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Human Immunodeficiency Virus Reverse Transcriptase
Author: Stuart LeGrice
language: en
Publisher: Springer Science & Business Media
Release Date: 2013-07-23
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.
Hydroboration and Organic Synthesis
Author: Ranjit S. Dhillon
language: en
Publisher: Springer Science & Business Media
Release Date: 2007-05-01
This book offers a systematic compilation of the vast data available to synthetic chemists. It provides easy access to the necessary information required for chemical transformations.
HIV I: Molecular Biology and Pathogenesis: Clinical Applications
The cumulative death toll from AIDS has reached 16.3 million individuals, and more than 33 million persons are currently living with HIV-1. Although it is one of the most-widely studied viruses, many mysteries remain about this pathogen. In this comprehensive two-volume set, HIV-1: Molecular Biology and Pathogenesis, leading investigators in HIV research present a timely picture of the molecular mechanisms which guide HIV-1 expression and replication and provide the most current clinical strategies for combating this virus. Twenty-six teams of experts unravel structure-function interactions of HIV-1 with host cells and the resulting pathological consequences, review strategies fo treatment, and describe ongoing progress in developing animal models and prophylactic vaccines.The two volumes, covering viral mechanisms and clinical applications, respectively, are written by an international collection of AIDS expers from North America, Europe, Australia, and Asia. - Detailed insights into viral packaging, expression, and assembly - Mechanistic understanding of how HIV interacts with receptors and infects cells - Delineation of virally encoded regulatory processes unique to HIV - Clinical Applications: - An updated review of current chemotherapeutics for HIV - New concepts in the discovery and design of novel anti-HIV drugs - The latest developments in HIV-vaccine research