HIV-1 Integrase: Mechanism and Inhibitor Design / Edition 1

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This book comprehensively covers the mechanisms of action and inhibitor design for HIV-1 integrase. It serves as a resource for scientists facing challenging drug design issues and researchers in antiviral drug discovery. Despite numerous review articles and isolated book chapters dealing with HIV-1 integrase, there has not been a single source for those working to devise anti-AIDS drugs against this promising target. But this book fills that gap and offers a valuable introduction to the field for the interdisciplinary scientists who will need to work together to design drugs that target HIV-1 integrase.

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Editorial Reviews

From the Publisher
“This book will be certainly a valuable reference source for all those who are interested in antiviral drug discovery. All of the information contained in this text offers a rich scientific support for researchers in academia and industry at any level who are interested in enhancing their knowledge on a very fascinating scientific topic.”  (ChemMedChem, 2012)
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Product Details

Meet the Author

Nouri Neamati, PhD, is an Associate Professor of Pharmacology and Pharmaceutical Sciences at the University of Southern California School of Pharmacy. He is the recipient of numerous awards and has published more than 170 peer-reviewed manuscripts, several book chapters, and patents in the area of drug design and discovery. Dr. Neamati is the Editor-in-Chief of Current Molecular Pharmacology; an Associate Editor of Current Cancer Drug Targets; and an Editorial Advisory Board member of several journals including Expert Opinion on Drug Discovery, Expert Opinion on Investigational Drugs, and Hormones & Cancer.

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Table of Contents

Chapter 1. HIV life cycle: Targets for anti-HIV agents (Erik De Clercq (Rega Institute)).

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)).

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