| Autor: |
Sue Yang, Stringner, Pattabiraman, N., Gussio, R., Pallansch, L., Buckheit Jr., R. W., Bader, J. P. |
| Předmět: |
|
| Zdroj: |
Leukemia (08876924); Apr97 Supplement 3, Vol. 11, p89-92, 4p |
| Abstrakt: |
Oxathiin carboxanilide analogs (UC) and αAPA, compounds recognized as nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI), were evaluated for activity against the human immunedeficiency virus (HIV-1) and drug-resistant variants. These NNRTIs are structurally diverse but potent inhibitors of HIV-1 with efficacy in the nanomolar to low micromolar concentrations. They interact at a specific site in the palm domain of the p66 subunit of RT. Treatment of HIV-1 infected cell cultures with UC compounds resulted in the selection of drug-resistant viruses bearing specific amino acid changes at 100, 101, 103, 106, and/or 181, Since Y181C and L1001 are the most commonly observed resistance-engendering mutations, RT enzymatic analysis was correlated with molecular modeling to glean information on the structural interactions between these NNRTIs and RT. Information derived from these studies will facilitate rational drug design and the selection of complementary anti-HIV drugs for combination therapy. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
