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Human immunodeficiency virus reverse transcriptase : a bench-to-bedside success

Autore: Stuart LeGrice; Matthias Götte
Editore: New York, NY : Springer, 2013.
Edizione/Formato:   eBook : Document : EnglishVedi tutte le edizioni e i formati
Banca dati:WorldCat
Sommario:
The Reverse Transcriptase (RT) of Human Immunodeficiency Virus Type 1 (HIV-1) arguably ranks amongst one of the most extensively studied retroviral enzymes. Heterologous expression and purification of HIV-1 RT in the early eighties, approval of the first nucleoside analogue RT inhibitor (NRTI) in 1987, discovery of resistance to RT inhibitors, approval of the first non-nucleoside analogue RT inhibitor (NNRTI) in  Per saperne di più…
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Dettagli

Genere/forma: Electronic books
Tipo materiale: Document, Risorsa internet
Tipo documento: Internet Resource, Computer File
Tutti gli autori / Collaboratori: Stuart LeGrice; Matthias Götte
ISBN: 9781461472919 1461472911
Numero OCLC: 856550154
Note: Includes index.
Descrizione: 1 online resource (x, 361 pages) : illustrations
Contenuti: Development of the First AIDS Drugs: AZT and Other Dideoxynueosides / Robert Yarchoan, Hiroaki Mitsuya --
Part I: Structure and Function of HIV RT. Proviral DNA Synthesis in HIV: Background / Dorota Piekna-Przybylska Ph.D., Robert A. Bambara Ph.D. --
The RNase H Domain: Structure, Function and Mechanism / Marcin Nowotny, Małgorzata Figiel --
Conformational Dynamics of Reverse Transcription / Stuart F. J. LeGrice --
Part II: Mechanism of Action of Approved RT Inhibitors. Nucleoside RT Inhibitors: Structural and Molecular Biology / Gaofei Lu, Antonio J. Acosta-Hoyos, Walter A. Scott --
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) / Kalyan Das Ph.D., Eddy Arnold Ph.D., Stephen H. Hughes Ph.D. --
Part III: Alternative Strategies to Interfere with the Function of HIV RT. Ribonuclease H Inhibitors: Structural and Molecular Biology / Jason W. Rausch --
Targeting Small Molecules and Peptides to the p66-p51 Reverse Transcriptase Interface / Daouda Abba Moussa, Audrey Agopian, Gilles Divita --
Targeting RT Translocation / Gregory L. Beilhartz, Brian J. Scarth, Matthias Götte --
tRNA Primer Sequestration as an Antiviral Strategy / Christopher P. Jones, Karin Musier-Forsyth --
Part IV: HIV Genetic Variability and the Problem of Drug Resistance. HIV Reverse Transcriptase Fidelity, Clade Diversity, and Acquisition of Drug Resistance / Luis Menéndez-Arias --
APOBECs and Their Role in Proviral DNA Synthesis / John S. Albin, Reuben S. Harris --
Role of RNase H Activity in NRTI/NNRTI Drug Resistance / Gilda Tachedjian B.Sc. (Hons), Ph.D., Nicolas Sluis-Cremer B.Sc. (Hons), Ph.D. --
HIV Population Dynamics / Mary Kearney, John Coffin --
Part V: Prevention and Future Approaches. RT Inhibitors as Microbicides / Jan Balzarini.
Responsabilità: Stuart LeGrice, Matthias Gotte.
Maggiori informazioni:

Abstract:

This book covers coordination of RT-associated DNA polymerase and ribonuclease H activities, mechanisms of action and perspectives on NRTIs and NNRTIs, strategies for targeting the RT enzyme and  Per saperne di più…

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schema:description"The Reverse Transcriptase (RT) of Human Immunodeficiency Virus Type 1 (HIV-1) arguably ranks amongst one of the most extensively studied retroviral enzymes. Heterologous expression and purification of HIV-1 RT in the early eighties, approval of the first nucleoside analogue RT inhibitor (NRTI) in 1987, discovery of resistance to RT inhibitors, approval of the first non-nucleoside analogue RT inhibitor (NNRTI) in 1996 and the various crystal structures of RT with and without bound substrate(s) and/or inhibitors represent only a few of the important milestones that describe the a bench-to-bedside success in the continuing effort to combat HIV-1 infection and its consequences. Nucleoside and nonnucleoside RT inhibitors remain important components in frequently used drug regimens to treat the infection. RT inhibitors also play important roles in recently validated strategies to prevent transmission of the virus. The relevance of HIV-1 RT as a drug target has simultaneously triggered interest in basic research studies aimed at providing a more detailed understanding of interactions between proteins, nucleic acids, and small molecule ligands in general terms. In light of the ever-growing knowledge on structure and function of HIV-1 RT, this enzyme serves as a valuable model system in efforts to develop novel experimental tools and to explain biochemical processes. This monograph is designed to provide an overview of important aspects in past and current HIV-1 RT research, with focus on mechanistic aspects and translation of knowledge into drug discovery and development. The first section includes chapters with emphasis placed on the coordination of the RT-associated DNA polymerase and ribonuclease H (RNase H) activities. The second covers mechanisms of action and future perspectives associated with NRTIs and NNRTIs, while the third section includes chapters focusing on novel strategies to target the RT enzyme. Chapters of the final part are intended to discuss mechanisms involved in HIV variability and the development of drug resistance. We hope that these contributions will stimulate interest, and encourage research aimed at the development of novel RT inhibitors. The lack of bona fide RNase H inhibitors with potent antiviral activity provides an example for challenges and opportunities in the field."
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