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

Abstract.

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 tRNA^Phe 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.