisher: John Wiley & Sons ISBN: 3527634533 Category : Science Languages : en Pages : 631
Book Description
Designed as a research-level guide to current strategies and methods of membrane protein production on the small to intermediate scale, this practice-oriented book provides detailed, step-by-step laboratory protocols as well as an explanation of the principles behind each method, together with a discussion of its relative advantages and disadvantages. Following an introductory section on current challenges in membrane protein production, the book goes on to look at expression systems, emerging methods and approaches, and protein specific considerations. Case studies illustrate how to select or sample the optimal production system for any desired membrane protein, saving both time and money on the laboratory as well as the technical production scale. Unique in its coverage of "difficult" proteins with large membrane-embedded domains, proteins from extremophiles, peripheral membrane proteins, and protein fragments.
Author: D. A. Phoenix Publisher: ISBN: 9780691635989 Category : Languages : en Pages : 0
Book Description
Protein targeting is a fast-moving field that has encompassed areas from biophysics to molecular biology to try to gain insight into how proteins are directed to their final functional location and how such macromolecules are able to cross semi-permeable membrane barriers during their journey. This text reviews our current state of knowledge regarding the interaction of proteins at the membrane interface and the assembly of proteins into biological membranes, before proceeding to look at targeting pathways in both prokaryotic and eukaryotic systems. The reviews have been written by some of the leading researchers in the field, with contributions from around the world and with more than 1,800 references. The text is aimed at graduate students and at researchers with an interest in protein targeting, but may also be of use to final-year undergraduates. Originally published in 1999. The Princeton Legacy Library uses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These editions preserve the original texts of these important books while presenting them in durable paperback and hardcover editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905.
Author: Alexzander A A Asea Publisher: Springer ISBN: 3319747150 Category : Medical Languages : en Pages : 471
Book Description
This books provides the most up-to-date reviews on current advances in our understanding of the regulation of heat shock protein responses. Key basic scientists and clinical research laboratories from major universities, academic medical centers and pharmaceutical companies around the world have contributed chapters that review present research activity and importantly project this field into the future. For easy readability, the book is sub divided into four sections, including, Section I - HSP and Stress Responses; Section II - Chaperone Functions of HSP; Section III - HSP in Human Diseases; Section IV - Prognosis & Diagnosis of HSP. The book is a must read for researchers involved in biomedical research, drug discovery and design to improve human health.
Author: William R. Jacobs, Jr. Publisher: John Wiley & Sons ISBN: 1683673050 Category : Medical Languages : en Pages : 1379
Book Description
Can today's innovative practices and molecular tools tame this ancient disease? One third of the world's population is infected with tuberculosis (TB), with about 10 million new cases annually. To combat TB and its agent, Mycobacterium tuberculosis, the World Health Organization launched The End TB Strategy, which aims to slash the suffering and cost of TB by 2035. This makes the second edition of Tuberculosis and the Tubercle Bacillus, edited by Jacobs, McShane, Mizrahi, and Orme, an extremely valuable resource for scientists and clinicians. The editors have gathered their colleagues from around the world to present the latest on the molecular biology of M. tuberculosis and related species, the host-pathogen interactions that enable invasion, and the host's immune response to M. tuberculosis infection. The basic, clinical, and translational research presented in this book supports the goals of WHO's End TB Strategy by driving toward the development of effective vaccines, rapid molecular diagnostics, and anti-TB drugs. Creating an effective tuberculosis vaccine. Understand the innate and adaptive immune response to M. tuberculosis infection, its study in established animal models, and how this information is being used to develop new vaccines against TB. Formulating new antituberculosis drugs. Learn the challenges and methods for evaluating new drugs in preclinical trials with a focus on drugs that work against "persisters" and those that act on the electron transport complex and ATP synthase of M. tuberculosis. Overcoming the challenges of diagnosing tuberculosis. Review new diagnostic tools that are simple, rapid, affordable, specific, sensitive, and safe, including molecular-based diagnostic methods such as GeneXpert MTB/RIF. Using molecular, genomic, and bioinformatics tools to understand the biology and evolution of Mycobacterium. Explore current research on the molecular mechanisms that M. tuberculosis uses to evade the immune system, enter a state of nonreplicating persistence, and become reactivated. The second edition of Tuberculosis and the Tubercle Bacillus presents the latest research on a microorganism that is exquisitely well adapted to its human host. This pathogen continues to confound scientists, clinicians, and public health specialists, who will all find much valuable information in this comprehensive set of reviews.
Author: Moselio Schaechter Publisher: Academic Press ISBN: 0080961282 Category : Science Languages : en Pages : 1277
Book Description
The Desk Encyclopedia of Microbiology, Second Edition is a single-volume comprehensive guide to microbiology for the advanced reader. Derived from the six volume e-only Encyclopedia of Microbiology, Third Edition, it bridges the gap between introductory texts and specialized reviews. Covering topics ranging from the basic science of microbiology to the current "hot" topics in the field, it will be invaluable for obtaining background information on a broad range of microbiological topics, preparing lectures and preparing grant applications and reports. The most comprehensive single-volume source providing an overview of microbiology to non-specialists Bridges the gap between introductory texts and specialized reviews Provides concise and general overviews of important topics within the field making it a helpful resource when preparing for lectures, writing reports, or drafting grant applications
Author: Susan Buchanan Publisher: Humana ISBN: 9781493928705 Category : Science Languages : en Pages : 0
Book Description
This volume is comprised of a collection of experimental protocols for common techniques and strategies used to study the biogenesis of b-barrel outer membrane proteins in Gram-negative bacteria. The BAM Complex: Methods and Protocols guides readers through methods on the function of the BAM complex, the roles played by each of the individual components, the expression and purification of the components, crystallization and structure determination of the components, and how the individual Bam components may assemble into a functional complex. 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, The BAM Complex: Methods and Protocols will serve as an invaluable reference for those interested in studying the BAM complex.
Author: Errol C. Friedberg Publisher: American Society for Microbiology Press ISBN: 1555813194 Category : Science Languages : en Pages : 2587
Book Description
An essential resource for all scientists researching cellular responses to DNA damage. • Introduces important new material reflective of the major changes and developments that have occurred in the field over the last decade. • Discussed the field within a strong historical framework, and all aspects of biological responses to DNA damage are detailed. • Provides information on covering sources and consequences of DNA damage; correcting altered bases in DNA: DNA repair; DNA damage tolerance and mutagenesis; regulatory responses to DNA damage in eukaryotes; and disease states associated with defective biological responses to DNA damage.
Author: Trent A. Kunkle
Author: Trent A. Kunkle
Author: Alexzander A. A. Asea
Author: Alberto J.L. Macario
Author: Anne Skaja Robinson
Author: D. A. Phoenix
Author: Alexzander A A Asea
Author: William R. Jacobs, Jr.
Author: Moselio Schaechter
Author: Susan Buchanan
Author: Errol C. Friedberg