Discovery of selective, small-molecule inhibitors of RNA complexes--I. The Tat protein/TAR RNA complexes required for HIV-1 transcription
| Autor: | H Y, Mei, D P, Mack, A A, Galan, N S, Halim, A, Heldsinger, J A, Loo, D W, Moreland, K A, Sannes-Lowery, L, Sharmeen, H N, Truong, A W, Czarnik |
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| Rok vydání: | 1997 |
| Předmět: |
Transcriptional Activation
Benzodiazepinones Base Sequence Transcription Genetic Anti-HIV Agents Molecular Sequence Data Virus Replication Antineoplastic Agents Phytogenic Anti-Bacterial Agents Aminoglycosides Gene Products tat HIV-1 Humans RNA Viral Camptothecin Pyrroles tat Gene Products Human Immunodeficiency Virus Amino Acid Sequence HeLa Cells |
| Zdroj: | Bioorganicmedicinal chemistry. 5(6) |
| ISSN: | 0968-0896 |
| Popis: | We have developed a therapeutic program focusing on the inhibition of a human immunodeficiency virus-1 specific protein-RNA interaction. This program begins with a search for small organic molecules that would interfere with the binding of Tat protein to TAR RNA. The methodologies chosen to study the HIV-1 Tat-TAR interaction and inhibition include gel mobility shift assays, scintillation proximity assays, filtration assays, and mass spectrometry. These methods helped establish in vitro high-throughput screening assays which rapidly identified Tat-TAR inhibitors from our corporate compound library. Tat-activated reporter gene assays were then used to investigate the cellular activities of the Tat-TAR inhibitors. The cellular activity, selectivity, and toxicity data for select Tat-TAR inhibitors were determined. Evaluation of both the cellular data and the Tat-TAR inhibition results led to further testing in anti-HIV-1 infection assays. |
| Databáze: | OpenAIRE |
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