2003
DOI: 10.1074/jbc.m301749200
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Discovery of a Small Molecule Tat-trans-Activation-responsive RNA Antagonist That Potently Inhibits Human Immunodeficiency Virus-1 Replication

Abstract: Antiretroviral therapy to treat AIDS uses molecules that target the reverse transcriptase and protease enzymes of human immunodeficiency virus, type 1 (HIV-1).A major problem associated with these treatments, however, is the emergence of drug-resistant strains. Thus, there is a compelling need to find drugs against other viral targets. One such target is the interaction between Tat, an HIV-1 regulatory protein essential for viral replication, and trans-activation-responsive (TAR) RNA. Here we describe the desi… Show more

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Cited by 68 publications
(54 citation statements)
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“…It has been established that the TAT protein has a key role in the progression of AIDS and is a potential target for anti-HIV vaccines (4). For the TAT protein to carry out its biological functions, it needs to be readily imported into the cell.…”
mentioning
confidence: 99%
“…It has been established that the TAT protein has a key role in the progression of AIDS and is a potential target for anti-HIV vaccines (4). For the TAT protein to carry out its biological functions, it needs to be readily imported into the cell.…”
mentioning
confidence: 99%
“…Consequently the development and use of antiviral drugs capable of preventing or abrogating HPIV3 infection becomes a strong alternative approach. In the recent past antiviral discovery programs have been initiated towards targeting many pathogenic viruses using various mechanism-based screening methods (Hwang et al, 2003;Mason et al, 2004). Random chemicals and natural product mixtures are being tested for their ability to block replication of a variety of viruses in cell culture systems.…”
Section: Discussionmentioning
confidence: 99%
“…Indeed, on-bead screening with RNA probes have resulted in the identification of ligands for the TAR RNA sequence (Hwang et al, 2003). Similarly, small molecule microarrays might be useful to identify molecules that interact with DNA in a sequence-specific manner.…”
Section: Identification Of Dna Rna and Carbohydrate Ligandsmentioning
confidence: 99%
“…This and related approaches have been used successfully to find peptide ligands for several proteins such as streptavidin (Lam et al, 1991) and the src SH3 domain , ligands for RNAs (Hwang et al, 2003), and peptoid ligands for mdm2 and glutathione S-transferase (Alluri et al, 2003). Up to 1 to 2 million compounds per day can be queried on beads.…”
Section: On-bead Screeningmentioning
confidence: 99%