Targeted site-specific cleavage of HIV-1 viral Rev responsive element by copper aminoglycosides

被引:0
作者
Alavattam Sreedhara
J.A. Cowan
机构
[1] Evans Laboratory of Chemistry,
[2] The Ohio State University,undefined
[3] 100 West 18th Avenue,undefined
[4] Columbus,undefined
[5] OH 43210,undefined
[6] USA,undefined
[7] Present address: Molecular,undefined
[8] Cellular and Developmental Biology,undefined
[9] Yale University,undefined
[10] 219 Prospect Street,undefined
[11] New Haven,undefined
[12] CT 06520,undefined
[13] USA,undefined
来源
JBIC Journal of Biological Inorganic Chemistry | 2001年 / 6卷
关键词
HIV Rev response element RNA Cleavage Aminoglycoside Drug target Copper;
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学科分类号
摘要
Site-specific cleavage of the HIV-1 viral Rev responsive element by copper aminoglycosides is reported under physiological conditions. This bubble and stem-loop RNA structure is efficiently targeted at micromolar concentrations of complex. The specificity of cleavage of structured viral RNA relative to a non-cognate tRNAPhe of well-defined secondary and tertiary structure is demonstrated. Cleavage products from simpler substrates [diribonucleotide (ApA) and 2′,3′-cyclic monophosphate ester (cAMP)] were analyzed by 31P NMR and demonstrate a hydrolytic mechanism in the absence of external redox agents. These results demonstrate copper aminoglycosides to be highly efficient chemical nucleases with a targeting capability for viral RNA and suggest a novel methodology to counter RNA viruses.
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页码:166 / 172
页数:6
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