Therapeutic Enzymes Function And Clinical Implications

Therapeutic enzymes exhibit fascinating features and opportunities, and represent a significant and promising subcategory of modern biopharmaceuticals for the treatment of several severe diseases. Research and drug developments efforts and the advancements in biotechnology over the past twenty years have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of both rare and common disorders. The introduction and regulatory approval of twenty different recombinant enzymes has enabled effective enzyme-replacement therapy. This volume aims to overview these therapeutic enzymes, focusing in particular on more recently approved enzymes produced by recombinant DNA technology. This volume is composed of four sections. Section 1 provides an overview of the production process and biochemical characterization of therapeutic enzymes, while Section 2 focuses upon the engineering strategies and delivery methods of therapeutic enzymes. Section 3 highlights the clinical applications of approved therapeutic enzymes, including aspects on their structure, indications and mechanisms of action. Together with information on these mechanisms, safety and immunogenicity issues and various adverse events of the recombinant enzymes used for therapy are discussed. Section 4, provides discussion on the prospective and future developments of new therapeutic enzymes. This book is aimed at academics, researchers and students undertaking advanced undergraduate/postgraduate programs in the biopharmaceutical/biotechnology area who wish to gain a comprehensive understanding of enzyme-based therapeutic molecules.

Biotechnology of Microbial Enzymes: Production, Biocatalysis, and Industrial Applications, Second Edition provides a complete survey of the latest innovations on microbial enzymes, highlighting biotechnological advances in their production and purification along with information on successful applications as biocatalysts in several chemical and industrial processes under mild and green conditions. The application of recombinant DNA technology within industrial fermentation and the production of enzymes over the last three decades have produced a host of useful chemical and biochemical substances. The power of these technologies results in novel transformations, better enzymes, a wide variety of applications, and the unprecedented development of biocatalysts through the ongoing integration of molecular biology methodology, all of which is covered insightfully and in-depth within the book. This fully revised, second edition is updated to address the latest research developments and applications in the field, from microbial enzymes recently applied in drug discovery to penicillin biosynthetic enzymes and penicillin acylase, xylose reductase, and microbial enzymes used in antitubercular drug design. Across the chapters, the use of microbial enzymes in sustainable development and production processes is fully considered, with recent successes and ongoing challenges highlighted. Explores advances in microbial enzymes from basic science through application in multiple industry sectors Includes up-to-date discussions of metabolic pathway engineering, metagenomic screening, microbial genomes, extremophiles, rational design, directed evolution, and more Provides a holistic approach to the research of microbial enzymes and their use in sustainable processes and innovation Features all new chapters discussing microbial enzyme classes of growing interest, as well as enzymes recently applied in drug discovery and other applications

This up-to-date reference book discusses the synthesis, production, and application of various microbial enzymes and metabolites for health. Microorganisms like bacteria (lactic acid bacteria, Bacillus species), yeasts, and filamentous fungi have been globally exploited for their biotechnological applications. This book discusses ways to use them commercially. Chapters include the production of fibrinolytic enzymes, microbial lipases, bacteriocin production by lactic acid bacteria, and bioactives produced. It also covers microbial synthesis of alkaloids, terpenoids, and steroids. This book is useful for researchers, academicians, and industry experts in microbiology and biotechnology.

“Biobetters: Protein Engineering to Approach the Curative” discusses the optimization of protein therapeutic products for treatment of human diseases. It is based on the fact that though numerous important therapeutic protein products have been developed for life threatening and chronic diseases that possess acceptable safety and efficacy profiles, these products have generally not been reexamined and modified for an improved clinical performance, with enhancements both to safety and efficacy profiles. Advances in protein engineering, coupled with greatly enhanced understanding of critical product quality attributes for efficacy and safety, make it possible to optimize predecessor products for clinical performance, thereby enhancing patient quality of life and with the potential for great savings in health care costs. Yet despite such knowledge, there is little movement towards such modifications. This book examines engineering protein therapeutic products such that they exhibit an optimal, not just an adequate, clinical performance profile. Two product classes, therapeutic enzymes for lysosomal storage diseases (enzyme replacement therapies, ERT) and monoclonal antibodies (mAbs), are used as examples of what modifications to such proteins could be made to enhance clinical performance, “closer to a cure” as it were. For ERT, the key to optimizing clinical performance is to ensure the ERT is endowed with moieties that target the protein to the relevant target tissue. Thus, for Gaucher Disease, our best example of how to optimize an ERT to address a disease that manifests in specific target tissues (macrophages and monocytes), the enzyme has been extensively modified to target macrophages. For diseases such as Pompe Disease, largely a disorder of muscle, optimal performance of ERT will depend on endowing the enzyme with the ability to be taken up via the Mannose 6 Phosphate Receptor, and so one of the chapters in the book will discuss such approaches. Moreover, a major failure of biotechnology based products is to gain access to the CNS, a key target tissue in numerous diseases. Thus, a chapter has been devoted to strategies to access the CNS. Additionally, immune responses to therapeutic proteins can be highly problematic, eliminating the efficacy of life saving or highly effective protein therapeutics. This is especially poignant in the case of Pompe Disease wherein great improvement in muscle strength and functionality is lost following development of an immune response to the ERT with consequent patient deterioration and death. Thus, a chapter regarding protein engineering, as well as other non-clinical approaches to diminishing immunogenicity is a valuable part of the book. Monoclonal antibodies (mAbs) can be engineered to bind targets relevant to a wide variety of diseases; binding affinity, however, is only part of the equation and one of the chapters will present a molecular assessment approach that balances affinity with pharmacokinetics and manufacturability. As with other proteins immunogenicity can be problematic, being responsible for loss of efficacy of anti-TNF mAbs, often after prolonged successful treatment. The authors will also share their perspective on the consequences of physico-chemical modifications occurring to mAbs once they reach the circulation or their target, a research area open to further development from a protein engineering as well as analytical perspective. This book will also discuss novel platforms for protein therapeutics, technologies that exceed mAbs with respect to potency, and hence, potentially efficacy. These platforms consist largely of repeat domain proteins with very high affinity for their target ligands, but while potentially more efficacious, immunogenicity may be a major problem limiting use. The economics surrounding the issue of biobetters is another high-profile issue - this final chapter will explore the incentives and disincentives for developing biobetters and consider incentives that might make their pursuit more rewarding.

Green Sustainable Process for Chemical and Environmental Engineering and Science: Solvents for the Pharmaceutical Industry aims at providing a detailed overview of applications of green solvents in pharmaceutical industries. It also focuses on providing a detailed literature survey on the green solvents for pharmaceutical analysis, drug design, synthesis, and production, etc. It summarizes the applications of various greens solvents such as water, cyrene, vegetable oils, ionic liquids, ethyl lactate, eutectic solvents, and glycerol in contrast to toxic solvents. This book provides an overview of the use of green solvents for the sustainable and environmentally friendly development of synthetic methodologies for biomedical and pharmaceutical industries. Up-to-date developments towards the development of solvents for pharmaceutical industry Includes latest advances in pharmaceutical analysis and synthesis using green solvents Outlines eco-friendly green solvents for medicinal applications State-of-the-art overview on the exploration of green solvents for pharmaceutical industries

Carbohydrate-Based Therapeutics Comprehensive resource summarizing opportunities and latest progress in design methodologies for carbohydrate-based therapeutics through a disease-oriented approach Carbohydrate-Based Therapeutics covers current progress and explores new frontiers in carbohydrate-based therapeutic applications, utilizing a unique approach by providing a detailed background of diseases coupled with subsequent carbohydrate-based therapies. The link between chemistry and design of novel carbohydrate-based medicines is highlighted and a broad overview of all the potential applications of carbohydrates is given. Emphasis is laid on concepts used for carbohydrate drug design, structure– activity relationship, and impact on health and diseases. The text also discusses newer topics like nanoparticles, material science, and tissue generation. Carbohydrate-Based Therapeutics includes information on: Antimicrobial carbohydrate-based therapies, covering antibacterial and antiviral vaccines, antifungal therapies, anti-influenza therapeutics, and antiadhesive carbohydrates and glycomimetics Anti-cancer carbohydrate-based therapies, covering cancer vaccines and immunotherapy, and carbohydrate tools in cancer biology Carbohydrate-based therapies in metabolic, neuronal, and immune disorders, covering carbohydrate-based therapeutics for lysosomal disorders and neurodegenerative diseases New frontiers in carbohydrate-based therapies, covering carbohydrates for tissue engineering, antiangiogenic and regenerative medicine Providing comprehensive coverage of foundational knowledge on the subject in a unique and highly accessible format while also exploring the state of the art in the field’s applications, Carbohydrate-Based Therapeutics is an essential resource for medicinal, pharmaceutical, and organic chemists, chemists in industry, biochemists, and biotechnologists.