Lipases and Phospholipases in Drug Development: From Biochemistry to Molecular Pharmacology

Lipases and phospholipases are key control elements in mammalian intermediary metabolism. They share many common features that set them apart from other metabolic enzyme classes, most importantly their association with "two-dimensional" substrates, i. e. lipid droplets, lipoproteins, phospholipid layers, and the resulting implications for their cleavage mechanism and regulation. Their potential as drug targets for the treatment of metabolic diseases is increasingly recognized, and the first lipase inhibitor drugs have been successfully introduced. Providing drug developers with a firm foundation for lipase-centered drug design, the editors of this volume have assembled experts from different scientific disciplines to create a comprehensive handbook for medicinal chemists, structural biologists, biochemists and physiologists interested in lipases. From the contents: Purification of Lipases Physiological and Pathophysiological Roles of Phospholipases in Mammals Phospholipases in Signal Transduction Hormone-sensitive Lipase and Endothelial Lipase as Drug Targets Physiology of Gastrointestinal Lipolysis Therapeutical Use of Lipases and Digestive Lipase Inhibitors Regulation of Triacylglycerol Storage and Mobilization

Table of Contents:
Preface.List of Contributors.1. Purification of Lipase (P. Vasudevan).2. Phospholipase A1: Structures, Physiological and Patho-physiological Roles in Mammals (K. Inoue, et al.). 3. Rational Design of a Liposomal Drug Delivery System Based on Biophysical Studies of Phospholipase A2 Activity on Model Lipid Membranes (K.Jorgensen, et al.). 4. Phospholipase D (J. Exton).5. Sphingomyelinases and Their Interaction with Membrane Lipids (F. Goni & A. Alonso).6. Glycosyl-phosphatidylinositol Cleavage Products in Signal Transduction (Y. Leon & I. Varela-Nieto).7. High-throughput Screening of Hormone-sensitive Lipase and Subsequent Computer-assisted Compound Optimization (S. Petry, et al.). 8. Endothelial Lipase: A Novel Drug Target for HDL and Atherosclerosis? (K. Badellino, et al.). 9. Digestive Lipases Inhibition: an In vitro Study (A. Tiss, et al.). 10. Physiology of Gastrointestinal Lipolysis and Therapeutical Use of Lipases and Digestive Lipase Inhibitors (H. Lengsfeld, et al.). 11. Physiological and Pharmacological Regulation of Triacylglycerol Storage and Mobilization (G. Muller).Subject Index.

About the Author :
Gunter Muller is senior scientist for Biochemistry at Aventis Pharma Germany, Frankfurt am Main, and honorary lecturer for genetics at the University of Munich. He was born in Peissenberg (Germany) and studied anthropology, zoology, genetics and biochemistry at the Ludwig-Maximilians-University in Munich, finishing his PhD thesis under the supervision of R. Zimmermann in 1987. After post-doctoral fellowships at the universities of Ulm and Heidelberg, he joined the pharmaceutical industry in 1990 and received his habilitation at the University of Munich in 1996. He is interested in molecular mechanisms in both lower eukaryotes and mammalian cells, and their use as drug targets for metabolic disorder. Stefan Petry is senior scientist in Medicinal Chemistry at Aventis Germany, Frankfurt am Main. He was born in Kaiserslautern (Germany) and studied Chemistry and Biochemistry at the Albert-Ludwigs-University in Freiburg, including his PhD thesis under the supervision of Jochen Lehmann on photo-affinity labeling of carbohydrate binding proteins. He joined the pharmaceutical industry in 1994. At Aventis he is responsible for projects in the field of diabetes. In particular, he is interested in the development of small molecules which interact with signal transduction processes or influence lipid metabolism.

Review :
"Historical and state-of-the-art information is provided. The international authorship enhances the relevance of the book...the text is well-written and understandable." (E-STREAMS, January 2005)