The Role of Lead(II) in Nucleic Acids

Although lead(II) is naturally not associated with nucleic acids, this metal ions has been applied with DNA and RNA in various contexts. Pb2+ is an excellent hydrolytic metal ion for nucleic acids, which is why it is mainly used as probing agent for secondary structure and to determine metal ion binding sites both in vitro and in vivo. A further application of lead(II) is in structural studies, i.e., NMR, but also in X-ray crystallography, mostly using this heavy metal to solve the phase problem in the latter method. The structures of tRNAPhe, RNase P, HIV-1 DIS, and the leadzyme are discussed here in detail. A major part of this review is devoted to the cleavage properties of lead(II) with RNA because of its excellence in catalyzing phosphodiester cleavage. Metal ion binding sites in large naturally occurring ribozymes are regularly determined by Pb2+ cleavage, and also in the in vitro selected socalled leadzyme, this metal ion is the decisive key to backbone cleavage at a specific site. Lead(II) was used in the first in vitro selection that yielded a catalytic DNA, i.e., the DNAzyme named GR5. Next to the GR5, the so-called 8-17E is the second most prominent DNAzyme today. Derivatives of these two lead(II)-dependent DNAzymes, as well as the G-quadruplex forming PS2.M have been applied to detect lead(II) in the lower nanomolar range not only in the test tube but also in body fluids. Due to the toxicity of lead(II) for living beings, this is a highly active research field. Finally, further applications of lead(II)-dependent DNAzymes, e.g., in the construction of nanocomputers, are also discussed.