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Protein Crystallography in Drug Discovery

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Protein Crystallography in Drug Discovery

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Protein Crystallography in Drug Discovery
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Description

The rational, structure-based approach has become standard in present-day drug design. As a consequence, the availability of high-resolution structures of target proteins is more often than not the basis for an entire drug development program. Protein structures suited for rational drug design are almost exclusively derived from crystallographic studies, and drug developers are relying heavily on the power of this method. Here, researchers from leading pharmaceutical companies present valuable first-hand information, much of it published for the first time. They discuss strategies to derive high-resolution structures for such important target protein classes as kinases or proteases, as well as selected examples of successful protein crystallographic studies. A special section on recent methodological developments, such as for high-throughput crystallography and microcrystallization, is also included. A valuable companion for crystallographers involved in protein structure determination as well as drug developers pursuing the structure-based approach for use in their daily work.

Table of Contents

Preface.A Personal Foreword.List of Contributors.1. Molecular Recognition of Nuclear Hormone Receptor-Ligand Complexes (Robert E. Babine).2. Kinases (Jerry L. Adams, James Veal, and Lisa Shewchuk).3. The Proteasome as a Drug Target (Tsunehiro Mizushima and Tomitake Tsukihara).4. Antibiotics and the Ribosome (Jeffrey L. Hansen).5. Structure-Based Design of Cathepsin K Inhibitors (Daniel F. Veber and Maxwell D. Cummings).6. Structure-Based Design of Potent and Selective Cdk4 Inhibitors (Teruki Honma).7. Crystallization and Analysis of Serine Proteases with Ecotin (Sandra M. Waugh and Robert J. Fletterick).8. X-ray Crystallography in the Development of Orthogonal Ligand-Receptor Pairs (Donald F. Doyle and Lauren J. Schwimmer).9. Engineering Proteins to Promote Crystallization (Lei Jin and Robert E. Babine).10. High-throughput Crystallography (Harren Jhoti).11. Micro-Crystallization (Carl L. Hansen, Morten Sommer, Kyle Self, James M. Berger, and Stephen R. Quake).Subject Index.

Author Biography

Robert E. Babine has diverse drug discovery experience over the past 20 years and is presently the Director of Structural & Computational Chemistry at SPRL in Cambridge, Massachusetts. After receiving his Ph.D. in synthetic organic chemistry at Brown University he joined the medicinal chemistry group at Lederle Laboratories. During his 10 years at Lederle his research evolved into structure-based drug design, culminating in a project that discovered hydroxylaminepentanamide HIV protease inhibitors. Thereafter, he was in the medicinal chemistry group at Agouron Pharmaceuticals where he was involved in the early phase discovery of rhinovirus 3C protease inhibitors. After a 2-year stay at Eli Lilly he joined the new startup company SPRL in 2000. Sherin S. Abdel-Meguid is Chief Scientific Officer and Founder of Suntory Pharmaceutical Research Laboratories (SPRL), a structure-based drug discovery company located in Cambridge, Massachusetts. He joined SPRL from SmithKline Beecham (SB) where he was Director of Macromolecular Sciences and Structural Biology, and director of the IL18, Herpe s virus protease and CD28 programs. Prior to his work for SB, he was Head of Biophysical Sciences and Protein Engineering at Monsanto. At Monsanto, he built one of the first macromolecular crystallography groups in the pharmaceutical industry. He holds a Ph.D. in Physical Chemistry and M.S. and B.S. degrees in Biochemistry.
Release date NZ
January 6th, 2004
Contributors
Edited by Robert E. Babine Edited by Sherin S. Abdel-Meguid Series edited by Gerd Folkers Series edited by Hugo Kubinyi Series edited by Raimund Mannhold
Country of Publication
Germany
Illustrations
illustrations (some col.)
Imprint
Wiley-VCH Verlag GmbH
Pages
278
Dimensions
186x247x19
ISBN-13
9783527306787
Product ID
3080452

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