The Chemical Biology of Thrombin

by Roger L. Lundblad

Overview

This book is a comprehensive review of thrombin, especially as regulatory protease. The ready availability of highly purified thrombin has stimulated rapid advances in the cell biology of this important macromolecule. The text focuses on research findings from the discovery of thrombin by Andrew Buchanan in 1842 to the present. A substantial amount of this work was conducted by the author and his colleagues. His work on the purification of thrombin was seminal to much subsequent work on thrombin. This volume provides a framework for future studies now made possible by the discovery of the importance of exosites in the physiology of thrombin function. The current work describes the process of the development of an oral inhibitor of thrombin used in the prevention of thrombosis.

Key Features

• Reviews the history of Thrombin (Fibrin Ferment)
• Documents the relation of protein engineering and chemical modification in the study of thrombin
• Summarizes the interaction of thrombin with fibrinogen and fibrin
• Outlines the role of exosites in thrombin function
• Describes the development of an oral inhibitor for thrombin

Product Details

ISBN-13:	9781032203300
Publisher:	CRC Press
Publication date:	01/29/2024
Pages:	284
Product dimensions:	6.12(w) x 9.19(h) x (d)

About the Author

Roger L. Lundblad is an independent consultant based in Chapel Hill, North Carolina. He is also an adjunct professor of pathology at the University of North Carolina, Chapel Hill.

Table of Contents

Preface. Acknowledgements. About the Author. The History of Thrombin. The Formation of Thrombin. Structural Biology of Thrombin. The Use of Protein Engineering (Mutagenesis) to Study Functional Regions in Thrombin Expression and Characterization of Recombinant Thrombins. Chemical Modification of Thrombin. The Interaction of Thrombin with Fibrinogen and Fibrin. Thrombin and Platelets. Inhibitors of Thrombin. Index.

Editorial Reviews

Reviewer: Peter J. Kennelly, PhD (Virginia Tech)
Description: Thrombin is the terminal protease in a series of proteolytic enzymes referred to as the blood coagulation cascade. Its purpose is to catalyze the rapid, localized formation of the first step in blood coagulation — the formation of the fibrin net. Thrombin is also the target of many therapeutic agents, including so-called blood thinners such as heparin, dabigatran etexilate, and argatroban, designed to prevent or reduce the formation of blood clots in patients suffering from cardiac or circulatory injury or disease.
Purpose: The book provides "a comprehensive review of thrombin, its role in blood coagulation, and the development of oral inhibitors of thrombin." The book emphasizes the author's own work on purifying thrombin as well as the importance of exosites, ligand biding sites that must be occupied in order to render an enzyme catalytically active, in the physiology of thrombin function.
Audience: The book is well suited for a general biomedical audience ranging from curious undergraduates to expert principal investigators.
Features: The author provides a rich, personal historical perspective that begins with the seminal work on the identification and characterization of thrombin performed by Andrew Buchanan in the 1830s and 40s. The more contemporary parts of this history are enlivened by the inclusion of personal observations drawn from the author's 50 years of experience in thrombin research. At times, the emphasis on historical perspective emerges as a double-edged sword. More often than not, the clearest and most straightforward description of a complex biomolecular process rarely adheres to the chronological narrative. Too many paragraphs offer little more than a chronological list of published observations with little or no context or explanation of their significance. On the other hand, persons wishing to explore the primary literature of thrombin will find this book to be a rich, comprehensive source of historical references. Lastly, with the exception of the many chemical structures portrayed in the chapter on thrombin inhibitors, disappointingly little use is made of illustrations and other types of figures to amplify, clarify, and visually break up the rather densely packed text.
Assessment: As befitting its important status on blood coagulation and thrombosis, books devoted to thrombin appear on a fairly regular basis. However, the majority of these are devoted to the physiology of the heart and circulatory system, including the impact of disease and injury, and clinical interventions. Few offer either the historic depth or detailed focus on the exploration of structure-function relationships or the development of therapeutic inhibitors that characterize this book. While the book would have benefited from a more aggressive use of illustrations, and although the frequent excursions by the author into the first person can be distracting, on the whole, this book represents a unique, informative, and readable addition to a biomedical library.

Doody's Review Service