Provides the Foundation Needed to Design Effective HIV–1 Integrase Inhibitors
Around the world, scientists have been working for years with the goal of designing effective HIV–1 integrase inhibitors in the battle against AIDS. This book reviews all their latest research findings on both inhibitor design and the mechanisms of action of HIV–1 integrase. Chapters have been contributed by leading pioneers in the field from North America, Europe, and Asia. These contributions represent not only a thorough review of the current literature, but also the authors′ firsthand experience in drug development and design. Coverage includes such topics as:
Integrase mechanism, structure, and function
HIV–1 integrase DNA interaction
Host factors affecting provirus stability and silencing
Role of metals in HIV–1 integrase inhibitor design
Historic perspectives, challenges, and future opportunities
As the first publication to comprehensively examine HIV–1 integrase, this book is essential reading for anyone involved in inhibitor drug discovery.
Integrates chemical, biochemical, and biological approaches, enabling readers to take full advantage of a promising target enzyme for combating HIV and retroviruses
Illustrates rational drug design for a complex drug target with plenty of step–by–step examples
Addresses drug design issues from a variety of perspectives to help readers understand both the challenges and opportunities of developing a successful HIV–1 integrase inhibitor
This book fills an important gap in the review literature, offering a valuable introduction to the field for scientists who need to collaborate with researchers in several disciplines in order to design drugs that effectively target HIV–1 integrase.
Chapter 2. PP32 is hot (Duane P. Grandgenett (SLU)).
Chapter 3. Integrase mechanism and function (Robert Craigie (NIDDK, NIH)).
Chapter 4. Structural studies of retroviral integrases (Mariusz Jaskolski, Jerry N. Alexandratos, Grzegorz Bujacz and Alexander Wlodawer (NIDDK, NCI, NIH)).
Chapter 5. Retroviral integration target site selection (Angela Ciuffi and Frederick Bushman (U. Penn)).
Chapter 6. The pleiotropic nature of human immunodeficiency virus type 1 integrase mutations (Alan Engelman (Harvard)).
Chapter 7. Insights into HIV–1 integrase–DNA interaction (Allison Johnson, Christopse Marchand, and Yves Pommier (NCI, NIH)).
Chapter 8. Functional interaction between human immunodeficiency virus type 1 reverse transcriptase and integrase (Thomas Wilkinson and Samson A. Chow (UCLA)).
Chapter 9. Cellular cofactors of HIV integration (Wannes Thys, Koen Bartholomeeusen, Zeger Debyser and Jan De Rijck (KULeuven)).
Chapter 10. Structural aspects of the lentiviral integrase – LEDGF interaction (Steve Hare, Alan Engelman and Peter Cherepanov (Imperial College London and Harvard)).
Chapter 11. Host factors that affect provirus stability and silencing (Richard A. Katz, René Daniel and Anna Marie Skalka (Fox Chase)).
Chapter 12. Assays for the evaluation of HIV–1 integrase enzymatic activity, DNA–binding and co–factor interaction (Frauke Christ, Katrien Busschots, Jelle Hendrix, Melissa McNeely, Yves Engelborghs, Zeger Debyser (KU Leuven, Belgium)).
Chapter 13. HIV–1 integrase inhibitor design: Overview and historical perspectives (Nouri Neamati (USC)).
Chapter 14. HIV integrase inhibitors: from diketoacids to heterocyclic templates: A history of HIV integrase medicinal chemistry at Merck West Point and Merck Rome (IRBM) leading to the discovery of raltegravir (Melissa S. Egbertson, Neville J. Anthony and Vincenzo Summa).
Chapter 15. Elvitegravir, a novel quinolone HIV–1 integrase strand transfer inhibitor (Hisashi Shinkai, Motohide Sato, and Yuji Matsuzaki, Central Pharmaceutical Research Institute, JT Inc., Takatsuki, Japan).
Chapter 16. Conformationally constrained tricyclic HIV integrase inhibitors (Maria Fardis, Haolun Jin, Xiaowu Chen, Manuel Tsiang, James Chen, Choung Kim, Matthew Wright (Gilead)).
Chapter 17. Slow onset kinetics of HIV integrase inhibitors and proposed molecular model (Edward P. Garvey and Benjamin Schwartz).
Chapter 18. Azaindole hydroxamic acids are hiv–1 integrase inhibitors (Michael B. Plewe, Ted W. Johnson).
Chapter 19. A simple and accurate in vitro method for predicting serum protein binding of hiv integrase strand transfer inhibitors (Ira B. Dicker, Michael A. Walker, Zeyu Lin, Brian Terry, Lori Pajor, Ming Zheng, B. Narasimhulu Naidu, Jacques Banville, Nicholas A. Meanwell and Mark Krystal (BMS)).
Chapter 20. Role of metals in HIV–1 integrase inhibitor design (Mario Sechi, Mauro Carcelli, Dominga Rogolino and Nouri Neamati).
Chapter 21. Discovery and development of natural product inhibitors of HIV–1 integrase (Sheo B. Singh (Merck)).
Chapter 22. Development of styrylquinoline integrase inhibitors (Jean–Francois Mouscadet, Eric Deprez, Didier Desmaele, Jean d′Angelo (CNRS, France)).
Chapter 23. Dicaffeoyltartaric acid and dicaffeoylquinic acid HIV integrase inhibitors (David c. Crosby and W. Edward Robinson, Jr. (UCI)).
Chapter 24. Design and discovery of peptide–based inhibitors (Ya–Qiu Long and Nouri Neamati (Shanghai & USC)).
Chapter 25. Nucleotide–Based Inhibitors of HIV Integrase (Vasu Nair and Guochen Chi (U. Georgia)).
Chapter 26. Design of HIV–1 Integrase Inhibitors Using Computer–aided techniques (Erik Serrao, Rambabu Gundla, Jinxia Deng, Srinivas Odde, Nouri Neamati (USC)).
Chapter 27. Application of protein covalent modification to studying the structure and function of HIV–1 integrase and its inhibitors (Xue Zhi Zhao and Terrence R. Burke, Jr.).
Chapter 28. HIV–1 intergase–DNA models (Chenzhong Liao, Marc C. Nicklaus (NCI)).
Chapter 29. A new paradigm for integrase inhibition: blocking enzyme function without directly targeting the active site (Laith Q. Al–Mawsawi and Nouri Neamati).
Chapter 30. Resistance to integrase inhibitors (Leen Hombrouck, Zeger Debyser and Myriam Witvrouw (KU Leuven, Belgium)).