Targeted site-specific cleavage of HIV-1 viral Rev responsive element by copper aminoglycosides.
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.
Sreedhara
A
A
Evans Laboratory of Chemistry, The Ohio State University, Columbus 43210, USA.
Cowan
J A
JA
D000617:Aminoglycosides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D003300:Copper; D000242:Cyclic AMP / Q000737:chemistry / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005601:Framycetin / Q000378:metabolism / Q000494:pharmacology; D005814:Genes, Viral; D015752:Genes, env / Q000187:drug effects*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007612:Kanamycin / Q000378:metabolism / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010759:Phosphorus Isotopes; D012360:RNA, Transfer, Phe / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D000617:Aminoglycosides; D010759:Phosphorus Isotopes; D012360:RNA, Transfer, Phe; D005601:Framycetin; D007612:Kanamycin; D003300:Copper; D000242:Cyclic AMP