共 18 条
Blocking HIV replication by targeting Tat protein
被引:31
作者:

Hamy, F
论文数: 0 引用数: 0
h-index: 0
机构: Univ Basel, Inst Med Microbiol, CH-4003 Basel, Switzerland

Gelus, N
论文数: 0 引用数: 0
h-index: 0
机构: Univ Basel, Inst Med Microbiol, CH-4003 Basel, Switzerland

Zeller, M
论文数: 0 引用数: 0
h-index: 0
机构: Univ Basel, Inst Med Microbiol, CH-4003 Basel, Switzerland

Lazdins, JL
论文数: 0 引用数: 0
h-index: 0
机构: Univ Basel, Inst Med Microbiol, CH-4003 Basel, Switzerland

Bailly, C
论文数: 0 引用数: 0
h-index: 0
机构: Univ Basel, Inst Med Microbiol, CH-4003 Basel, Switzerland

Klimkait, T
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Basel, Inst Med Microbiol, CH-4003 Basel, Switzerland Univ Basel, Inst Med Microbiol, CH-4003 Basel, Switzerland
机构:
[1] Univ Basel, Inst Med Microbiol, CH-4003 Basel, Switzerland
[2] Novartis Pharma Res, CH-4002 Basel, Switzerland
[3] INSERM Unite 524, F-59045 Lille, France
[4] Solvias AG, CH-4002 Basel, Switzerland
来源:
CHEMISTRY & BIOLOGY
|
2000年
/
7卷
/
09期
关键词:
CXCR4;
coreceptor;
HIV infection;
Tat inhibition;
D O I:
10.1016/S1074-5521(00)00012-0
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Background: A rapid development of viral drug resistance poses a serious limitation in the current drug development programs against HIV. In turn, this obstacle forms the basis for new efforts. which utilize alternative viral targets. Results: By aiming at the Tat-driven process of HIV gene regulation, we discovered a new class of compounds as well as a novel target. The candidate compound acts on the one hand by classically inhibiting Tat/TAR complexation, however, without binding to nucleic acids. Conclusions: Structure and molecular modeling/dynamics suggest that the stilbene derivative CGA137053 directly binds to Tat protein but not TAR RNA. As a completely new, second property, the compound also antagonizes a TAR-independent activity of free Tat protein by preventing the recently described upregulation of the HIV coreceptor CXCR4. With the stilbene CGA137053, we have identified a potent, double-hitting and chemically feasible Tat antagonist. The compound possesses high target specificity and low cytotoxicity, is not restricted to the Tat/TAR axis of HIV inhibition and highly active on HIV-infected, primary human cells.
引用
收藏
页码:669 / 676
页数:8
相关论文
共 18 条
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KLIMKAIT, T
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CIBA GEIGY AG,DIV PHARMACEUT,ONCOL & VIROL RES DEPT,K125308,CH-4002 BASEL,SWITZERLAND CIBA GEIGY AG,DIV PHARMACEUT,ONCOL & VIROL RES DEPT,K125308,CH-4002 BASEL,SWITZERLAND

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CIBA GEIGY AG,DIV PHARMACEUT,ONCOL & VIROL RES DEPT,K125308,CH-4002 BASEL,SWITZERLAND CIBA GEIGY AG,DIV PHARMACEUT,ONCOL & VIROL RES DEPT,K125308,CH-4002 BASEL,SWITZERLAND

ROESEL, JL
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CIBA GEIGY AG,DIV PHARMACEUT,ONCOL & VIROL RES DEPT,K125308,CH-4002 BASEL,SWITZERLAND CIBA GEIGY AG,DIV PHARMACEUT,ONCOL & VIROL RES DEPT,K125308,CH-4002 BASEL,SWITZERLAND

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SLIM, G
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BUTLER, PJG
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KARN, J
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GAIT, MJ
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