Proteinase and Peptidase Inhibition

Overview

Cellular proteinases and their physiological role in normal and disease states have been the subject of great interest over recent decades. At present, specific protease inhibitors are exploited both as tools in unraveling the role of individual proteinases in particular cellular processes and for the development of chemotherapeutic agents for the treatment of various disorders. Proteinase and Peptidase Inhibition presents updated progress reports on the characterization of a wide range of cellular proteinases ...

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Overview

Cellular proteinases and their physiological role in normal and disease states have been the subject of great interest over recent decades. At present, specific protease inhibitors are exploited both as tools in unraveling the role of individual proteinases in particular cellular processes and for the development of chemotherapeutic agents for the treatment of various disorders. Proteinase and Peptidase Inhibition presents updated progress reports on the characterization of a wide range of cellular proteinases whose inhibitors may hold the key to the development of new drugs. Introductory chapters deal with the broad enzyme classes, inhibitor types and regulatory mechanisms governing proteinase activity. The target enzymes themselves, together with all aspects of their inhibition and inhibitor design, are comprehensively described. The classification of target enzymes by structural similarity, rather than by pharmacological effects, provides a new and coherent platform for understanding how inhibition of different targets can lead to the same therapeutic outcomes. This is a valuable reference book that will appeal to both academic and industrial researchers in the fields of medicinal chemistry, drug design and development, pharmacology, biochemistry, and molecular and cell biology.

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Editorial Reviews

Doody's Review Service
Reviewer: Alan Poisner, MD (University of Kansas Medical Center)
Description: This book describes a group of mammalian and non-mammalian peptidases and their inhibitors with proven and yet to be proven utility as therapeutic agents. The structural mechanisms that underly inhibitory activity are emphasized. Two introductory chapters on classes, mechanisms, and regulation provide some overview that is pertinent to more than one set of agents.
Purpose: The editors seek to stimulate the development of protease inhibitors that could be of therapeutic utility in common diseases. The book is essentially a "state-of-the-art" review as of late 2001 of the clinical use and needs for a selected group of protease inhibitors. For the most part, the book meets the editors' objectives. The biological and pharmacokinetic problems in this field are not emphasized.
Audience: "The book is intended to spur development of new agents and thus is aimed at medicinal chemists and pharmaceutical chemists. The material would also be of interest to biochemists, pharmacologists, and students interested in the clinical use of protease inhibitors. Since each chapter is very specific, individuals working in selected areas may not be interested in all of the chapters. The chapter authors appear to be credible authorities on the enzymes. Their orientation appears to be more chemical than biological. "
Features: "The enzymes and inhibitors are grouped according to the types of catalytic activity rather than by disease or biological function. This allows a thorough discussion on structure and mechanisms. The black-and-white and color photos are well suited for this objective. The color photos help in understanding structural details. Some authors appear to oversimplify the biological background of their subject and this includes incomplete references. The first chapter on nomenclature provides the current recognized terminology, but the editors and a number of authors frequently choose to ignore it. There are some errors (page 309: "In the blood clotting cascade, aminopeptidase A appears to liberate angiotensin from angiotensin II (Chavuvel et al. 1994)."). Chapter 16 has an incomplete and thus misleading biochemical pathway for angiotensin-I metabolism. This chapter also omits reference to chymase in the production of angiotensin II (and hence a target for ACE resistance) and the potential relevance of angiotensin (1-7) in the hypotensive (and other) effects of ACE inhibitors. This appears to be due to the authors' background. It might have helped to have an overview chapter on the pharmacokinetic limitations of protease inhibitors. "
Assessment: "As in any multiauthored book, this one shows a wide variation in quality and orientation in the various chapters. It should appeal to medicinal and pharmaceutical chemists with an interest in specific enzyme targets. Information on the structural features of these enzymes and inhibitors ultimately must be complemented by more detailed analysis of the biological problems associated with the use of enzyme inhibitors as therapeutic agents. "

3 Stars from Doody
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Product Details

  • ISBN-13: 9780415273497
  • Publisher: CRC Press
  • Publication date: 3/31/2002
  • Pages: 440
  • Product dimensions: 7.10 (w) x 10.00 (h) x 0.96 (d)

Table of Contents

Enzyme Classes and Mechanisms. Regulatory Mechanisms for Proteinase Activity. Matrix Metalloproteinases (MMPs). Proteasomes. Cathepsins. Calpain. Human Neutrophil Elastase Inhibitors. Thrombin. Inhibitors of Factor VIIa, Factor IXa, and Factor Xa as Anticoagulants. The Urokinase-Type Plasminogen Activator (uPA) System: A New Target for Tumor Therapy. Proteinases Involved in Amyloid ß-Peptide (Aß) Production and Clearance. Herpes Virus and Cytomegalovirus Proteinase. Human Rhinovirus 3C Proteinase Inhibitors. Aminopeptidases. The Hepatitis C Virus NS3 Serine-Type Proteinase. Zinc Metallopeptidases. HIV Aspartate Proteinase: Resistance to Inhibitors. Proteases of Protozoan Parasites for Proteinase Activity.

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