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Research in the matrix metalloproteinase field began with the demonstration by Gross and Lapière, in 1962, that resorbing tadpole tail expressed an enzyme that could degrade collagen gels. These humble beginnings have led us to the elucidation of around twenty distinct vertebrate MMPs, along with a variety of homologs from such diverse organisms as sea urchin, plants, nematode worm, and bacteria. This, coupled with four known specific inhibitors of MMPs, the TIMPs, gives a complex picture. Part I of Matrix Metalloproteinase Protocols provides the reader with a selective overview of the MMP arena, and a chance to come to grips with where the field has been, where it is, and where it is going. I hope that this complements all of the methodology that comes later. Part II presents the reader with a diverse set of methods for the expression and purification of MMPs and TIMPs, bringing together the long and often hard-earned experience of a number of researchers. Part III allows the reader to detect MMPs and TIMPs at both the protein and mRNA level, whereas Part IV gives the ability to assay MMP and TIMP activities in a wide variety of circumstances.
Since the identification of the first matrix metalloprotease (insterstitial collagenase or MMP-1) more than 20 closely related and evolutionarily conserved vertebrate MMPs have been discovered. Chapters in this volume detail methods and protocols on recent advances in the expression and purification of MMPs, biophysical methods such as X-ray crystallography, NMR spectroscopy and small angle X-ray scattering, computational and experimental methods for determining MMP specificity, methods for detecting MMP activity in vitro and in vivo, and methods for the development and characterization of MMP-based inhibitors as potential therapeutics for the treatment of various diseases. 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 practical, Matrix Metalloproteases: Methods and Protocols aims to ensure successful results in the further study of this vital field.
The chapters in this book thoroughly cover the structure, regulation, and function of matrix metalloproteinases, and provide information on the latest strategies to inhibit enzyme activity. This work will be an indispensable reference tool for investigators with an interest in extracellular matrix biology, matrix turnover, enzymology and biochemistry of proteinases, developmental biology, pathology, and therapeutic interventions. - Provides state-of-the-art information on a field with broad implications to many areas of biology - Includes detailed coverage of the structure and regulation of all major matrix metalloproteinases - Chapters focus on a timely and expanding field - Topics have direct relevance to understanding human disease pathology of cancer, arthritis, and vascular disease - Discusses latest strategies used in the development of new therapeutics to inhibit metalloproteinase activity
The biochemistry and cell biology of Matrix Metalloproteinases (MMPs) are not necessarily straightforward, but basic information on the history of these enzymes, their various functions that extend far beyond the cleaving of the extracellular matrix, and the complex mechanisms that control their expression are valuable to both scientists and clinicians. This volume summarizes the salient features and functions of MMPs and applies this information in a practical manner in order to understand how they contribute to normal physiology and pathology of selected diseases. Chapters by noted clinicians Jean-Michel Dayer, MD in rheumatology, Jian Cao, MD in oncology, and Peter Libby, MD in cardiology, represent important practical and clinically-oriented contributions.
This study covers the sequence information, three-dimensional structures, activation, protein substrates, specificity requirements, inhibition, and biological roles of identified MMPs.
This volume provides new advances regarding the involvement of MMPs in various diseases associated with inflammatory processes. Moreover, the recent development of selective and non selective inhibitors of MMPs give new insights in the relationship between activation of inflammatory cells and tissue remodelling and advise new therapeutics possibilities to the treatment of inflammatory disease. The volume has an international authorship and is written by leading experts in the field.
Matrix metalloproteinases (MMPs) are a family of proteolytic zinc-containing enzymes involved in physiological as well as in pathological processes in the human organism. MMPs play a key role in the remodeling of the extracellular matrix. Such a process may occur because of tissue homeostasis, morphogenesis, and tissue repair. However, remodeling could also be a part of many pathological states such as arthritis, cardiovascular diseases, neurodegenerative diseases, or impaired development in congenital anomalies. This book overviews the role of MMPs in different pathologies affecting the human body.
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.
This detailed volume examines the latest techniques and protocols associated with zymography, the practice of detecting enzyme activity on electrophoretic gels. Sections cover subjects such as endopeptidase zymography, reverse zymography & in situ zymography, 2D zymography, as well as a variety of special cases. Written in the highly respected Methods in Molecular Biology series format, chapters include brief 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. Comprehensive and practical, Zymography: Methods and Protocols serves as an ideal aid for a broad array of researchers from the fields of biological and medicinal science, as well as scientists working in clinical and diagnostic medicine, medical genetics, agricultural entomology, genetic monitoring of environmental pollution, and forensic science.
This volume explores the role of proteases in various catalytic classes and cellular processes associated with cancer. The chapters in this book cover topics such as encoding proteolytic enzymes, cleavage sites of proteases, functional catalytic domains of MMPs, zymography, angiogenesis and lymphangiogenesis, genetic and epigenetic alterations of metallopeptidases, and methods to target metalloproteinases. 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. Comprehensive and cutting edge, Proteases and Cancer: Methods and Protocols is a valuable resource for clinical researchers across numerous fields such as molecular and cellular biology, oncology, biochemistry, and chemistry. This book is also useful for PhD students in the various disciples of health sciences.