Brings together functional and structural informationrelevant to the design of drugs targeting zinc enzymes The second most abundant transition element in living organisms, zinc spans all areas of metabolism, with zinc-containing proteins offering both established and potential drug targets. Drug Design of Zinc-Enzyme Inhibitors brings together functional and structural information relevant to these zinc-containing targets. With up-to-date overviews of the latest developments field, this unique and comprehensive text enables readers to understand zinc enzymes and evaluate them in a drug design context. With contributions from the leaders of today's research, Drug Design of Zinc-Enzyme Inhibitors covers such key topics as: Major drug targets like carbonic anhydrases, matrix metalloproteinases, bacterial proteases, angiotensin-converting enzyme, histone deacetylase, and APOBEC3G Roles of recently discovered zinc-containing isozymes in cancer, obesity, epilepsy, pain management, malaria, and other conditions Cross reactivity of zinc-enzyme inhibitors and activators The extensive use of X-ray crystallography and QSAR studies for understanding zinc-containing proteins Clinical applications An essential resource for the discovery and development of new drug molecules, Drug Design of Zinc-Enzyme Inhibitors gives researchers, professionals, students, and academics the foundation to understand and work with zinc enzyme inhibitors and activators.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

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.

This book offers deep insights into the thermodynamics and molecular structures of the twelve catalytically active isoforms of human carbonic anhydrase (CA) with a particular focus on inhibitor binding for drug design. X-ray crystallographic structures in combination with enzyme kinetic testing provide information on the interaction of CAs and their inhibitors, knowledge which is crucial for rational drug design. CAs are zinc carrying enzymes that catalyse the reversible interconversion of carbon dioxide and bicarbonate and are involved in numerous cellular processes. They are therefore a common target for drugs. The suppression of CA activities through inhibitory compounds has found application for example in diuretics and in glaucoma therapy. In this book methods used to determine binding thermodynamics of inhibitory compounds (Isothermal titration calorimetry, Fluorescent thermal shift assay/differential scanning fluorimetry and others) will be compared in detail. Also types and chemical synthesis of CA inhibitors, the use of antibodies against CAs as well as inhibitor application in animals are discussed.

Our biological system is enriched with enzyme-catalyzed (or enzymatic) reactions that mediate a great multitude of life processes such as gene transcription and metabolism, and the inappropriately up-regulated activity of these enzymatic reactions is a major cause of human diseases such as cancer and metabolic diseases. Therefore, the inhibitors of enzymatic reactions (generally called enzyme inhibitors) constitute a major class of therapeutic agents on the global drug market. One question would then be how to efficiently design enzyme inhibitors. This handbook is the first of its kind in the field, introducing to its readers in a single book the concepts whose exploitation has been demonstrated to be successful in efficiently furnishing effective active site-directed inhibitors for various enzymatic reactions. The book is organized by different concepts and for each concept there is a delineation of its mode of working and its applications with different types of enzymatic reactions. Active Site-directed Enzyme Inhibitors will help its readers to quickly and efficiently obtain effective active site-directed inhibitors for any of the enzymatic reactions under study without a need to resort to library screening- and biostructure-based techniques. This handbook is ideal as an immediate resource for researchers to consult or for students to supplement their study in medicinal chemistry and related courses.

A collection of essays examining the major target enzymes and their inhibitors. The underlying physical and chemical processes of enzyme inhibition, the principles of inhibitor design using computer-based techniques, and clinical applications are described.

Zinc-dependent enzymes; HDAC; LpxC; computer-aided drug design; molecular modeling; homology modeling; molecular docking; binding free energy calculations; virtual screening; antiparasitic