| Autor: |
Christophe Pannecouque, Valérie Fargeas, Mickael Montembault, Grant R. Campbell, Erik De Clercq, Vo-Thanh Giang, Myriam Witvrouw, Jean-Marie Peloponese, Jennifer D. Watkins, Jacques Lebreton, Didier Esquieu, James N. Sturgis, Sandrine Opi, Catherine Grégoire, Erwann Loret, Jean de Mareuil, Monique Villiéras, Jean-Pierre Dunot |
| Jazyk: |
angličtina |
| Rok vydání: |
2003 |
| Předmět: |
|
| Zdroj: |
Scopus-Elsevier |
| ISSN: |
0712-4813 |
| DOI: |
10.1155/2003/283731 |
| Popis: |
Tat is a regulatory HIV-1 protein, which has the particularity to be secreted very early by HIV-infected cells. The extra cellular roles of Tat are suspected to be the main cause of the maintenance of reservoirs of HIV-infected cells and the failure of actual AIDS therapies to eradicate HIV. This study describes the rationale used to design molecules that bind to a target area containing an hydrophobic pocket identified in the 2D-NMR structure of Tat. Molecules were synthesized and the derivative named TDS2 was shown to be a Tat inhibitor. Fluorescence revealed that TDS2 binds in the target area, which is conserved across five different Tat variants representative of the main HIV-1 subtypes. TDS2 inhibitedin vitroHIV-1 replication in human T-cells. Further chemical modifications remain necessary to enhance affinity to Tat and reduce cytotoxicity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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