We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Discovery of a Tat HIV-1 inhibitor through computer-aided drug design.
- Authors
Esquieua, Didier; Péloponèse, Jean-Marie; Opi, Sandrine; Gregoire, Catherine; Mareuil, Jean de; Watkins, Jennifer; Campbell, Grant; Dunot, Jean-Pierre; Sturgis, James; Witvrouw, Myriam; Pannecouque, Christophe; Montembault, Mickaël; Giang, Vo-Thanh; Villiéras, Monique; Lebreton, Jacques; Loret, Erwann P.; de Clercq, Erik; Fargeas, Valérie
- Abstract
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 he 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 hind 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 he 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 inhibited in vitro HIV-1 replication in human T-cells. Further chemical modifications remain necessary to enhance affinity to Tat and reduce cytotoxicity.
- Subjects
AIDS treatment; HIV infections; CELL-mediated cytotoxicity; DRUG development; VIRAL replication; COMPUTER-aided design; T cells
- Publication
Spectroscopy: An International Journal, 2003, Vol 17, Issue 4, p639
- ISSN
0712-4813
- Publication type
Article
- DOI
10.1155/2003/283731