Screen LibraryHuman immunodeficiency virus reverse transcriptase : a bench-to-bedside success /
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 19...
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| Corporate Authors: | |
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| Group Author: | ; |
| Published: |
Springer,
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| Publisher Address: | New York, NY : |
| Publication Dates: | 2013. |
| Literature type: | eBook |
| Language: | English |
| Subjects: | |
| Online Access: |
http://dx.doi.org/10.1007/978-1-4614-7291-9 |
| Summary: |
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 mechanism |
| Item Description: | Includes index. |
| Carrier Form: | 1 online resource (x, 361 pages) : illustrations |
| ISBN: |
9781461472919 (electronic bk.) 1461472911 (electronic bk.) |
| Index Number: | QR201 |
| CLC: | R512.91 |
| Contents: |
Development of the First AIDS Drugs: AZT and Other Dideoxynueosides / Structure and Function of HIV RT. Proviral DNA Synthesis in HIV: Background / The RNase H Domain: Structure, Function and Mechanism / Conformational Dynamics of Reverse Transcription / Mechanism of Action of Approved RT Inhibitors. Nucleoside RT Inhibitors: Structural and Molecular Biology / Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) / Alternative Strategies to Interfere with the Function of HIV RT. Ribonuclease H Inhibitors: Structural and Molecular Biology / Targeting Small Molecules and Peptides to the p66-p51 Reverse Transcriptase Interface / Targeting RT Translocation / tRNA Primer Sequestration as an Antiviral Strategy / HIV Genetic Variability and the Problem of Drug Resistance. HIV Reverse Transcriptase Fidelity, Clade Diversity, and Acquisition of Drug Resistance / APOBECs and Their Role in Proviral DNA Synthesis / Role of RNase H Activity in NRTI/NNRTI Drug Resistance / HIV Population Dynamics / Prevention and Future Approaches. RT Inhibitors as Microbicides / |