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Focusing on the development of enzyme inhibitors as therapeutic drugs, Enzymes and Their Inhibitors: Drug Development provides a concise overview of the chemistry of major types of enzymes and their inhibitors. The opening chapters introduce readers to the structure, functions, mechanisms, and kinetics of enzymes, including their use as disease mar
Vital information for discovering and optimizing new drugs "Understanding the data and the experimental details that support it has always been at the heart of good science and the assumption challenging process that leads from good science to drug discovery. This book helps medicinal chemists and pharmacologists to do exactly that in the realm of enzyme inhibitors." -Paul S. Anderson, PhD This publication provides readers with a thorough understanding of enzyme-inhibitor evaluation to assist them in their efforts to discover and optimize novel drug therapies. Key topics such as competitive, noncompetitive, and uncompetitive inhibition, slow binding, tight binding, and the use of Hill coefficients to study reaction stoichiometry are all presented. Examples of key concepts are presented with an emphasis on clinical relevance and practical applications. Targeted to medicinal chemists and pharmacologists, Evaluation of Enzyme Inhibitors in Drug Discovery focuses on the questions that they need to address: * What opportunities for inhibitor interactions with enzyme targets arise from consideration of the catalytic reaction mechanism? * How are inhibitors evaluated for potency, selectivity, and mode of action? * What are the advantages and disadvantages of specific inhibition modalities with respect to efficacy in vivo? * What information do medicinal chemists and pharmacologists need from their biochemistry and enzymology colleagues to effectively pursue lead optimization? Beginning with a discussion of the advantages of enzymes as targets for drug discovery, the publication then explores the reaction mechanisms of enzyme catalysis and the types of interactions that can occur between enzymes and inhibitory molecules that lend themselves to therapeutic use. Next are discussions of mechanistic issues that must be considered when designing enzyme assays for compound library screening and for lead optimization efforts. Finally, the publication delves into special forms of inhibition that are commonly encountered in drug discovery efforts, but can be easily overlooked or misinterpreted. This publication is designed to provide students with a solid foundation in enzymology and its role in drug discovery. Medicinal chemists and pharmacologists can refer to individual chapters as specific issues arise during the course of their ongoing drug discovery efforts.
Offers essential guidance for discovering and optimizing novel drug therapies Using detailed examples, Evaluation of Enzyme Inhibitors in Drug Discovery equips researchers with the tools needed to apply the science of enzymology and biochemistry to the discovery, optimization, and preclinical development of drugs that work by inhibiting specific enzyme targets. Readers will applaud this book for its clear and practical presentations, including its expert advice on best practices to follow and pitfalls to avoid. This Second Edition brings the book thoroughly up to date with the latest research findings and practices. Updates explore additional forms of enzyme inhibition and special treatments for enzymes that act on macromolecular substrates. Readers will also find new discussions detailing the development and application of the concept of drug-target residence time. Evaluation of Enzyme Inhibitors in Drug Discovery begins by explaining why enzymes are such important drug targets and then examines enzyme reaction mechanisms. The book covers: Reversible modes of inhibitor interactions with enzymes Assay considerations for compound library screening Lead optimization and structure-activity relationships for reversible inhibitors Slow binding and tight binding inhibitors Drug-target residence time Irreversible enzyme inactivators The book ends with a new chapter exploring the application of quantitative biochemical principles to the pharmacologic evaluation of drug candidates during lead optimization and preclinical development. The Second Edition of Evaluation of Enzyme Inhibitors in Drug Discovery continues to offer a treatment of enzymology applied to drug discovery that is quantitative and mathematically rigorous. At the same time, the clear and simple presentations demystify the complex science of enzymology, making the book accessible to many fields— from pharmacology to medicinal chemistry to biophysics to clinical medicine.
Soybean protei ns are wi de 1 y used inhuman foods ina vari ety of forms, including baby formulas, flour, soy protein concentrates, soy protein isolates, soy sauces, textured soy fibers, and tofu. The presence of inhibitors of digestive enzymes in soy proteins impairs nutritional quality and possible safety of this impportant legume. Normal processing conditions based on the use of heat do not completely inactivate these inhibitors, so that residual amounts of plant protease inhibitors are consumed by animals and man. Inhibitors of digestive enzymes are present not only in legumes, such as soybeans, lima beans, and kidney beans, but also in nearly all plant foods, including cereals and potatoes, albeit in much smaller amounts. The antinutritional effects of inhibitors of proteolytic enzymes have been widely studied and can be ameliorated by processing and/or sulfur amino acid fortification. A more urgent concern is reports that rats fed diets containing even low levels of soybean-derived inhibitors, which are found in foods such as soy-based baby formulas, may develop over their lifespan pancreatic lesions leading eventually to neoplasia or tumor formation. On the other hand, recent stUdies suggest that certain enzyme inhibitors from plant foods may prevent cancer formation in other tissues. A key question, therefore, is whether inhibitors from plant foods constitute a human health hazard.
Over the recent years, medicinal chemistry has become responsible for explaining interactions of chemical molecule processes such that many scientists in the life sciences from agronomy to medicine are engaged in medicinal research. This book contains an overview focusing on the research area of enzyme inhibitor and activator, enzyme-catalyzed biotransformation, usage of microbial enzymes, enzymes associated with programmed cell death, natural products as potential enzyme inhibitors, protease inhibitors from plants in insect pest management, peptidases, and renin-angiotensin system. The book provides an overview on basic issues and some of the recent developments in medicinal science and technology. Especially, emphasis is devoted to both experimental and theoretical aspect of modern medicine. The primary target audience for the book includes students, researchers, chemists, molecular biologists, medical doctors, pharmacologists, and professionals who are interested in associated areas. The textbook is written by international scientists with expertise in biochemistry, enzymology, molecular biology, and genetics, many of which are active in biochemical and pharmacological research. I would like to acknowledge the authors for their contribution to the book. We hope that the textbook will enhance the knowledge of scientists in the complexities of some medical approaches; it will stimulate both professionals and students to dedicate part of their future research in understanding relevant mechanisms and applications of pharmacology.
The application of biotechnology in the food sciences has led to an increase in food production and enhanced the quality and safety of food. Food biotechnology is a dynamic field and the continual progress and advances have not only dealt effectively with issues related to food security but also augmented the nutritional and health aspects of food. Advances in Food Biotechnology provides an overview of the latest development in food biotechnology as it relates to safety, quality and security. The seven sections of the book are multidisciplinary and cover the following topics: GMOs and food security issues Applications of enzymes in food processing Fermentation technology Functional food and nutraceuticals Valorization of food waste Detection and control of foodborne pathogens Emerging techniques in food processing Bringing together experts drawn from around the world, the book is a comprehensive reference in the most progressive field of food science and will be of interest to professionals, scientists and academics in the food and biotech industries. The book will be highly resourceful to governmental research and regulatory agencies and those who are studying and teaching food biotechnology.
Enzyme Inhibition and Bioapplications is a concise book on applied methods of enzymes used in drug testing. The present volume will serve the purpose of applied drug evaluation methods in research projects, as well as relatively experienced enzyme scientists who might wish to develop their experiments further. Chapters are arranged in the order of basic concepts of enzyme inhibition and physiological basis of cytochromes followed by new concepts of applied drug therapy; reliability analysis; and new enzyme applications from mechanistic point of view.
Enzyme inhibitors play a pivotal role in pharmaceutical and nutraceutical industries. The primary understanding of the action of inhibitors helps pharmacologists during the design process for developing new therapeutic drugs. Most drugs treat various chronic and life threatening diseases owing to their specificity and the potency of enzymes which they can inhibit. Enzyme inhibitors are used to screen various levels of diseases which propel the growth of inhibitors. The potential for enzyme inhibitors in the therapeutics market is very high as the biochemical properties and classes of enzyme inhibiting products are readily available. The other broad aspect of enzyme inhibition is their application in analytical sensors. These sensors assist in monitoring various environmental factors. Understanding the mechanism of inhibition and regeneration of enzymes is a general problem of great importance for many biochemists and biotechnologists especially when using immobilized enzymes. This reference compiles applied information about enzyme inhibitors used in medicine and environmental monitoring applications. Chapters presented in this volume cover special topics including biosensors, crop improvements in agriculture, biofuel production, pesticide and heavy metal detection, and drug therapy for human diseases such as breast cancer, neurological diseases and viral infections. The collection of topics in this volume makes it an informative resource for readers at all academic levels on the applications of enzyme inhibitors in medicine and environmental sciences.
The kinetic mechanisms by which enzymes interact with inhibitors and activators, collectively called modifiers, are scrutinized and ranked taxonomically into autonomous species in a way similar to that used in the biological classification of plants and animals. The systematization of the mechanisms is based on two fundamental characters: the allosteric linkage between substrate and modifier and the factor by which a modifier affects the catalytic constant of the enzyme. Combinations of the physically significant states of these two characters in an ancestor-descendant-like fashion reveal the existence of seventeen modes of interaction that cover the needs of total, partial and fine-tuning modulation of enzyme activity. These interactions comprise five linear and five hyperbolic inhibition mechanisms, five nonessential activation mechanisms and two hybrid species that manifest either hyperbolic inhibition or nonessential activation characteristics depending on substrate concentration. Five essential activation mechanisms, which are taxonomically independent of the mentioned basic species, complete the inventory of enzyme modifiers. Often masked under conventional umbrella terms or treated as anomalous cases, all seventeen basic inhibition and nonessential activation mechanisms are represented in the biochemical and pharmacological literature of this and the past century, either in the form of rapid or slow-onset reversible interactions, or as irreversible modification processes. The full potential of enzyme inhibitors and activators can only be appreciated after elucidating the details of their kinetic mechanisms of action exploring the entire range of physiologically significant reactant concentrations. This book highlights the wide spectrum of allosteric enzyme modification in physiological occurrences as well as in pharmacological and biotechnological applications that embrace simple and multiple enzyme-modifier interactions. The reader is guided in the journey through this still partly uncharted territory with the aid of mechanistically-oriented criteria aimed at showing the logical way towards the identification of a particular mechanism.
Enzymes in Food Biotechnology: Production, Applications, and Future Prospects presents a comprehensive review of enzyme research and the potential impact of enzymes on the food sector. This valuable reference brings together novel sources and technologies regarding enzymes in food production, food processing, food preservation, food engineering and food biotechnology that are useful for researchers, professionals and students. Discussions include the process of immobilization, thermal and operational stability, increased product specificity and specific activity, enzyme engineering, implementation of high-throughput techniques, screening to relatively unexplored environments, and the development of more efficient enzymes. Explores recent scientific research to innovate novel, global ideas for new foods and enzyme engineering Provides fundamental and advanced information on enzyme research for use in food biotechnology, including microbial, plant and animal enzymes Includes recent cutting-edge research on the pharmaceutical uses of enzymes in the food industry