Protein Crystallography in Drug Discovery

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.

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.