Proteases of Infectious Agents

Overview

Proteases are enzymes that essentially "eat" protein. Without proteases, infectious organisms cannot properly mount an attack against a host. It is for this reason that proteases have become popular targets for drug discovery. Research has shown that if you can inhibit the protease, you can defend against the invading microbe. The defense against HIV, the virus that causes AIDS, is the best-documented case of the efficacy of protease inhibitors. Researchers are now trying to deploy this strategy against several ...

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Overview

Proteases are enzymes that essentially "eat" protein. Without proteases, infectious organisms cannot properly mount an attack against a host. It is for this reason that proteases have become popular targets for drug discovery. Research has shown that if you can inhibit the protease, you can defend against the invading microbe. The defense against HIV, the virus that causes AIDS, is the best-documented case of the efficacy of protease inhibitors. Researchers are now trying to deploy this strategy against several infectious agents. This book gives information that is useful in that search.
Proteases of Infectious Agents collects reviews from leading experts describing the latest information on the properties of key enzymes from a variety of viruses, fungi, and parasites. Each chapter provides the critical facts needed to initiate a drug discovery effort in that particular area.

Key Features
• Includes information on the basic biology and function of proteases
• Provides global survey of current research efforts in protease inhibitors
• Illustrates how structure-based drug design targets effective and selective compounds
• Highlights important diseases that provide economically important targets
• Describes the role of proteases as important new targets for drug discovery

Audience: Biochemists, microbiologists, structural biophysicists, pharmacologists, and molecular biologists researching and developing therapeutic defenses against infectious agents.

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Editorial Reviews

From The Critics
Reviewer: Mark Kearley, PhD(Creighton University)
Description: This book is a good overview of the structure and inhibition strategies of those proteases which are associated with infectious diseases. Due to the tremendous effort of academic and industrial researchers, the area of protease inhibition is continually evolving but this book is an excellent review of the field up to 1998.
Purpose: The editor's goal is to use protease inhibition as a vehicle for illustrating how the drug discovery process has changed in the past decade. Modern technology now allows us to identify potential drug targets before they are isolated and their structures known. Thus the hunt for potential drugs can begin much sooner than in previous decades. Computer modeling is also a powerful tool for today's drug researchers.
Audience: The editor does not specify an intended audience, but this book would be useful for researchers involved in the field of protease inhibition, biochemists interested in proteases, and medicinal chemists. The writing in this book is quite advanced and thus is not recommended for undergraduates or even first or second year graduate students.
Features: In Chapters 1, 2, and 3, the same general formula is used for presentation: introduction, enzyme structure, substrate specificity, mechanism of action, and inhibitors. This strategy is very logical and makes for an easy read. For various reasons, the remaining chapters do not follow this formula and thus some of them are more difficult to read. Throughout the book, the figures are very helpful, especially those that are in color. In Chapter 1 the inhibition of the HIV protease which is one of the best success stories for this new method of drug discovery is described. However the chapter author does not fully develop the idea of drug discovery. The structures of many HIV protease inhibitors are given (13 pages) but there is not a lot of background information given about them. For example, Saquinavir is a substrate-based inhibitor by Hoffman-LaRoche. It is mentioned in the book for its unique decahydroisoquinoline moiety in the Pl region, but there is no mention of its evolution. Why was a decahydroisoquinoline moiety used? Were there any precursors to Saquinavir or was it a first generation drug? Were computers useful in the design of Saquinavir?
Assessment: This book is a fine overview of protease structure and inhibition. The early chapters are especially well-organized and easy to read, but the entire book is worthwhile. The editor attempts to provide an insight into the changes that have occurred in the field of drug discovery in the past ten years, but in this regard the book falls short.
Mark Kearley
This book is a good overview of the structure and inhibition strategies of those proteases which are associated with infectious diseases. Due to the tremendous effort of academic and industrial researchers, the area of protease inhibition is continually evolving but this book is an excellent review of the field up to 1998. "The editor's goal is to use protease inhibition as a vehicle for illustrating how the drug discovery process has changed in the past decade. Modern technology now allows us to identify potential drug targets before they are isolated and their structures known. Thus the hunt for potential drugs can begin much sooner than in previous decades. Computer modeling is also a powerful tool for today's drug researchers. "The editor does not specify an intended audience, but this book would be useful for researchers involved in the field of protease inhibition, biochemists interested in proteases, and medicinal chemists. The writing in this book is quite advanced and thus is not recommended for undergraduates or even first or second year graduate students. "In Chapters 1, 2, and 3, the same general formula is used for presentation: introduction, enzyme structure, substrate specificity, mechanism of action, and inhibitors. This strategy is very logical and makes for an easy read. For various reasons, the remaining chapters do not follow this formula and thus some of them are more difficult to read. Throughout the book, the figures are very helpful, especially those that are in color. In Chapter 1 the inhibition of the HIV protease which is one of the best success stories for this new method of drug discovery is described. However the chapter author does not fully developthe idea of drug discovery. The structures of many HIV protease inhibitors are given (13 pages) but there is not a lot of background information given about them. For example, Saquinavir is a substrate-based inhibitor by Hoffman-LaRoche. It is mentioned in the book for its unique decahydroisoquinoline moiety in the Pl region, but there is no mention of its evolution. Why was a decahydroisoquinoline moiety used? Were there any precursors to Saquinavir or was it a first generation drug? Were computers useful in the design of Saquinavir? "This book is a fine overview of protease structure and inhibition. The early chapters are especially well-organized and easy to read, but the entire book is worthwhile. The editor attempts to provide an insight into the changes that have occurred in the field of drug discovery in the past ten years, but in this regard the book falls short.

3 Stars from Doody
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Product Details

  • ISBN-13: 9780124205109
  • Publisher: Elsevier Science
  • Publication date: 6/16/1999
  • Edition description: New Edition
  • Edition number: 1
  • Pages: 282
  • Product dimensions: 6.18 (w) x 9.23 (h) x 0.73 (d)

Meet the Author

Ben M. Dunn, Ph.D., is a Distringuished Professor of Biochemistry and Molecular Biology at the University of Florida, Gainesville.

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Table of Contents

J. Erickson and M. Eissenstat, HIV Protease as a Target for the Design of Antiviral Agents for AIDS.
C. Steinkühler, A. Urbani, and R. De Francesco, Proteases of the Hepatitis C Virus.
S. Abdel-Meguid and X. Qiu, Human Herpesvirus Proteases.
C. Abad-Zapatero, R. Goldman, and K. Stewart, The Secreted Proteinases from Candida: Challenges for Structure-Aided Drug Design.
M.N.G. James and E. Bergman, Proteolytic Enzymes of the Viruses of the Family Picornaviridae.
C. Berry, Proteases as Drug Targets in the Treatment of Malaria.
J. Cazzulo, Chagas Disease.
H. Kido, Y. Chen, M. Murakami, Y. Beppu, and T. Towatari, Cellular Proteinases and Viral Infection: Influenza Virus, Sendai Virus, and HIV-1.
M. Lively, Bacterial Type 1 Signal Peptidases.
J.A. Garcia, M.R. Fernández-Fernández, and J.J. López-Moya, Proteinases Involved in Plant Virus Genome Expression.
Subject Index.

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