Part 2 book “Burger’s medicinal chemistry and drug discovery” has contents: Structure - based drug design, electron cryomicroscopy of biological macromolecules, mass spectrometry and drug discovery, peptidomimetics for drug design, natural products as leads for new pharmaceuticals, and other cotents. | CHAPTER TEN Structure-Based Drug Design LARRY W. HARDY Aurigene Discovery Technologies Lexington, Massachusetts DONALD J. ABRAHAM Virginia Commonwealth University Richmond, Virginia MARTIN K. SAFO Virginia Commonwealth University Richmond, Virginia Contents 1 Introduction, 418 2 Structure-Based Drug Design, 419 Theory and Methods, 419 Hemoglobin, One of the First Drug-Design Targets, 419 History, 419 Sickle-Cell Anemia, 419 Allosteric Effectors, 421 Crosslinking Agents, 424 Antifolate Targets, 425 Dihydrofolate Reductase, 425 Thymidylate Synthase, 426 Structure-Guided Optimization: AG85 and AG337,426 De Novo Lead Generation: AG331,428 Glycinamide Ribonucleotide Formyltransferase, 429 Proteases, 432 Angiotensin-Converting Enzyme and the Discovery of Captopril, 432 HIV Protease, 433 Thrombin, 442 Caspase-1, 444 Matrix Metalloproteases, 445 Oxidoreductases, 446 Inosine Monophosphate Dehydrogenase, 447 Aldose Reductase, 448 Hydrolases, 449 Acetylcholinesterase, 449 Neuraminidase, 450 Burger's Medicinal Chemistry a n d Drug Discovery Sixth Edition, Volume 1: Drug Discovery Edited by Donald J. Abraham ISBN 0-471-27090-3 Q 2003 John Wiley & Sons, Inc. 417 Structure-Based Drug Design Phospholipase A2 (Nonpancreatic, Secretory), 452 Picornavirus Uncoating, 454 Phosphoryl Transferases, 456 1 INTRODUCTION Structure-based drug design by use of structural biology remains one of the most logical and aesthetically pleasing approaches in drug discovery paradigms. The first paper on the potential use of crystallography in medicinal chemistry was written in 1974 (1)and was presented at Professor Alfred Burger's retirement symposium in 1972. The excerpted last paragraph in the paper, reproduced below, foresaw the integration of X-ray crystallography into the field of medicinal chemistry. It is reasonable to assume then that .
