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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.

HIV (Viruses) --- Reverse transcriptase --- RNA-Directed DNA Polymerase --- DNA-Directed DNA Polymerase --- DNA Nucleotidyltransferases --- Nucleotidyltransferases --- Phosphotransferases --- Transferases --- Enzymes --- Enzymes and Coenzymes --- Chemicals and Drugs --- HIV Reverse Transcriptase --- Biology --- Health & Biological Sciences --- Microbiology & Immunology --- Immunology. --- HIV infections --- Research --- Methodology. --- HIV (Viruses) infections --- HTLV-III infections --- HTLV-III-LAV infections --- Human T-lymphotropic virus III infections --- Immunobiology --- Medicine. --- Virology. --- Infectious diseases. --- Biomedicine. --- Infectious Diseases. --- Life sciences --- Serology --- Lentivirus infections --- Sexually transmitted diseases --- Medical virology. --- Emerging infectious diseases. --- Medical microbiology --- Virology --- Virus diseases --- Emerging infections --- New infectious diseases --- Re-emerging infectious diseases --- Reemerging infectious diseases --- Communicable diseases --- Microbiology

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DNA-Directed DNA Polymerase --- DNA-Directed RNA Polymerases --- Enzyme Inhibitors. --- Antibiotics --- -DNA polymerases --- -RNA polymerases --- -DNA-dependent RNA polymerases --- DNA-directed RNA polymerases --- Polymerases, RNA --- Ribonucleate nucleotidyltransferases --- RNA nucleotidyltransferases --- Transferases --- Deoxyribonucleate nucleotidyltransferases --- DNA-dependent DNA polymerases --- DNA-directed DNA polymerases --- DNA nucleotidyltransferases --- Nucleotidyltransferases, Deoxyribonucleate --- Polymerases, DNA --- Zinc enzymes --- Polymerase chain reaction --- Anti-infective agents --- Microbial metabolites --- Allelopathic agents --- Antibiosis --- Pharmaceutical microbiology --- Phytoncides --- Inhibitors, Enzyme --- Enzymes --- Sulfhydryl Reagents --- antagonists & inhibitors. --- Physiological effect --- -Congresses --- Inhibitors --- antagonists & inhibitors --- -antagonists & inhibitors. --- DNA polymerases --- RNA polymerases --- Congresses. --- Enzyme Inhibitors --- DNA-dependent RNA polymerases --- Physiological effect&delete& --- Congresses --- Inhibitors&delete& --- Enzyme Inhibitor --- Inhibitor, Enzyme --- DNA Polymerase Inhibitors --- Inhibitors, DNA Synthesis --- Inhibitors, Nucleic Acid Synthesis --- Inhibitors, RNA Synthesis --- DNA Polymerase Inhibitor --- DNA Synthesis Inhibitor --- DNA Synthesis Inhibitors --- Nucleic Acid Synthesis Inhibitor --- RNA Synthesis Inhibitor --- RNA Synthesis Inhibitors --- Inhibitor, DNA Polymerase --- Inhibitor, DNA Synthesis --- Inhibitor, RNA Synthesis --- Inhibitors, DNA Polymerase --- Polymerase Inhibitor, DNA --- Polymerase Inhibitors, DNA --- Synthesis Inhibitor, DNA --- Synthesis Inhibitor, RNA --- Synthesis Inhibitors, DNA --- Synthesis Inhibitors, RNA --- DNA --- RNA --- ENZYME INHIBITORS --- CHEMICAL SYNTHESIS

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The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with more than 300 volumes (all of them still in print), the series contains much material still relevant today-truly an essential publication for researchers in all fields of life sciences.This volume and its companions (Volumes 330 and 331) cover all current knowledge concern

Proteolytic enzymes. --- DNA --- Enzyme Stability --- Enzymes --- Pyrococcus furiosus --- Pyrococcus --- Enzymes and Coenzymes --- Technology, Pharmaceutical --- Protein Stability --- Nucleic Acids --- Nucleic Acids, Nucleotides, and Nucleosides --- Thermococcaceae --- Biochemical Phenomena --- Chemicals and Drugs --- Investigative Techniques --- Chemical Phenomena --- Thermococcales --- Analytical, Diagnostic and Therapeutic Techniques and Equipment --- Phenomena and Processes --- Euryarchaeota --- Archaea --- Organisms --- Animal Biochemistry --- Human Anatomy & Physiology --- Health & Biological Sciences --- Temperature --- Hydrolases --- Weather --- Atmosphere --- Thermodynamics --- Meteorological Concepts --- Physical Phenomena --- Ecological and Environmental Phenomena --- Environment --- Biological Phenomena --- Environment and Public Health --- Health Care --- Bacteria --- Hot Temperature --- Peptide Hydrolases --- Archaea. --- Biochemistry -- Periodicals. --- Biochemistry. --- Enzymes -- Periodicals. --- Enzymes. --- Microorganisms. --- Glycoside Hydrolases --- Adaptation, Physiological --- Physiological Processes --- Adaptation, Biological --- Physiological Phenomena --- Biological Processes --- Microorganisms --- Effect of heat on. --- Effect of temperature on. --- Esteroproteases --- Peptidases --- Proteases --- Proteinases --- Proteolytic Enzymes --- Heat --- Hot Temperatures --- Temperature, Hot --- Temperatures, Hot --- Eubacteria --- Community-Based Distribution --- Contraceptive Distribution --- Delivery of Healthcare --- Dental Care Delivery --- Distribution, Non-Clinical --- Distribution, Nonclinical --- Distributional Activities --- Healthcare --- Healthcare Delivery --- Healthcare Systems --- Non-Clinical Distribution --- Nonclinical Distribution --- Delivery of Dental Care --- Health Care Delivery --- Health Care Systems --- Activities, Distributional --- Activity, Distributional --- Care, Health --- Community Based Distribution --- Community-Based Distributions --- Contraceptive Distributions --- Deliveries, Healthcare --- Delivery, Dental Care --- Delivery, Health Care --- Delivery, Healthcare --- Distribution, Community-Based --- Distribution, Contraceptive --- Distribution, Non Clinical --- Distributional Activity --- Distributions, Community-Based --- Distributions, Contraceptive --- Distributions, Non-Clinical --- Distributions, Nonclinical --- Health Care System --- Healthcare Deliveries --- Healthcare System --- Non Clinical Distribution --- Non-Clinical Distributions --- Nonclinical Distributions --- System, Health Care --- System, Healthcare --- Systems, Health Care --- Systems, Healthcare --- Biologic Phenomena --- Biological Phenomenon --- Biological Process --- Phenomena, Biological --- Phenomena, Biologic --- Phenomenon, Biological --- Process, Biological --- Processes, Biological --- Environmental Impact --- Environmental Impacts --- Impact, Environmental --- Impacts, Environmental --- Environments --- Meteorologic Factors --- Meteorological Factors --- Concept, Meteorological --- Concepts, Meteorological --- Factor, Meteorologic --- Factor, Meteorological --- Factors, Meteorologic --- Factors, Meteorological --- Meteorologic Factor --- Meteorological Concept --- Meteorological Factor --- Biocatalysts --- Thermodynamic --- Ecological and Environmental Concepts --- Ecological and Environmental Processes --- Atmospheres --- Fog --- Fogs --- Temperatures --- Physical Phenomenon --- Physical Process --- Physical Concepts --- Physical Processes --- Concept, Physical --- Concepts, Physical --- Phenomena, Physical --- Phenomenon, Physical --- Physical Concept --- Process, Physical --- Processes, Physical --- Coenzymes and Enzymes --- Peptide hydrolases --- Micro-organisms, Effect of temperature on --- Ferments --- Soluble ferments --- Catalysts --- Proteins --- Enzymology --- Physiological effect --- ARCHAEA --- HEAT --- ENZYMES --- BIOLOGICAL EFFECTS --- Dna nucleotidyltransferases --- Isomerases --- Oxidoreductases --- Temperature effects (biological)