SELECTIVE RECOGNITION AND CLEAVAGE OF RNA LOOP STRUCTURES BY NI(II)CENTER-DOT-XAA-GLY-HIS METALLOPEPTIDES

The recognition and cleavage of tRNA(Phe) and the TAR RNA of HIV-1 by metallopeptides of the general form Ni(II). Xaa-Gly-His (where Xaa is Gly, Lys, or Arg) were investigated. The results of RNA cleavage analy ses suggest that KHSO5- or magnesium monoperoxyphthalate-activated met allopeptides (1) induce nucleobase damage which requires aniline aceta te for complete RNA strand scission and (2) selectively target the loo ps of stem-loop structures of the above-named substrates. In targeting RNA loop regions, the metallopeptides may be sensitive to intraloop s tructural features, including the overall structural environment of th e loop itself and possibly the presence of intraloop hydrogen bonding. Overall, these results suggest that the metallopeptides interact sele ctively within a loop, in a fashion reminiscent of many RNA binding pr oteins, instead of targeting RNA single-stranded character alone. Thes e observations further suggest a possible metallopeptide-based strateg y for the molecular recognition of native RNA structures and insight w ith regard to the general features available for ligand binding site d iscrimination.