Main description:

The book gives students and young researchers a resource on zinc enzymes, some of which were intensively studied for more than six decades and translated into model success stories of the pharmaceutical industry. Up-to-date overviews on the major drug targets of the field are presented, showing the structural basis for catalysis, binding of inhibitors and activators, and their clinical applications. Emergent roles of some recently discovered isozymes in cancer, obesity, epilepsy, pain management, and malaria are also introduced, together with the most recent achievements in drug design from both academia and industry.

Contents:

PREFACE. CONTRIBUTORS. PART I: INTRODUCTION. 1. Introduction to Zinc Enzymes as Drug Targets ( Claudiu T. Supuran and Jean-Yves Winum ). PART II: DRUG DESIGN OF CARBONIC ANHYDRASE INHIBITORS AND ACTIVATORS. 2. Carbonic Anhydrases as Drug Targets: General Presentation ( Claudiu T. Supuran ). 3. Zinc Binding Functions in the Design of Carbonic Anhydrase Inhibitors ( Jean-Yves Winum, Jean-Louis Montero, Andrea Scozzafava, and Claudiu T. Supuran ). 4. X-Ray Crystallography of Carbonic Anhydrase Inhibitors and Its Importance in Drug Design ( Vincenzo Alterio, Anna Di Fiore, Katia D'Ambrosio, Claudiu T. Supuran, and Giuseppina De Simone ). 5. Antiglaucoma Carbonic Anhydrase Inhibitors as Ophthalomologic Drugs ( Francesco Mincione, Andrea Scozzafava, and Claudiu T. Supuran ). 6. Diuretics with Carbonic Anhydrase Inhibitory Activity: Toward Novel Applications for Sulfonamide Drugs ( Daniela Vullo, Alessio Innocenti, and Claudiu T. Supuran ). 7. Drug Design of Carbonic Anhydrase Inhibitors as Anticonvulsant Agents ( Anne Thiry, Jean-Michel Dogn e, Claudiu T. Supuran, and Bernard Masereel ). 8. Carbonic Anhydrase Inhibitors Targeting Cancer: Therapeutic, Immunologic, and Diagnostic Tools Targeting Isoforms IX and XII ( Silvia Pastorekova, Monika Barathova, Juraj Kopacek, and Jaromir Pastorek ). 9. Fluorescent- and Spin-Labeled Sulfonamides as Probe for Carbonic Anhydrase IX ( Alessandro Cecchi, Laura Ciani, Sandra Ristori, and Claudiu T. Supuran ). 10. Drug Design of Antiobesity Carbonic Anhydrase Inhibitors ( Giuseppina De Simone and Claudiu T. Supuran ). 11. Dual Carbonic Anhydrase and Cyclooxygenase-2 Inhibition ( Jean-Michel Dogn e, Anne Thiry, Bernard Masereel, and Claudiu T. Supuran ). 12. Advances in the Inhibitory and Structural Investigations on Carbonic Anhydrase Isozymes XIII and XV ( Mika Hilvo, Giuseppina De Simone, Claudiu T. Supuran, and Seppo Parkkila ). 13. Mechanism and Inhibition of the b-Class and c-Class Carbonic Anhydrases (James G. Ferry and Claudiu T. Supuran ). 14. Fungal and Nematode Carbonic Anhydrases: Their Inhibition in Drug Design ( Rebecca A. Hall and Fritz. A. MEURO uhlschlegel ). 15. Crystallographic Studies on Carbonic Anhydrases from Fungal Pathogens for Structure-Assisted Drug Development ( Uta-Maria Ohndorf, Christine Schlicker, and Clemens Steegborn ). 16. Malaria Parasite Carbonic Anhydrase and Its Inhibition in the Development of Novel Therapies of Malaria ( Jerapan Krungkrai, Sudaratana R. Krungkrai, and Claudiu T. Supuran ). 17. Inhibitors of Helicobacter pylori a- and b-Carbonic Anhydrases as Novel Drugs for Gastroduodenal Diseases ( Isao Nishimori, Hiroaki Takeuchi, and Claudiu T. Supuran ). 18. QSAR of Carbonic Anhydrase Inhibitors and Their Impact on Drug Design ( Adriano Martinelli and Tiziano Tuccinardi ). 19. Selectivity Issues in the Design of CA Inhibitors ( Claudiu T. Supuran and Jean-Yves Winum ). 20. Bicarbonate Transport Metabolons ( Danielle E. Johnson and Joseph R. Casey ). 21. Metal Complexes of Sulfonamides as Dual Carbonic Anhydrase Inhibitors ( Marc A. Ilies ). 22. Drug Design Studies of Carbonic Anhydrase Activators ( Claudia Temperini, Andrea Scozzafava, and Claudiu T. Supuran ). PART III DRUG DESIGN OF MATRIX METALLOPROTEINASE INHIBITORS. 23. Matrix Metalloproteinases: An Overview ( Hideaki Nagase and Robert Visse ). 24. MMP Inhibitors Based on Earlier Succinimide Strategies: From Early to New Approaches ( M. Amelia Santos ). 25. Drug Design of Sulfonylated MMP Inhibitors ( Armando Rossello and Elisa Nuti ). 26. ADAMs and ADAMTs Selective Synthetic Inhibitors ( Armando Rossello, Elisa Nuti, and Alfonso Maresca ). 27. QSAR Studies of MMP Inhibitors ( Tiziano Tuccinardi and Adriano Martinelli ). PART IV DRUG DESIGN OF BACTERIAL ZINC PROTEASE INHIBITORS. 28. Bacterial Zinc Proteases as Orphan Targets ( Claudiu T. Supuran ). 29. Botulinus Toxin, Tetanus Toxin, and Anthrax Lethal Factor Inhibitors ( Antonio Mastrolorenzo and Claudiu T. Supuran ). 30. Clostridium histolyticum Collagenase Inhibitors in the Drug Design ( Claudiu T. Supuran ). 31. Other Bacterial Zinc Peptidases as Potential Drug Targets ( Kunihiko Watanabe ). PART V DRUG DESIGN STUDIES OF OTHER ZINC-CONTAINING ENZYMES. 32. Angiotensin Converting Enzyme (ACE) Inhibitors ( Ana Camara-Artigas, Vicente Jara-Perez, and Montserrat Andujar-S anchez ). 33. P-III Metalloproteinase (Leucurolysin-B) from Bothrops leucurus Venom: Isolation and Possible Inhibition ( Eladio F. Sanchez and Johannes A. Eble ). 34. CaaX-Protein Prenyltransferase Inhibitors ( Martin Schlitzer, Regina Ortmann, and Mirko Altenk amper ). 35. Histone Deacetylase Inhibitors ( Paul W. Finn ). 36. Recent Development of Diagnostic and Therapeutic Agents Targeting Glutamate Carboxypeptidase II (GCPII) ( Youngjoo Byun, Ronnie C. Mease, Shawn E. Lupold, and Martin G. Pomper ). 37. Targeting HIV-1 Integrase Zinc Binding Motif ( Mario Sechi, Mauro Carcelli, Dominga Rogolino, and Nouri Neamati ). 38. Inhibitors of Histidinol Dehydrogenases as Antibacterial Agents ( Pascale Joseph, Franccois Turtaut, Stephan KEURO ohler, and Jean-Yves Winum ). 39. Dihydroorotase Inhibitors ( Mihwa Lee, Megan J. Maher, Richard I. Christopherson, and J. Mitchell Guss ). 40. APOBEC3G: A Promising Antiviral Target ( Claudiu T. Supuran and Jean-Yves Winum ). Index.