Current Pharmaceutical Design - Volume 12, Issue 15, 2006

HIV-1 reverse transcriptase (RT) is a multifunctional enzyme that facilitates the conversion of the viral singlestranded (+) RNA genome into double-stranded DNA. The enzyme exhibits both a DNA polymerase activity, that can use either RNA or DNA as a template, and a ribonuclease H (RNase H) activity that specifically degrades the RNA strand of RNA:DNA duplexes. Due to its essential role in the HIV life-cycle, RT is a primary targ Read More

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is an important target of drugs fighting HIV infection. The introduction of potent antiretroviral therapies based on the use of RT inhibitors and/or protease inhibitors has been an important achievement towards the control of AIDS. However, the development of drug resistance constitutes a major hurdle towards long-term efficacy of those therapies. With th Read More

Human immunodeficiency virus type 1 resistance to nucleoside reverse transcriptase inhibitors such as 3'- azido-2', 3'-dideoxythymidine (AZT) can arise through mutations in the coding region of reverse transcriptase (RT) that enhance the enzyme's ability to remove the drug after it has been incorporated. This excision activity of HIV-1 RT has been well characterized in a number of in vitro systems. However, the in vitro finding Read More

While many inhibitors of the Human Immunodeficiency Virus (HIV), the causative agent of Acquired Immunodeficiency Syndrome (AIDS), have been developed, the problem of drug resistance has continued to plague the fight against the disease. The ability of computers to aid in the drug discovery process, and by default the resistance problem, has increased dramatically as the speed of computers and sophistication of a Read More

To date three nonnucleoside reverse transcriptase inhibitors (NNRTIs) have been approved by the U.S. Food and Drug Administration for the treatment of human immunodeficiency virus type 1 infection. A limiting factor in the effectiveness of these agents is the development of resistance, manifested by amino acid substitutions within the virally encoded reverse transcriptase (RT). Understanding the mechanism of action of Read More

A single cycle of nucleotide incorporation by the reverse transcriptase of the human immunodeficiency virus type 1 (HIV-1 RT) involves the initial binding of an incoming nucleotide, a conformational change that traps the substrate, the formation of a new phosphodiester bond, the release of pyrophosphate (PPi), and ultimately polymerase translocation, which clears the nucleotide binding site. This article reviews different mec Read More

Emergence of drug resistant strains of human immunodeficiency virus type 1 (HIV-1) is a major hindrance in the long-term treatment of HIV-1 infected individuals. Alternative strategies, including those directed to structural elements of viral targets, are needed to combat the growing acquired immune deficiency syndrome (AIDS) pandemic. The HIV-1 reverse transcriptase (RT) dimer interface, critical for dimer stability Read More

There is an urgent need for the development of new and safer drugs for the treatment of HIV (human immunodeficiency virus) infection, active against the currently resistant viral strains or directed to novel targets in the viral replicative cycle that may be useful for multiple drug combination. TSAO derivatives are a peculiar group of highly functionalized nucleosides that belong to the so-called nonnucleoside RT in Read More

DNA polymerase and RNase H (RH) activities of HIV reverse transcriptase (RT) have been recognized as potential targets for antiretroviral therapy for more than 15 years. The development of medicines targeting the DNA polymerase activity has been highly successful, with currently 12 drugs approved for the treatment of HIV infection and more candidates in preclinical and clinical development. In contrast, the discovery of po Read More

Prostate cancer (PCa) is the most common cancer for men in Europe, North America, and some parts of Africa. Initially, growth of prostate cancer is usually androgen-dependent, but often it becomes androgen-independent after androgen- deprivation therapy. Managing hormone-refractory prostate carcinoma remains a difficult challenge for clinicians. Retinoids, vitamin A and its synthetic analogs are one of the most studied Read More

The mechanisms of action of anesthetics are unclear. Much attention has been focused on ion channels in the central nervous system as targets for anesthetics. During the last decade, major advances have been made in our understanding of the physiology and pharmacology of G-protein-coupled receptor (GPCR) signaling. Several lines of studies have shown that GPCRs are targets for anesthetics and that some anesthetic Read More